Author's Accepted Manuscript
Medicinal Plants of the Russian Pharmacopoeia, history and applications
Alexander N. Shikov, Olga N. Pozharitskaya,
Valery G. Makarov, Hildebert Wagner, Rob
Verpoorte, Michael Heinrich
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DOI:
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http://dx.doi.org/10.1016/j.jep.2014.04.007
JEP8734
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Journal of Ethnopharmacology
Received date: 22 January 2014
Revised date: 31 March 2014
Accepted date: 4 April 2014
Cite this article as: Alexander N. Shikov, Olga N. Pozharitskaya, Valery G.
Makarov, Hildebert Wagner, Rob Verpoorte, Michael Heinrich, Medicinal
Plants of the Russian Pharmacopoeia, history and applications, Journal of
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Review
Medicinal Plants of the Russian Pharmacopoeia, history and applications
Alexander N. Shikova*, Olga N. Pozharitskayaa, Valery G. Makarova, Hildebert Wagnerb, Rob
Verpoortec, Michael Heinrichd
a
St-Petersburg Institute of Pharmacy, Bolshaja Porokhovskaja, 56, PoBox 16, 195248, St-
Petersburg, Russia
b
Institute of Pharmacy, Pharmaceutical Biology, Ludwig Maximilian University, D - 81377
Munich, Germany
c
Natural Products Laboratory, IBL, Leiden University, Sylvius Laboratory, PO Box 9505, 2300
RA Leiden, Sylviusweg 72
d
Research Cluster Biodiversity and Medicines. Centre for Pharmacognosy and Phytotherapy,
UCL School of Pharmacy, University of London. m.heinrich@ucl.ac.uk
Correspondence:
Dr. Alexander Shikov
Saint-Petersburg Institute of Pharmacy,
47/5 Piskarevskiy pr.
St.-Petersburg, 195067
Russia
Fax +7-812-3225605
E-mail: spb.pharmacy@gmail.com
1
Abstract
Ethnopharmacological relevance: Due to its location between West and East, Russian
phytotherapy has accumulated and adopted approaches originating in European and Asian
traditional medicine. Phytotherapy is an official and separate branch of medicine in Russia and
thus herbal medicinal preparations are official medicaments. The aim of the present review is to
summarize and critically appraise the data concerning plants used in Russian medicine. This
review describes the history of herbal medicine in Russia, current situation and pharmacological
effects of those specific plants of Russian Pharmacopoeia which are not included in European
Pharmacopoeia.
Materials and methods: Based on the State Pharmacopoeia of the USSR, 11th edition we selected
plant species which have not been adopted yet in Western and Central Europe (e.g. via the
inclusion in the European Pharmacopoeia) and systematically searched the scientific literature
for data through library catalogs, the online service E-library.ru and in addition
Medline/Pubmed, Scopus and Web of Science databases on the species, effectiveness,
pharmacological effects and safety.
Results: The Russian Federation follows the State Pharmacopoeia of the USSR, 11th edition
which contains 83 individual monographs for plants. Fifty one plants are also found in the
European Pharmacopoeia and have been well studied, while 32 plants are only found in the
Pharmacopoeia of USSR. Many articles about these medicinal plants were newer translated in
English and a lot of information collected by Russian scientists was not available for
international community. Such knowledge can be applied in future studies aiming at a safe,
evidence-based use of traditional Russian medicinal plants in European and global
phytopharmacotherapy as well as for the discovery of novel leads for drug development.
Conclusion: The review highlights the therapeutic potential of these Russian
phytopharmaceuticals, but it also highlights cases where concern is raised about the products
safety and tolerability and that would support their safe use.
2
Keywords: Aralia elata, Bergenia crassifolia, Bidens tripartita, Centaurea cyanus, Gnaphalium
uliginosum, Inonotus obliquus, Polemonium caeruleum, Rubia tinctorum, Tussilago farfara
3
1. Introduction
There are estimates that there are about 350,000 higher plants on earth (Heywood 2011).
Relatively speaking, only a very few of the medicinal plants have been studied scientifically.
Russia’s large size, different soils, varied topography and climates favored the growth of an
extensive number of herbs, trees, and other plants. This led to active interest in locally grown
plants, which stimulated serious study by traditional healers and early official physicians alike.
Basically herbal and natural remedies are the product of hundreds of years of careful observation
of their therapeutic effects and risks and that their properties and side effects are quite well
known. In one approach, scientists have isolated one or more of the medicinal principles from a
single herb in the laboratory (and possible enhanced them chemically) to create new medication
that were often more powerful than the original plant. This approach eventually led to the
development of a number of new herb-based medicines as well as to the creation of synthetic
pharmaceuticals that duplicated the active medicinal element in original plant. Aspirin, codeine,
digoxin and other drugs have their origins in herbal medicines (Yarnell, 2000). However, not all
these efforts were successful. Scientists found that the herb itself with its unique combination of
chemical components was often more effective than the chemical derivative along (Li, 2002). As
a result, medical science also focused on the medicinal value of the herb themselves and how
they could best be incorporated into medical practice.
While the science of synthetic medicine moves ahead, the value of medicinal plants and and
especially the highly developed and unique Russian herbal medical tradition are largely
unknown in the West.
Although the information about plants, referred in Russian Pharmacopoeia and its application is
fragmentary. The aim of the present review is to fill this gap by summarizing the data concerning
plants used in Russian officinal medicine. This review describes the history of herbal medicine in
Russia, current situation and pharmacological effects of those specific plants of Russian
Pharmacopoeia which are not included in European Pharmacopoeia. Such knowledge can be
4
applied in the expansion of the use of plants in the pharmacotherapy of European and other
countries as well as for the further discovery of new drugs
2. History of herbal medicine in Russia
In many regions of the world and in a very generic way the use of herbal medicines can be
classfied into two main strands: popular orally transmitted traditions, passed on from generation
to generation, and dogmatic or “official” traditions, which is based more on scientific
investigations (Zevin et al., 1997).
Until the tenth century in Russia the popular healing traditions existed with limited exchange of
ideas between the various regigions, when herbal and medical literature was first introduced. At
this time, copies of a number of Greek herbals found their way into Russia derived from
monastic traditions and were eventually translated into Russian. Unlike herbal practice in other
countries, however, the Russian herbal tradition was strong and well established. The first
pharmacy (potion store) (Rus= ) was opened in Russia in the hospital of KievPechora Lavra in 1005-1010 by the monk Makoveit from Athos – an event which is likely to hav
strengthened the Greek influence on Russian medicie. According to the chronicles of the old city
of Novgorod, Russian herbalists (called "knowledgists") were able to cure infected wounds with
"banya mold" (Solovieva, 2005). In the thirteenth century they discovered the properties of the
mold which was used as bandage on the wound. This predates the development of penicillin in
England by seven centuries. Thus chronicles give good example of level of Russian popular
medicine during this period.
Starting in the mid-thirteenth century and for over three hundred years Russia was occupied by
Tartars and Mongolians. They brought their own herbal traditions, which were incorporated in
healing praxis by local herbalists.
While practically no information is available for the next centuries, during the 15th to the -16th
century the Russian empire expanded. Russia counted among her neighbors countries in Western
Europe and Asia and herbalist started the accumulation and adaptation of herbal traditions of
5
Asian-Arabic herbal system and West European. This led to the development of the unique
features and advantages of the Russian herbal system combining autochtonous and introduced
knowledge and practice.
State-contro over medicine in Russia can be traced back to the end of XVI century. First
enterprise that held responsibility for medical affairs was the Apothecary's Chamber opened in
Moscow in 1581 by Tsar Ivan the Terrible (Ivan Grozny). In 1620 it was reformed to the
Apothecary's Order (Blinova, Yakovlev, 1990). The first head of the Apothecary's Order was
oprichnik (a member of an organization established by Tsar Ivan the Terrible to govern the
division of Russia known as the Oprichnina), Knjaz Afanasy Vjazemsky. Apothecary James
Frencham from Great Britain is generally regarded as the founder of the first Moscow Court
Pharmacy - the progenitor of the Russian medico-apothecary system. The exact date of its
foundation is uncertain but it is likely to be in the years before 1581 (Appleby 1983). The
Moscow Court Pharmacy in Apothecary's Chamber served exclusive needs of the Tsar and his
family (Appleby, 1983).
The first public pharmacy was opened within a public hospital on March 20, 1672 in Moscow.
One of the famous herbalist manuscript "Cool vineyard" (rus=
) was
published in 1672. The main part of manuscript was "About the overseas and Russian potions
and about wood and herbs" (Sokolov, 2000).
In the XVIII century Tsar Peter the Great drove major reforms to the system. One of those
reforms was the Apothecary's Reform that fixed European normative and European type of the
pharmaceutical service. Under a decree by Peter the Great, Korpisaari Island in Saint-Petersburg
was designated in 1714 for Apothecaries' Chancery and principal Pharmacy. And the local
Apothecary's Garden was founded.
Establishing of the State Academy of Science (1724) opened new horizons in systematization of
knowledge and surveys of the rich resources of Russian flora. New medicinal plants were
documented in a four volume work "Flora of Siberia", a result of expedition of I.I. Gmelin in
6
Siberia (1732-1743). After exploration of Siberia and Volga river regions academician P.S.
Pallas published the classical "Description of herbs of Russian State with pictures". Prof. I.I
Lepehin (1740-1802) promoted the utilization of local flora and argued for a reduction of
importing medicinal plants (Muraviova, 1991).
Russia was among the first countries to compile a pharmacopoeia. In 1778 the Pharmacopoea
Rossica was published in St. Petersburg by the Russian Academy of Science. It contains 770
monographs, including 316 of herbal medicinal preparations, 147 chemical substances, 29
medicinal preparations from animal sources and complex mixtures. Each entry is written mostly
in Latin but does give the Russian name of the botanical simple or preparation. Entries for
medicinal plants include their name, geographical origin, odor, taste, therapeutic qualities, uses,
doses, and preparation (Tshibilaev et al., 2006). However, Russia's first National Pharmacopoeia
wirten in Russian was published nearly a century later – in 1866.
In XIX century European physicians had completely forgotten about the herbal traditions that
once predominated in their countries, while Chinese healers had almost no awareness of the
medical developments in the West. Russian doctors were unique because they knew of booth
their own folk-herbal tradition and modern West medicine.
The nineteenth century was marked by the beginning of the study of the chemical composition of
medicinal plants. Starting with the isolation of atropince (1833), in the early 19th century it
became apparent that the pharmaceutical properties of plants are due to specific compounds
which can be isolated and characterized (Heinrich et al 2012). For example, Prof. G.G.
Dragendorf (1879) has published series of articles "Relationship between the chemical
constituents and botanical features of plants" in Pharmaceutical journal.
By the early twentieth century, Russian scientists had generated much scientific data about
medicinal plants. However, in 1917 after the October revolution, the Soviet Union became
closed off from the rest of the world and this research progress was not shared for long time.
Luckily Soviet Union government did not discard Russian medicine and herbalism. Many
7
institutes and academies for the study of medicinal plants were established in all regions of
Soviet Union.
A new era of intensive study of medicinal plants was initiated in the middle of the XX century.
On March 4, 1943, Iosif Stalin have signed Order No 4654-p of the People’s Commissars
Council of the Union of Soviet Socialist Republics "… to study limonnik (Schisandra chinensis
(Turcz.) Baill. (Schisandraceae) with the purpose of finding of tonic substances” for both
soldiers and persons working in the USSR defense industry during the Second World War. In
1945 stimulant effects of Schisandra on nervous muscular excitability in human were published
(Panossian, Wikman, 2008). In result of intensive work of scientists in all parts of big country
the concept of herbal substances as compounds that would increase “the state of non-specific
resistance” under conditions of stress and the term “adaptogens” were formalized between 1947
and 1960. The term adaptogen was introduced in 1947 by N.V. Lazarev while working on a
synthetic compound, dibazol which was found to stimulate nonspecific resistance of organisms
(Lazarev et al., 1959). Later the term ‘adaptogen’ was defined more precisely by famous
herbalists I.I. Brekhman and I.V. Dardymov. Adaptogen must: produce a nonspecific response,
i.e. increase the power of resistance against multiple (physical, chemical or biological) stressors;
have a normalizing effect, irrespective of the nature of the pathology and be non toxic; be
innocuous and not influence normal body functions more than required (Brekhman, Dardymov,
1969; Panossian et al., 1999).
3. Current situation
In results of recent survey, 14% of Russian population use phytopreparations for regular
treatment and 44% time to time (Shikov et al., 2011). Phytotherapy is a separate branch of
medicine in Russia and herbal medicinal preparations (HMP) are official medicaments. Herbal
medicinal preparation is the finished product and pertains to a medical preparation containing
herbal materials and/or herbal preparations as its active ingredients. More than 600 HMP have
8
been registered for medication and included in the Governmental Register of Medicinal
preparation (Register Russia, 2012).
All aspects relating to the development, preclinical and clinical studies, evaluation, state
registration, standardisation and quality control, manufacturing, preparation, storing,
transporting, importing and exporting, advertising, releasing, selling, using, and disposing of
pharmaceutical preparations (including HMP) are regulated by Federal Law No. 61 FZ (dated
12.04.2010) “About circulation of drugs”.
4. Classification of HMP
Depending on the processing method used, the herbal pharmaceutical formulations can be
classified into the following categories (Severtsev et al., 2003):
1. Medicinal plant materials are dried or sometimes newly gathered parts of medicinal plants
(rarely, entire plants) used for the production of medical drugs. Medical species are mixtures of a
few kinds of crushed or integral plant materials with salts and ethers as additives.
2. Summarised non-refined or galenic formulations contain, along with biologically active
substances, a number of related substances. In the course of production, inactive ingredients are
removed from galenic formulations. These include herb infusions and decoctions, tinctures,
extracts, and elixirs.
• Infusions and decoctions are liquid medicinal preparations representing aqueous extracts from
medicinal plant raw materials, as well as aqueous solutions of dried or liquid extractions
(concentrates).
• Tinctures are medicinal formulations in the form of alcoholic and aqueous/alcoholic extracts
from medicinal plant materials (1:5 or 1:10) produced with no heating or removal of extractant.
• Extracts are concentrated extractions from medicinal plant materials in the form of liquid (1:1),
semi solid (moisture < 25%), or dried (moisture < 5%) mass.
9
• Elixirs are liquid medicinal formulations in the form of a transparent mixture of
alcoholic/aqueous extractions from medicinal plant materials with medical drugs, sugars and
flavors as additives.
3. Novo-galenic formulations are phyto-preparations containing a mixture of biologically active
substances that are free from inert and concomitant ingredients. They contain a mixture of
alkaloids, coumarins, etc. Novo-galenic preparations also include such substances as flamine
(dried extract of Helichrysum arenarium L flowers containing flavonoids), ergotal (mixture of
ergot alkaloid phosphates), adonisid (extracted from Coronaria aerial part), etc.
4. Active pharmaceutical ingredients (API) – individual compounds isolated from plants
(serotonin, morphine, rutin, lysergin, etc.). These compounds have direct action and a majority of
them are used for the preparation of injection formulations.
5. Combined phyto-preparations contain, along with the substances extracted from plants,
synthetic, endocrine and other types of ingredients such as "Allokhol" (based on dry extracts
from garlic and nettle with coagulated active coal as additive), "Cholagolum"” (contains extract
of Curcuma longa, emodin from bark of Frangula alni, magnesium salicylate ether oils, oliven
oil and ethanol), "Valocormyde" (based on the tincture of valerian, lily of the valley and
belladonna with sodium bromide and menthol as additives), etc.
5. Information in pharmacopoeia monographs
The Russian Federation follows the State Pharmacopoeia of the USSR, 11th edition. Last issued
in 1987 (part 1) and 1990 (part 2), this Pharmacopeia includes 83 individual monographs for
plants.
Each monograph of the State Pharmacopoeia of the USSR contain information about plant name
(Russian and Latin), plant part, recommended collection time, macroscopic evaluation (for
whole and ground plant material), microscopically observation, quantitative data (loss of drying,
concentration of chemical constituents or biological activity), ash, ash insoluble in 10% HCl,
10
broken parts, organic and mineral adulteration, qualitative assay (chemical reactions or
chromatography), fraction sieve analysis (for grinded material), packaging, storage conditions,
self life, and pharmacological group.
Table 1. approx. here
Different parts of plants are described in the Pharmacopoeia. There are 20 aerial parts (herb), 15
leafs, 14 fruits, 14 roots an rhizome, 8 flowers, 3 bark, 3 seeds, 2 buds, 1 mushroom, 1 cones, 1
alga, 1 columns with stigmas and 1 shoots.
Based on main therapeutic indications there are 13 expectorants, 8 diuretic, 7 astringent, 6 antiinflammatory, 5 bitterness (appetite stimulants), 5 laxative, 3 tonic, 3 cardiotonic, 3 cholinolytic,
3 diaphoretic, 2 cardiovascular, 2 choleretic, 2 haemostatic, 2 antihelmintic, 2 polyvitamin, 2
sedative, 1 antiseptic, 1 ambient, 1 spasmolytic. Three plants have not direct indications in
Pharmacopoeia and in on-line State Register of Medicinal preparations. Just "medicine of natural
origin" is indicated belong to pharmacological application. Eleven plants have not
pharmacological indications in Pharmacopoeia, while its use is claimed in on-line State Register
of Medicinal preparations. Among them 4 are claimed as spasmolytic, 2 haemostatic, one is
expectorant, one hypotensive, one diuretic, one tonic and one metabolism regulator.
About 60 % of plants are referred in European Pharmacopoeia and well studied in Europe, while
32 plants are included in Pharmacopoeia of the USSR only.
In the following we discuss these plants, which are only included in the Pharmacopoeia of the
USSR focusing on their pharmacological effects, data on safety and clinical data.
5.1 Anti-inflammatory
5.1.1. HERBA BIDENTIS
Bidens tripartita L. is an annual plant of Compositae family, 30-100 cm in height with yellow
flowers (common names include threelobe beggarticks, water agrimony and burr marigold). In
11
Russian traditional medicine infusion of aerial part of B. tripartita L. is widely used in the
treatment of catarrhal rhinitis, angina, acute respiratory infection, and as an anti-inflammatory in
colitis, gout, and infantile rickets (Sokolov, 2000). It is also used in oriental medicine as a
diaphoretic and diuretic in nephrolithiasis (Sezik et al. 2004), as antiseptic and for children bath
mainly at diathesis (antiallergic action) (Blinova, Yakovlev, 1990).
The safety was studied in mice. An aqueous-ethanol extract (1:1) of the aerial parts administered
intraperitoneally to mice had a median lethal dose of 750 mg/kg (Bhakuni et al., 1971). No
adverse effects were reported in rats after oral acute administration of B. tripartita at the doses
up to 20 ml/kg of aqueous infusion (1:20) (Pozharitskaya et al., 2010). Table 2 summarizes the
pharmacological studies undertaken on B. tripartita and reported in the literature.
Table 2 approx. here
In an open clinical trial without a control group, a 70% ethanol extract of the aerial parts of the
plant and an ointment containing 2.5% of the extract were administered to 53 patients with
psoriasis. After oral administration of the extract (20 drops three times daily) and simultaneous
application of the ointment to the affected areas of the skin once a day, the combination was
found to have anti-inflammatory activity as well as an ability to stimulate adrenal functions.
After one week of treatment, desquamation of the skin was decreased, and a decoloration of the
psoriatic plaques was observed. A clinical recovery was recorded for 29 of the patients; an
improvement in condition was recorded for 22 patients; and a failure of treatment for 2 patients
(Faraschuk, 1972; Levin et al., 1974).
Bidens tripartita was used in a clinical trial to treat 500 cases of dysentery, 65 cases of acute
enteritis, 248 cases of chronic enteritis. Different forms of the herb were used to make the
medicine for a one day dose, each time, divided into three doses: 200 grams of fresh whole herb
in decoction; three divided doses; 100 grams dried herb in decoction; three divided doses;
granules of aqueous extract, 5 grams each time, three times daily; 0.5 gram tablets of aqueous
extract, 10 tablets each time, three times daily; injection 2 ml each time, 2-3 times daily. The
12
granules and tablets from granules were administered in a total dose of 15 g/day (derived from
about 75 g of dried herb). The herbal materials in various forms were administered for 3-10 days,
and to patients who had already suffered from diarrhea for 7-15 days. In 500 cases of dysentery,
387 cases were reported cured; with 13 not responding in 3 days. In 313 cases of enteritis, all
were cured (12 chronic cases relapsed later). The author of the study pointed out that there had
been an epidemic of dysentery in Shandong Province for many years and that practitioners at
village clinics and the county hospital in Jianan County had used bidens as a remedy for about
10000 patients (Zhang, 1989).
Bidens tripartita is recommended for internal administration at the dose of 1 tablespoon of the
infusion (1:20), 3-4 times a day and one glass of an infusion of 10 g of cut herb together with
100 g of cooking salt or sea salt per bath for external use (Sokolov, 2000).
Bidens tripartita is a popular herb in Russia and its safety and efficacy is confirmed during long
time. The special monograph Herba Bidentis was included in WHO monographs on medicinal
plants commonly used in the Newly Independent States (NIS) in 2010. However there is lack
information in the public literature about efficacy. In revealing more information about bidens,
broad studies can better appreciate the extent of herb application in medicine.
5.2. Diaphoretic, anti-inflammatory
5.2.1. FRUCTUS VIBURNI
Viburnum opulus L. known as guelder rose, water elder, European cranberrybush, cramp bark,
and snowball tree is a deciduous shrub of Caprifoliaceae family growing to 4-5 m tall.
In Russian traditional medicine infusion of fruit has been used for the treatment of hemorrhoids
and fruit juice as laxative and for the treatment of cold either alone or mixed with honey (Utkin,
1931). Berries are recommended as a source of vitamins, tonic and diuretic (Turova and
Sapozhnikova, 1989), hypotensive, choleretic, anti-inflammatory, and sedative in hypertension,
insomnia, convulsions, hysteria (Yelina, 1993). The berries are astringent, therefore, they are
13
seldom consumed directly, but the fruit juice is one of the best known products in the food
market. People living in Middle Anatolia region of Turkey drink juice to prevent some stomach
and kidney problems (Soylak et al., 2002)
The fruits are non toxic (Ehrlen, Eriksson, 1993). The dry fruits of V. opulus are safe at
recommended dose of 65 ml (10 g or fruits in 200 ml) for 3-4 times per day, and available in
pharmacies without a prescription, (Sokolov, 2000). Table 3 summarizes the pharmacological
studies undertaken on V. opulus fruits and reported in the literature.
Table 3 approx. here
No clinical data was found about V. opulus fruits in the available literature. Fruits of V. opulus
are recommended for internal administration at the dose of 1/3 of glass of the infusion (1:20), 3-4
times a day (Sokolov, 2000).
It may be concluded that V. opulus fruits can be regarded as a promising and under-explored fruit
which have been used in food in Europe and Asia, and might find wider applications for
medicinal purposes. However pharmacological effects are not well documented and this subject
is interesting for further study.
5.3. Hypotensive, anti-inflammatory, choleretic
5.3.1. HERBA GNAPHALII ULIGINOSI
The Gnaphalium uliginosum L. (syn Filaginella uliginosa (L.) Opiz), Compositae or Marsh
cudweed is an annual plant widely used in Russian phytotherapy (Blinova, Yakovlev, 1999). In
Russian and Bulgarian phytotherapy it is used in the treatment of hypertension and ulcer
(Buturlin, 1953; Shchepotin et al., 1984; Ivancheva, Stantcheva, 2000). Decoction and infusion
of aerial part of G. uliginosum are known to possess anti-inflammatory, astringent, and antiseptic
properties (Sokolov, 2000). There is some information about application of the herb marsh
cudweed for the treatment of the thrombophlebitis and phlebothrombosis (Turova and
Sapozhnikova, 1989; Shikov et al., 2010). Hypotensive effect of marsh cudweed is associated
14
with decrease of systolic blood pressure because decrease of cardiac output and inhibition of
baroreceptor sensitivity (Turischev, 2008). Oil extracts are used both internally and externally in
the treatment of laryngitis, upper respiratory catarrh and tonsillitis (Gammerman et al., 1984).
According to Voronina (1952) aerial part of the plant is used for treatment of nervous disease.
The aerial part of G. uliginosum was included in the VIII Pharmacopoeia of USSR in 1952.
G. uliginosum herb is generally considered to be safe in infusion at the daily dose of 180-300 ml,
and available in pharmacies without a prescription (Sokolov, 2000). The ethanol (40%) crude
extract did not suppress the growth of human lymphoblastoid Raji cells at concentrations up to
200 g/mL (Spiridonov et al., 2005). Table 4 summarizes the pharmacological studies
undertaken on G. uliginosum and reported in the literature.
Table 4 approx. here
An original method for the treatment of patients with peptic ulcer with a combined
administration of infusions of Polemonium caeruleum and G. uliginosum is reported
(Panchenkov, 1950) and discussed in the part of the article about P. caeruleum. No other clinical
data were found. The aerial part of P. caeruleum is recommended for internal administration at
the dose of 1/2 -1/3 of glass of the infusion (1:20), 2-3 times per day as anti-inflammatory and
hypothensive (Sokolov, 2000).
The safety and efficacy of G. uliginosum is confirmed during long time of application however
publications about chemistry, pharmacological effects and safety are fragmentary. This herb
should be an interesting subject for further investigations.
5.4. Bitterness (appetite stimulants)
5.4.1. HERBA CENTAURII
In the monograph of Pharmacopoeia USSR Herba centaurii described as aerial parts of
Centaurium erythraea Rafn [syn.: C. minus Moench, Erythraea Centaurium (L.) Borkh] and C.
pulchellum (Sw.) Druce, (Centianaceae) collected during the flowering season. In European
15
Pharmacopoeia, C. majus (H. et L.) Zeltner and C. suffruticosum (Griseb.) Ronn. (syn.:
Erythraea centaurium Persoon; C. umbellatum Gilibert; C. minus Gars.) are described
additionally in the monograph Herba centaurii. As soon as pharmacological effects of these
plants are similar it is not reasonable for this review to discuss pharmacological effects of C.
pulchellum.
5.5. Astringent
5.5.1. FRUCTUS ALNI
Fructus alni consist of the catkins of Alnus incana (L.) Moench (grey alder or speckled alder) or
A. glutinosa (L.) Gaertn. (European black alder; Betulaceae), a small to medium size tree 15-20
m tall. Alder catkins are collected late autumn – winter. Decoctions of alder catkins are used in
Russian traditional medicine for the treatment of stomach pain, diarrhea and dysentery (Nosal,
Nosal, 1960).
In 1942 A. incana catkins were introduced in officinal medicine by Prof. D.M. Rossijsky
Rossijsky, 1942; Vereschagin et al., 1959) and dry extract of A. glutinosa catkin Catskin
(themelini) was developed by V.E. Shatadze (Turova and Sapozhnikova, 1989). Due to their s
astringent properties extract was recommended for the treatment of gastrointestinal tract.
Recently it was shown that Fuctus alni has anti-inflammatory, UV- and radioprotective
properties (Sokolov, 2000).
The acute and chronic toxicity of a polyphenolic extract of A. glutinosa Catskin were studied in
rodents after oral administration. The LD50 in acute toxicity study in mice and rats was 5420
mg/kg and 8500 mg/kg respectively. In the chronic toxicity study the extract showed
hepatotoxicity in rats after 6 months administration at the dose of 50 mg/kg, while the
therapeutic recommended dose is 1 mg/kg (Maloshtan, Serbina, 1999). Methanolic extract of A.
incana exhibited very low toxicity and did not cause significant brine shrimp (Artemia salina)
16
mortality even in concentration of 200 g/mL (Stevi et al., 2010). Table 5 summarizes the
pharmacological studies on Fructus alni reported in the literature.
Table 5 approx. here
A group of 50 patients (32 female and 18 male, 19-78 years) suffering from salmonellosis was
included in a clinical trial. Group 1 (25 patients) was treated with drugs therapy (control) and
group 2 was treated with a polyphenole richc extract of A. glutinosa catskin at a dose of 20 mg 3
times per day, during 8 days. The publication did not give a full description of the controls,
which makes that it is difficult to judge the results of this trial. The levels of malonyl-dialdehyde
and lipid conjugated dienes as well as activity of superoxide dismutase in blood serum of the
patients were statistically significant decreased with 33%, 44% and 10% respectively, and were
similar to normal levels in healthy persons. Decrease of malonyl-dialdehyde, lipid conjugated
dienes and superoxide dismutase in group 1 was in 16%, 17% and 30% respectively comparing
to intact level. Based on the results the extract was recommended in the therapy of patients with
salmonellosis (Popova, 2002).
Taking in consideration literature data and application of Fructus alni in the USSR and Russia it
may be considered as safe and effective. Fructus alni is recommended for internal administration
at the dose of 1/2 - 1/3 of glass of the infusion (1:20), 2-3 times a day as astringent (Sokolov,
2000). The tablets "Altan" with 0.01 g of a polyphenolic extract of A. glutinosa catskin are
registered in Ukraine as OTC medicine. Future study of alnus catskin should contribute to wider
medicinal applications.
5.5.2. HERBA HYPERICI
In the monograph of Pharmacopoeia USSR Herba hyperici described as aerial parts of
Hypericum perforatum L., H. maculatum Crantz (syn. H. quadrangulum L.), Hypericaceae
collected during the flowering season. As soon as pharmacological effects of booth plants are
17
similar and H. perforatum is included in European Pharmacopoeia it is not reasonable for this
review to discuss pharmacological effects of H. maculatum.
5.5.3. RHIZOMATA BERGENIAE
Bergenia crassifolia (L.) Fritsch ( Saxifragaceae), commonly known as badan, Siberian tea,
Mongolian tea, leather bergenia, or elephant's ears, is an evergreen perennial plant with rhizomes
up to 1 meter long, 10-50 cm long leather-like large leaves and pink flowers.
Infusions of Bergenia rhizomes have been used in Russian traditional medicine for the treatment
of cold, gastritis, enterocolitis, head-ache, diarrhea and fever (Gammerman et al., 1984). In
Russian ethnomedicine the leaves are widely used as a beverage. Buryats and Mongols are
known to have used B. crassifolia leaves to make tea. However, in Altai old blackened wintered
leaves, known as chagirsky tea, are preferred for this purpose as the green leaves contain higher
amounts of tannins (Vereschagin et al. 1959). In officinal medicine rhizomes are claimed as
haemostatic, astringent, anti-inflammatory and antimicrobial agents. Infusions are recommended
in gynecology for excessive menstruation, bleeding after abortions, and cervical erosion
treatment (Turova and Sapozhnikova, 1989). It is claimed to strengthen capillary walls, to have
local vasodilatation activity, to decrease arterial blood pressure and to increase hearth rate
(Sokolov et al., 2000). Bergenia rhizomes are used for the treatment of oral diseases: periodontal
disease, stomatitis, gingivitis, bleeding gums (Lukomsky, 1955). Bergenia crassifolia is
appearing to meet the criteria of being an adaptogen (Suslov et al., 2002; Panossian, 2003).
Rhizomes of B. crassifolia are safe at the daily dose of 50-100 ml of decoction (1:20), and
available in pharmacies without a prescription (Sokolov, 2000) An infusion of B. crassifolia both
black and fermented leaves (10 g in 100 ml of water) were safe in mice after 7 days of
continuous per-oral administration at the dose of 9 ml/kg (Shikov et al., 2010). At a single oral
dose of 50 mg/kg per day of dry extracts of black and green leaves after one week no signs of
toxicity were observed in the rats (Pozharitskaya et al., 2012). Bergenin and norbergenin, main
18
coumarines of Bergenia, were found to be safe up to 2000 mg/kg weight in mice after per oral
acute administration with no sign of mortality or change in behavioral pattern (Nazir et al.,
2007). The bergenan - pectic polysaccharide from B. crassifolia green leaves was found to be
nontoxic and failed to influence the body weight or the length and weight of intestine (Popov et
al., 2005). The LD50 for sulfated pectin derivatives of B. crassifolia after single intraperitoneal
injection was more than 1000 mg/kg (Vityazev et al., 2012). Table 6 summarizes the
pharmacological studies undertaken on B. crassifolia and reported in the literature.
Table 6 approx. here
In the available literature no clinical data for B. crassifolia were found. Rhizomes of B.
crassifolia are recommended for internal administration at the dose of 1-2 tablespoon of the
decoction (1:20), 3 times per day as astringent, haemostatic, and anti-inflammatory (Sokolov,
2000). Claims for an antimicrobial activity are not supported by the antimicrobial assays, which
only show activity at very high concentrations. Anti-inflammatory activity can be associated
with high concentration of polyphenols, polysaccharides, and -bisabololoxide B (Popov et al.,
2005; Chernetsova et al., 2012; 2014)
It is interesting that black leaves and rhizomes have been used in the traditional medicine, but
rhizomes only are referred to in the Pharmacopoeia USSR. The safety and efficacy of B.
crassifolia both leaves and rhizomes are confirmed during a long period of traditional
application, however publications about chemistry, pharmacological effects and safety are
fragmentary. This plant should be an interesting subject for further investigations especial in
aspect of adaptogenic properties.
5.6. Choleretic
5.6.1. FLORES HELICHRYSI ARENARII
Helichrysum arenarium (L.) Moench also known as dwarf everlast is a perennial plant of
Compositae family, which grows to an average of 15-40 cm tall.
19
The inflorescence of H. arenarium has been used in folk medicine of Russia for its choleretic,
diuretic, anti-inflammatory and detoxifying properties; and applied in the form of infusion for
cystitis, arthritis, rheumatism, gout, for stimulating gastric secretion and for the treatment of
gallbladder disorders (Shass, 1952; Vereschagin et al., 1959). The choleretic, cholagogues,
hepatoprotective and detoxifying activity of the inflorescence of H. arenarium has been known
for a long time in Europe (Kroeber, 1951; Szadowska, 1962; Wagner H, 1993).
The correct administration of H. arenarium (decoction, 1:20, 100 ml 2-3 times per day) or
"Flamin" tablets (purified flavonoids) at therapeutic dose 50 mg 3 times per day during 40 days
is safe. However longer administration may cause development of bile congestion (Sokolov,
2000).
Helichrysi flos has cholagogue and choleretic activity and stimulates the secretion of gastric juice
(Krivenko et al., 1989; Litvinenko et al., 1992). Tablets "Flamin" are used in cases of
cholecystopathy. They affect the chemical composition of bile (increase of cholesterol cholate
coefficient), regulate function of gastrointestinal tract and increase diuresis (Petrovsky et al.,
1953; Skakun, Stepanov, 1988). Table 7 summarizes the pharmacological studies undertaken on
H. arenarium and reported in the literature.
Table 7 approx. here
Increase of bile secretion, reduction of bilirubin and cholesterol levels were observed in patients
with cholecystitis, cholangitis, gallstones and hepatitis treated with H. arenarium. Helichrysum
arenarium prevent the stagnation of bile, improve the metabolic function of the liver, and
decrease the viscosity and relative density of bile. It promotes leaching of sand and small stones
in patients with chronic calculous cholecystitis (Sokolv, 2000). However, no more details are
provided.
Aerial part of H. arenarium is recommended for internal administration at the dose of 1/2of glass
of the decoction (1:20), 2-3 times per day as choleretic. "Flamin" tablets with 0.05 g of
20
flavonoids are recommended for internal administration at the dose 1 tablet 3 times per day
during 10-40 days by patients with cholecystitis (Sokolov, 2000).
The special monograph Flos Helichrysi arenarii was included in WHO monographs on
medicinal plants commonly used in the Newly Independent States (NIS) in 2010. However
publications about chemistry, pharmacological effects are fragmentary and no special publication
about safety. This plant should be an interesting subject for further investigations.
5.7. Antihelmintic and choleretic
5.7.1. FLORES TANACETI
Tanacetum vulgare L., known by the common name of tansy is a flowering herbaceous plant
(Compositae), with finely divided compound leaves and yellow, button-like flowers 50-150 cm
tall.
In Russian traditional medicine tansy has been used to treat intestinal worms (ascaris and
enterobius), diarrhea, digestive problems, as antipyretic and diaphoretic (Nosal, Nosal, 1960).
Tansy has been proposed for use as an insect repellent. Powder of aerial parts caused 100%
paralysis of flies in 15 minutes (Zemlinsky, 1949). It is also mentioned to use in treating hysteria,
migraine, neuralgia, rheumatism, kidney weakness, stomach problems, and fever. Tanacetum
vulgare have antihelminthic, carminative, antispasmodic, stimulant to abdominal viscera, tonic,
emmenagogue, antidiabetic, diuretic and antihypertensive properties. In larger doses, the plant
can induce abortion. Externally, tansy is used as a poultice on swellings, sprains, gout,
contusions, and some eruptive skin diseases and to kill lice and fleas, treats scabies (Abad et al.,
1995; Sokolov, 2000). Tanaceholum®, purified complex extract of flavonoids and
phenolcarbonic acids of tansy flowers (0.05 g/ tablet), is registered in Russia as choleretic,
spasmolytic agent for chronic cholecystitis and biliary dyskinesia (Sokolov, 2000).
The acute and chronic toxic effects of a lyophilized aqueous extract of tansy were studied in
rodents. The no-observed adverse effect levels (NOAEL) of the crude aqueous tansy extract in
21
mice were 7.0 g/kg and 1.0 g/kg, and the lowest-observed adverse effect levels (LOAEL) were
9.0 g/kg and 1.5 g/kg, when given by the oral and intraperitoneal routes, respectively. Mortality
increased with increasing doses, with LD50 of 9.9 g/kg and 2.8 g/kg for the oral and
intraperitoneal modes of administration, respectively. The LD50 was lower for female mice (oral
dose: 8.70 g/kg; intraperitoneal dose: 2.25 g/kg) than for male mice (oral dose: 11.30 g/kg;
intraperitoneal dose: 3.25 g/kg). In the chronic study in rats, daily oral administration of the
crude aqueous extract of tansy up to the dose of 600 mg/kg for 90 days did not result in death or
significant changes in the biological (except for hypoglycemia) and hematological parameters
(Lahlou et al., 2008a).
Safety of Tanaceholum®, was tested on rats, mice, dogs, and guinea pigs. The LD50 was 1.27
g/kg in rats after intraperitoneal administration and 7.42 g/kg in mice after intragastric
administration. It was not toxic and no histopathological effects were detected after 90 days
administration by rats and dogs at the dose of 100 mg/kg. No allergenic effects were fixed in
guinea pigs (Vichkanova et al., 2009). Table 8 summarizes the pharmacological studies
undertaken on T. vulgare and reported in the literature.
Table 8 approx. here
The effect of oral treatment with Tanaceholum® was studied in 291 patients with chronic
cholecystitis. Patients were treated with Taneceholum® tablets (0.05 g) at the dose of 2 tablets 3
times per day in 20-30 min before ingestion during 25 days. The publication did not give a full
description of the controls, which makes it is practically difficult to judge the outcomes of this
trial. The positive effect was registered in 74.9% of patients. The treatment led to a decrease in
bitter taste in the mouth and nausea after 6-7 days, reduced pain in the right upper quadrant after
9-10 days, and dyspepsia disappeared after 15-20 days. No side effects were observed
(Vichkanova et al., 2009).
Flowers of T. vulgare are recommended for internal administration at the dose of 1 table spoon
of the decoction (1:20), 3 times per day as choleretic and antihelmintic. Tanaceholum® tablets
22
with 0.05 g of purified complex extract of flavonoids and phenolcarbonic acids are
recommended for internal administration at the dose 1-2 tablets 3-4 times per day during 20-30
days by patients with biliary system and liver diseases (Sokolov, 2000). However publications
about pharmacological effects and clinical trials are far too limited to allow conclusions about its
therapeutic potential. This botanical drug clearly is an interesting subject for further
investigations especially in a clinical context.
5.8. Expectorants
5.8.1. CORMUS LEDI PALUSTRI
Ledum palustre L. (syn. Rhododendron tomentosum Harmaja), commonly known as marsh
labrador tea, northern labrador tea or wild rosemary, is a low shrub growing to 50 cm (rarely up
to 120 cm) tall with evergreen leaves. It belongs to the family Ericaceae.
In Russian traditional medicine shoots are used in form of aqueous infusion or decoction. The
infusion has been used for treating diverse respiratory and lung disorders including bronchitis,
tuberculosis, (whooping) cough, asthma, for lowering blood pressure, to prevent seizures (Shass,
1952; Vereschagin et. al., 1959), the decoction - as anthelmintic (Utkin, L.A., 1931), the
ointment on the base of animal fats - topically in eczema, scabies, insect stings (Vereschagin et.
al., 1959). In Swedish traditional medicine it has been used for the treatment of headache,
toothache, pain and shingles (Tunón et al., 1995). The leaves are also used as marsh tea, which is
considered to act as abortifacient, diaphoretic, diuretic, emetic, expectorant, and lactagogue (Jin
et al., 1999). In the Norwegian Sami community the decoction of dried "guohcarassi" - "stinking
plant", was considered a good remedy for cold and whooping cough, for rheumatism as pain
reliever, for frost damage of the joints, to lower blood pressure, for bladder catarrh and
diphtheria (Alm, Iversen, 2010). Ledum palustre leaves and shoots are used in China for
treatment of cough, asthma, lowering blood pressure and as antifungal (Li et al., 2002).
23
Ledum palustre is regarded as a poisonous plant due to the content of toxic volatile compounds,
especially the sesquiterpenoid ledol. Ledol can affect the central nervous system, initially leading
to psychomotor stimulation, then to seizures and cramps, finally to paralysis, breathing problems
and even death (Dampc, Luczkiewicz, 2013). As it was suggested, the chronic and extended
exposure to ledol and presumably its overdosage is crucial in causing the serious adverse
reactions, such as dizziness, exhaustion, nausea, vomiting and loss of consciousness (Dampc,
Luczkiewicz, 2013). The essential oil of marsh rosemary applied orally can cause the irritation of
kidneys, urinary tract and the gastrointestinal tract with vomiting and diarrhea (Aronson, 2009;
Habermehl, 1998). However, the only side effects reported for "Ledin", an USSR medicine for
cough, containing 50 mg of ledol in one tablet, recommended total daily dose of 50-100 mg,
divided over 3-5 administrations per day, during 3-10 days, are allergic reactions (Mashkovskii,
2002). The maximal tolerated dose of L. palustre extract in mice after oral administration was
more than 30 g/kg. Extract at doses of 2.5, 5.0 and 10.0 g/kg had no observable genotoxicity in
mice and could inhibit cyclophosphamide, a well known anti-tumor drug, induced genotoxicity
in mice (Jing et al., 2011).
Acute toxicity of 40% EtOH extract and chloroform and hexane fractions of EtOH extract of L.
palustre shoots was studied in mice. The LD50 for 40% EtOH extract was 2800-3200 mg/kg after
intraperitoneal administration and no mortality of mice was observed after intragastric
administration of extract at the dose of 10000 mg/kg. The LD50 for chloroform fraction was 350
mg/kg (intraperitoneal), and 2600 mg/kg (intragastric) and for hexane fraction 420 mg/kg
(intraperitoneal), and 5100 mg/kg (intragastric) respectively (Basova, 2004).
The acute toxicity of ursolic acid extracted from L. palustre was tested in mice. The LD50 after
oral administration was considered as 9.26 g/ kg. The frequencies of micronucleus in mice
administered with high, medium and low doses of the ursolic acid extract were 2.0, 2.0 and 1.8,
respectively. No significant differences in frequency of micronucleus were observed between the
mice administered with the ursolic acid extract and normal mice. The chromosomal aberration
24
rates in the mice administered with high, medium and low doses of the ursolic acid extracts were
1.2%, 1.2% and 1.0%, respectively, and were not significantly different from normal mice. The
results suggest that the ursolic acid extract from L. palustre is safe with low acute toxicity but
without genetic toxicity (Jing et al., 2009).
Pharmacological properties of L. palustre shoots depend on the essential oil, which after
intragastric administration partially are excreted through the mucous membranes of the
respiratory system. Volatile compounds of L. palustre eliminated through the bronchi, have a
moderate effect on the local irritating mucous membranes, increase secretion of bronchial glands
and increase the activity of ciliated airway epithelium. Spasmolytic effect of L. palustre on
airway smooth muscle was observed (Sokolov 2000). It has been reported that the expectorant
and antitussive effect of L. palustre is caused by ledol (Belousov et al., 1998). Table 9
summarizes the pharmacological studies undertaken on L. palustre and reported in the literature.
Table 9 approx. here
The traditional applications of shoots of L. palustre in different countries are mostly for cough,
bronchitis, lung disorders, and lowering blood pressure. Effects and safety of L. palustre has
been demonstrated in number of experiments and it is recommended in Russian officinal
medicine as an effective expectorant for the treatment of bronchitis and other lung diseases
accompanied with cough in form of infusion (1:20) at the dose of ¼ of glass, 2-3 times per day
(Sokolov, 2000). The film-coated tablets “Ledin” (contain 50 mg of ledol) are recommended for
acute and chronic bronchitis, pneumonia and bronchitis caused by chemicals, gases, fumes and
vapors, asthma, pulmonary tuberculosis, cystic fibrosis and frequent, mostly dry cough with the
dose of 1-2 tablets3–5 times a day during 3-10 days (Mashkovskii, 2002). However, additional
study about safety (especial chronic toxicity) and efficacy are needed.
25
5.8.2. FOLIA FARFARAE
Tussilago farfara L. (Compositae) commonly known as coltsfoot, is a perennial herbaceous
species of 10 - 30 cm in height. The traditional use of leaves of T. farfara in Russia is to treat
respiratory illnesses such as asthma, bronchitis, or the common cold as expectorant and sedative.
Additional uses include the improvement of digestion, treatment of diarrhea, topical application
for furunculosis and as analgesic (Vereschagin et al., 1959). The leaves are components of
pectoral and diaphoretic teas (Gammerman et al., 1984). In China the dried flower buds of T.
farfara are used to treat cough, bronchitis and asthmatic conditions (Committee for the
Pharmacopoeia of People’s Republic of China, 2010).
There is extensive discussion in the literature about the safety of T. farfara. Besides acidic
polysaccharides, which are considered to be responsible for the cough relieving effect (Franz,
1969), T. farfara contains (generally comparatively low levels) pyrrolizidine alkaloids, which are
known to be liver toxic. The main alkaloid is senkirkine with traces of senecionine. The content
of senkirkine in samples of T. farfara flowers was found to vary from 19.5 ppm to 46.6 ppm
(Jiang et al., 2009). The concentration of senkirkine in commercial samples of coltsfoot leaves
was 2.5-11.2 ppm as determined by capillary zone electrophoresis after different methods of
extraction. Senecionine in leaves was either below the detection limit (by gas chromatography)
or present in less than 0.9 ppm when measured by capillary zone electrophoresis (Lebada et al.,
2000).
A small lifetime study of rats fed 32% young, pre-blooming flowers of coltsfoot in their diet for
4 days, and subsequently 16% diet until the 380 days was performed. All the rats survived
beyond 380 days after the start of feeding, but 8 out of 12 rats developed hemangio-endothelial
sarcoma in the liver (Hirono et al., 1976). In the absence of epidemiological data, the
International Agency for Research on Cancer listed senkirkine as an agent not classifiable as
carcinogenic to humans (Group3) (Barceloux, 2008).
26
Roulet et al. (1988) have reported on a case of a newborn female infant from Switzerland with
fatal hepatic vaso-occlusive disease. Her mother revealed the occasional consumption of
cannabis and hallucinogenic mushrooms some months before the actual pregnancy, and the daily
consumption of a single cup of the herbal tea represenings a toxic amount of senecionine (0.60
mg/kg dry weight) during her entire pregnancy. The exact composition of the incriminated cough
tea was obtained from the manufacturer; of the 10 different plants in this preparation, leaves of
T. farfara made up 9% (w/w). In a comment responding to this article, Röder assumed that the
herb containing pyrrolizidine alkaloids was not tussilago but petasites, because the typical
leading alkaloid of Tussilago, senkirkine, was not found by the authors (Röder, 1988). He argued
that leaves of petasites had most probably been confused with Tussilago because both plants
grow wild in alpine regions and can be easily confused when gathered after the blossom period.
The result of the future research showed that the cough tea, contrary to the presentation in the
publication of Roulet, contained not only leaves and flowers of T. farfara but also roots of
Petasites hybridus (L.) G.Gaertn., B.Mey. & Scherb. (discussed as Petasites officinalis Moench)
(Spang, 1989)). The next report concerned an 18-month-old boy from the Southern Tyrol with
reversible hepatic Veno-occlusive disease as a result of over 15 months consumption of herbal
tea which contained large amounts of seneciphylline (about 60 g/kg body weight per day) was
published in 1995. Leaves from Adenostyles alliariae (Alpendost) were mistakenly taken for T.
farfara (coltsfoot) by parents. Also these two plants can easily be confused especially after the
flowering period. The child was given conservative treatment only and recovered completely
within 2 months (Sperl et al., 1995). Both clinical cases were because of adulteration of coltsfoot
with other more toxic plants.
However, in order to avoid any risks for consumers, the German public health authorities
(Bundesgesundheitsamt, 1992) limited the daily intake of toxic pyrrolizidine alkaloids to 1 g.
Intravenous injection of the alcoholic extracts or decoctions of T. farfara to cats induced a
primary depression effect which was followed by a more rapid acute rise in mean blood pressure
27
and finally a sustained pressor response for several minutes. No tachyphylaxis was observed.
The blood pressure response was associated with increases of heart rate and respiratory
stimulation. It was suggested that the mechanism of action of Tussilago on blood pressure may
be due to stimulation of the vasomotor center of medulla, and the vascular -receptor and
constriction of the peripheral blood vessels (Wang, 1979). Significant antimutagenic activity of
juice prepared from fresh leaves of T. farfara in dilution 1:10 and 1:100 was observed against
genotoxic nalidixic acid in SOS chromotest (Karamova et al., 2010). Water-soluble
polysaccharides of coltsfoot reduce the toxic effect of paclitaxel on the blood system in mice
with Lewis lung carcinoma (Safonova et al., 2010). Table 10 summarizes the pharmacological
studies undertaken on T. farfara and reported in the literature.
Table 10 approx. here
The efficacy of mixtures with T. farfara was been shown in the complex treatment of
rhinosinusitis in miners with chronic bronchitis (Lavrenov et al., 1988). But no details are
provided by author.
The leaves of T. farfara are used in Russian traditional medicine and were included in the VIII
Pharmacopoeia of USSR in 1952. Since this time no adverse effects or toxicity were reported in
Russian publications. Taking into account the long history of application in traditional medicine
infusion of T. farfara leaves (5 g in 300 ml of water) can be considered as a safe medicine at the
recommended therapeutical dose of 1/2-1/3 of a glass 2-3 times per day as expectorant (Sokolov,
2000). The possibilities of adulterations must, however, be carefully monitored (Roulet et al.
1988, Sperl et al. 1995). Publications about chemistry and pharmacological effects are
fragmentary. This plant should be an interesting subject for further studies.
5.8.3. FOLIA PLANTAGINIS MAJORIS
Plantago major L. is a perennial plant that belongs to the family Plantaginaceae. The leaves of
P. major have long been used in Russia for wound healing and as expectorant, antiphlogistic,
28
pain-relieving herb (Turova and Sapozhnikova, 1989; Sokolov, 2000). Whole or fragmented,
dried leaves and scape of Plantago lanceolata L. are approved by European Pharmacopoeia.
As soon as pharmacological effects of booth plants are similar it is not reasonable for this review
to discuss pharmacological effects of P. major.
5.8.4. GEMMAE PINI
Gemmae pini consist of the buds of Pinus silvestris L., of Pinaceae family collected early spring.
The pine buds are widely used in Russian traditional medicine as expectorant, slightly diuretic,
in the treatment of chronic bronchitis and tuberculosis. It can be used for aromatic
baths that improve skin condition and supportive treatment of arthritis (Vereschagin et. al., 1959;
Gammerman et al., 1984).
Pine buds are safe, available without a prescription, and recommended for decoction (10 g of
buds in 200 ml of water) or inhalation. The decoction is used at the dose of 60-100 ml 2-3 times
per day as expectorant (Sokolov, 2000). Buds are used as raw material for steam distillation of
essential oil. The Pini sylvestris aetheroleum is included in European Pharmacopoeia. Therefore
we don't discuss pharmacological profile of oil.
5.8.5. RHIZOMATA ET RADICES INULAE
Elecampane (Inula helenium L.), also called horse-heal, is a perennial composite plant from 90
cm to 150 cm high, belonging to Compositae family. In Russia roots of elecampane are used as
an expectorant in chronic respiratory diseases: bronchitis, tracheitis, tuberculosis and bronchitis
with lots of mucus (Turova and Sapozhnikova, 1989). A decoction made from elecampane roots
is often prescribed as an antiphlogistic and haemostatic for treating problems of the
gastrointestinal tract. It increases stomach and intestinal secretion thus stimulating the appetite
and improving digestion (Zevin et al., 1997). Preparations of its roots are used in the folk
29
medicine of several ethnic groups against a variety of ailments including asthma, (whooping)
cough, bronchitis, lung disorders, tuberculosis, indigestion, chronic enterogastritis, infectious and
helminthic diseases (List and Hörhammer, 1976; Cantrell et al., 1999; Huo et al., 2008).
The safety of elecampane was evaluated in mice, rats, rabbits and other animals. The LD50 of
infusion, tincture, liquid extracts of I. helenium roots was over 5000 mg/g booth in mice and rats.
Median lethal dose of tincture was 14043 mg/kg for mice and 12684 mg/kg for rats. Median
lethal dose of liquid extract was 13230 mg/kg for mice and 12285 mg/kg for rats (Gurskaya et
al., 2009a). Safety of I. helenium infusion, tincture, liquid and dry extracts was evaluated in
irritating tests on guinea pigs, rabbits, sheep and piglets. There was no irritating effect after
transdermal application of all forms of I. helenium. Irritating activity of infusion after application
to eye conjunctiva was evaluated as light, while the effect of dry extract (10-20% suspension in
water) was estimated as a limited one, which disappeared in 24 hours. Irritating activity of
tincture and liquid extract (70% ethanol) was evaluated as a pronounced one, which did not
disappear in 24 hours (Gurskaya et al., 2009b). Table 11 summarizes the pharmacological
studies undertaken on I. helenium as reported in the literature.
Table 11 approx. here
A clinically tested and approved extract of I. helenium root (standardized by the sum of
sesquiterpene lactones), which is marketed in Russia under name "Alanton" (since 1979), is
prescribed for the treatment of acute and chronic infectious and inflammatory diseases of the
respiratory system, accompanied by a persistent cough with thick viscous mucus, to stimulate
blood circulation in the stomach and to accelerate the healing of stomach ulcers (Mashkovskii,
2002). In an open clinical trial without a control group, "Alanton" tablets were administered to
24 patients with peptic ulcer. After oral administration of the tablets (0.1 g three times daily
during 3 weeks), a clinical recovery was recorded for all of the patients. The level of protein in
blood serum, primarily due to albumin and -globulins was increased. The decrease of pyrosis,
nausea, and vomiting were registered on 7-10 days, appetite of patients was improved and body
30
weight was increased in approximately 3 kg. The treatment was resulted in regeneration of
gastric epithelium and decrease of ulcer size. It was concluded that "Alanton" have antiinflammatory activity, contributes to the mucus production and mucus membrane regeneration
(Luchkova, 1978).
Roots of I. helenium are recommended for internal administration at the dose of ½ glass of the
decoction (16:200), 2-3 times per day as expectorant at the upper respiratory tract infections.
"Alanton" tablets with 0.1 g of the sum of sesquiterpene lactones are recommended for internal
administration at the dose 1 tablet 3 times per day during 6-8 weeks by patients with inflamed or
scarred stomach ulcer (Sokolov, 2000). The extracts and isolated compounds of I. helenium have
been determined to have interesting biological activities, suggesting that Radix Inulae could be a
lead to develop further potential drugs.
5.8.6. RHIZOMATA CUM RADICIBUS POLEMONII
Polemonium caeruleum L., (Jacob's ladder or Greek valerian; Polemoniaceae) is a hardy
perennial flowering plant a height about 35-140 centimeters and has been used in Russian
traditional medicine as sedative similar to valerian, tuberculosis, and whooping cough. In
Ukraine it was used for childrens bath. The infusion of the roots drinks in fever (Turova and
Sapozhnikova, 1989, Sokolov, 1990). In modern medicine it is recommended as expectorant for
bronchitis, neurosis, and stomach and intestinal ulcers in combination with Gnaphalium
uliginosum L. (Mashkovskii, 2002).
Varlakov first studied this plant in 1932 in connection with the medicinal flora of Eastern Sayan.
He proposed it as an expectorant to replace imported Polygala senega L. (Varlakov, 1943). It
was shown in experiments on rabbits with cholesterol induced atherosclerosis that saponins of P.
caeruleum have a hypocholesterolemic effect, decrease development of atherosclerosis and
reduce lipid levels in skin, aorta and liver (Sokolov, 1990). The Rhizomata cum Radicibus
31
Polemoni were included in the State Pharmacopoeia of USSR in 1961 (Maltseva and Sorokina,
2010) and a limited number of pharmacological studies are available (Table 12).
Table 12 approx. here
No toxicity was observed after treatment of patients with 45 mL of infusion of P. caeruleum (6g
of roots in 200 mL of water) a day during two weeks, but because some irritating effect it should
be taken after a meal (Panchenkov, 1950; Turova and Sapozhnikova, 1989).
In an open clinical trial without a control group, a group of patients with tuberculosis, acute and
chronic bronchitis and lung abscess was treated with 0.75 mL of P. caeruleum liquid extract, to
be taken 3 times a day, and 45-75 mL of infusion (6 g of roots in 200 mL of water) for 30 days.
The therapeutic effects were observed in 60% of the patients, but no clear scale for primary
outcome parameters seem to have been defined. Treatment of patients resulted in increased
phlegm and facilitation of its evacuation. Catarrhal conditions of the lungs were improved with
the result that cough diminishes (Turova, 1955). Another group of patients with psychiatric
disorders was treated with 15 mL of infusion of P. caeruleum (6g of roots in 200 mL of water) to
be taken three time a day after a meal for a 2 weeks period. Sedative effect was observed in all
patients (Turova and Sapozhnikova, 1989), but details are lacking.
A specific method for the treatment of patients with peptic ulcer with a combined administration
of infusions of P. caeruleum and G. uliginosum was reported. The rationality of this therapy is
due to a sedative effect of P. caeruleum and a local effect of G. uliginosum that accelerates ulcer
healing. Seventy patients with ulcers were treated with 15 mL of infusion of P. caeruleum (6 g of
roots in 200 mL of water) and 50 mL of infusion of G. uliginosum (10 g in 200 mL of water) to
be taken three times a day after a meal for 2 weeks period. No side effects were observed. Most
of patients showed diminished gastric pain and less blood in the stool. Based on radiographic
examination the gastric ulcer lesions (called ‘niches’) disappeared and the gastric pH was usually
normalized. Treatment of patients with only one of the infusions was not effective (Panchenkov,
1950).
32
Roots and rhizomes of P. caeruleum are recommended for internal administration at the dose of
1 table spoon of infusion (6:200), 3-5 times per day as expectorant, and at the dose of 1 table
spoon 3 times per day together with an infusion of the aerial part of G. uliginosum as antiinflammatory agent in case of stomach ulcer (Sokolov, 2000). Polemonium caeruleum has been
used clinically for a long time, roots and rhizomes are OTC. However, the chemical and
pharmacological evidence to support the medical applications especially as expectorant is from
the early 50th of last century and needs further confirmation.
5.9. Diuretics
5.9.1. CORTEX VIBURNI
Viburnum opulus L. (Adoxaceae) known as guelder rose, water elder, European cranberrybush,
cramp bark, and snowball tree is a deciduous shrub growing to 4-5 m high.
Infusion of bark is used in Russian traditional medicine in the treatment of scrofula in children,
asphyxia, cold, uterine, gastric and hemorrhoidal bleeding (Vereschagin et al. 1959). The bark
has been used to treat high blood pressure, heart troubles, tuberculosis, shortness of breath,
stomach pain, digestive troubles, duodenal ulcers and bleedings, kidney and bladder affections,
coughs and colds, has astringent activity (Smirnova, Iadrova, 1968, Velioglu et al., 2006,
Zayachkivska et al., 2006; Sokolov, 2000). The tannins of V. opulus bark bind the mucous
proteins after intragastric administration, causing them to precipitate and to cover and protect the
sensitive stomach cells. As a consequence, the local pain is decreased, vessels are contracted,
secretion of gastric juice is decreased and membranes density is increased resulting in a
reduction of the inflammatory reaction. In 1952 the bark was included in the State
Pharmacopoeia of the USSR (Vereschagin et al. 1959).
In the available literature there is no data about toxic effects of V. opulus bark. The bark of V.
opulus is available without a prescription in pharmacies in Russia and safe in decoctions form at
33
the dose of 18-36 ml 3-4 times per day (Sokolov, 2000). Table 13 summarizes the
pharmacological studies undertaken on V. opulus bark and reported in the literature.
Table 13 approx. here
In the literature found no clinical data are reported. Bark of V. opulus is recommended for
internal administration at the dose of 1-2 table spoon of the decoction (1:20), 3-4 times per day
as diuretic and antiseptic. It has been used clinically for a long time as OTC. However, the
information about chemical and pharmacological effects is not enough and the bark should be
studied in more detail.
5.9.2. FLORES CENTAUREAE CYANI
Centaurea cyanus L. also called blue cornflower or bachelor’s button is an annual plant of
Compositae family, with grey-green branched stems. Flowers are used in Russian traditional
medicine as a diuretic, for the treatment of cystitis, cough, nervous and gastric diseases, uterine
bleeding, in children against diarrhea and for eye’s washing (Vereschagin et al., 1959). Flowerheads are a well-known crude drug used in European traditional medicine in the treatment of
minor ocular inflammation (Bruneton, 1995), fever, gynecological problems, digestive
complaints (Kern et al., 1972; Hansel et al., 1992), wounds and dermatological complaints
(Pieroni et al., 2004). Dried flowers of C. cyanus are used to relieve diarrhea, gain energy,
increase appetite, and to relieve chest tightness (Arif et al., 2004). Centaurea cyanus is
recommended as component of herbal mixtures for the treatment of edema associated with
kidney diseases, as well as diseases of the urinary tract (nephritis, cystitis, urethritis), diseases of
the liver and biliary tract (Turova, Sapozhnikova, 1989).
There is no data about toxic effects of C. cyanus available in the literature. In a recently
published review of retrospective observational case reports of ocular side effects or systemic
side effects from medications used for the eye from herbal medicines and nutritional
supplements Fraunfelder (2004) has mentioned that cornflower is used for the treatment of
34
conjunctivitis and ophthalmia. No side effects for C. cyanus were found in the reports submitted
to the WHO, the Food and Drug Administration, and the National Registry of Drug- Induced
Ocular Side Effects (Fraunfelder, 2004). The dry flowers of C. cyanus are available without a
prescription in pharmacies in Russia and safe in decoctions at the dose of 18 ml 3 times a day
(Sokolov, 2000). Only a limited number of pharmacological studies of C. cyanus are available
and these are summarized in Table 14.
Table 14 approx. here
No clinical data were found about C. cyanus. Flower-heads of C. cyanus are recommended for
internal administration at the dose of 1 table spoon of infusion (1:20), 3 times per day as diuretic.
It has been used clinically for a long time as OTC. However, the information about chemical and
pharmacological effects is limited and this subject is interesting for further study.
5.9.3. FOLIA VITIS-IDAEA
Vaccinium vitis-idaea L., (lingonberry, or cowberry, Ericaceae) is a short evergreen shrub up to
25 cm tall, with leathery evergreen leaves. In Russian traditional medicine infusions or
decoctions from leaves have been used as an astringent and diuretic for leaching of kidney
stones, in cases of stomach pain, diarrhoea, and rheumatism (Vereschagin et al., 1959; Nosal,
Nosal, 1960). Vaccinium vitis-idaea leaves are used as an anti-inflammatory medicine in China
in order to treat respiratory system infections (Wang et al., 2005). Decoction of V. vitis-idaea
leaves is recommended in modern medicine in Russia as diuretic, cholagogue, antiseptic and
astringent for the treatment of kidney and bladder diseases, gastroenteritis, diarrhea, as well as in
case of rheumatism, gout and arthritis (Sokolov, 2000). The leaves of V. vitis-idaea were
included in the VIII Pharmacopoeia of the USSR in 1952.
In the literature there is no data on toxic effects of V. vitis-idaea leaves. The acute toxicity of
polyherbal mixture "Brusniver" which contains 50% V. vitis-idaea leaves, 20% Hypericum
perforatum L. (Hypericaceae) aerial part, 20% Rosa spp. L (Rosaceae) pseudo fruits and 10%
35
Bidens tripartita L (Compositae) aerial part was studied in mice. Concerning acute toxicity the
intragastric administration of the infusion was found to be safe as no mortality of mice was
observed after administration of the extract at the dose of 30 g/kg (equivalents of dry mixture),
and LD50 was not reached. No toxicity signs were observed in female rats after intragastric
administration of the infusion (20 and 40%) of the mixture at the doses up to 8 g/kg during 21
days (Vichkanova et al., 2004). Table 15 summarizes the pharmacological studies undertaken on
V. vitis-idaea as reported in the literature.
Table 15 approx. here
The effect of an oral treatment with "Brusniver" infusion (200 ml/day, during 14 days) was
studied in 31 patients with pyelonephritis, urolithiasis and urethritis. The publication did not give
a full description of the controls, which makes it difficult to judge the outcomes of this trial. The
positive effect was registered in 83.8% of patients, but it seems that no clear primary outcome
parameters were defined. All patients well tolerated the treatment and no side effects were
observed (Vichkanova et al., 2004).
Leaves of V. vitis-idaea are available in Russia in pharmacies as OTC and recommended for
internal use at a dose of 1/2 - 1/3 glass of the decoction (6:200), 2-3 times per day as diuretic,
cholagogue and antiseptic (Sokolov, 2000). However, the information about chemical and
pharmacological effects is insufficient and this is of interest for further study.
5.9.4. GEMMAE BETULAE
Gemmae betulae consist of the buds of Betula pendula Roth and B. pubescens Ehrh.
(Betulaceae). The birch buds are widely used in Russian traditional medicine as diuretic,
expectorant, cholagogue, diaphoretic, blood-purifying, analgesic, anti-infective and antiseptic for
wound healing, furunculosis and as a wash to remove skin spots (Vereschagin et al., 1959;
Nosal, Nosal, 1960; Zevin et al., 1997). Infusions and decoctions of birch buds are used in
stomatology and otolaryngology as anti-inflammatory, for stomatitis, gingivitis, periodontitis,
36
glossitis, sore throat, chronic tonsillitis, acute respiratory diseases as a rinse and application of
gauze pads, moistened with infusions or decoctions (Lavrenova and Lavrenov, 1997).
The use of birch buds since centuries, in adequate doses, presents no toxicity or contraindications
except ingestion because of ether oils of buds. However, we have not found the data about toxic
effects of Gemmae betulae in the available literature. Table 16 summarizes the pharmacological
studies undertaken on Gemmae betulae as reported in the literature.
Table 16 approx. here
A group of 108 patients with purulent wounds (83 had superficial wounds, 10-deep wounds, 15cavitary wounds) was treated with 20% tincture of birch buds in 70% EtOH. The publication did
not give a full description of the controls, which makes it is practically difficult to judge the
outcomes of this trial. Positive results were obtained after using the birch buds tincture in all the
patients, including patients with antibiotic-resistant microbial flora, but it seems that no clear
primary outcome parameters were defined (Zakharov et al., 1980). Birch buds have been used in
the patients with the edema of cardiac origin as a diuretic. A significant increase in diuresis
(urine) and a sharp decrease in edema were observed. However in case of functional kidney
failure, this type of treatment is not recommended because of possible irritation of the renal
tissue with resinous substances (Sokolov, 2000).
A beneficial effect of birch buds was shown in the treatment of patients with acute and chronic
forms of eczema (Pevzner, Raitsina, 1954).
Birch buds are available in Russia pharmacies as OTC and recommended for internal
administration at the dose of 1/2 - 1/3 glass of the infusion (1:20), 2-3 times per day as diuretic
and cholagogue (Sokolov, 2000). However, the information about chemical composition and
pharmacological effects is insufficient and this is of interest for further study.
37
5.10. Cardiotonic
5.10.1. HERBA ADONIDIS VERNALIS
Adonis vernalis L., known as, among others, pheasant's eye, spring pheasant's eye, yellow
pheasant's eye and false hellebore, is a perennial flowering plant of the family Ranunculaceae. It
is included in German Homoeopathic Pharmacopoeia.
Traditionally, in Siberia a water infusion of the aerial parts has been used against malaria,
edema, cardiac edema and several other heart-related problems, kidney diseases (Utkin, 1931;
Nosal, Nosal, 1960). In 1879 alcoholic extracts of A. vernalis were first introduced into medicine
by the Russian medical doctor N.O. Bubnow, who employed them as a cardiac stimulant (Heyl
et al., 1918). In 1898 the famous Russian neurologist Vladimir Bekhterev suggested a mixture of
A. vernalis with sodium bromide (or potassium bromide) or codeine for the treatment of light
forms of heart failure, panic disorder, dystonia, and epilepsy (Bekhterev, 1898). The biological
activity of the A. vernalis aerial parts (1:20 EtOH 95% extract) was defined as 50-66 frog units
or 6.3-8.0 cat units according to the State Pharmacopoeia of the USSR 11th ed.
The toxicity of A. vernalis leaves was assayed by the one-hour frog method which is official for
tinctures of digitalis, strophanthus, and squill. The average minimum dose producing a
permanent systole (M.S.D.) of the frog’s ventricle at the end of exactly one hour for the tincture
of A. vernalis (1:10, 95% alcohol) was 0.0045 ml/g frog. (Heyl et al., 1918). The LD50 of
cymarin (one of active glycoside) after intravenous injection in rats was 24.8±1.8 mg/kg (Vogel,
Kluge, 1961) and intravenous injection in cats was 95.4±3.0 g/kg (Chen et al., 1942). The
M.S.D. for adonitoxin and cymarin are 0.621±0.046 g/g and 0.880±0070 g/g frog respectively
(Chen, Anderson, 1947). The LD for adonitoxin after intravenous injection in cats was
191.3±17.5 g/kg (Chen, Anderson, 1947).
The preparation of Adonis slows, regulates and strengthens heart contractions, increase blood
pressure and has a mild diuretic action. It reduces dyspnea and relaxes smooth muscle in the
lungs allowing deeper breathing. It is especially indicated in congestive heart failure with
38
arrhythmia, feeble force of contractions with dyspnea and dropsy. In case of heart failure,
accompanied by cardiac conduction disturbance, Adonis can be as effective as Digitalis, however
it is not cumulative and doesn’t cause the phenomenon of a heart block as Digitalis (Turova and
Sapozhnikova, 1989). Table 17 summarizes the pharmacological studies undertaken on A.
vernalis as reported in the literature.
Table 17 approx. here
In first half of XXth century pharmacological effects of A. vernalis were studied extensively in
Russia but the literature from that time is poorly accessible. The novo-galenic preparation
"Adonisid" (specific extract of A. vernalis) was produced in USSR in form of tablets, but
nowadays it is excluded from the State Register of drugs. "Adonisid" is used in modern medicine
as a part of the complex phytomedicine "Cardiovalen" (consist of 17.2 mL of pressed juice of
Erysimum diffusum Ehrh. (Brassicaceae), 30.3 ml of "Adonisid" with 85 frog units in 1 mL, 48.6
mL of tincture of Valeriana officinalis L. (Valerianaceae), 2.2 mL of liquid extract of Crataegus,
0.4 g of camphor, and 2 g of NaBr).
Aerial part of A. vernalis is prescribed in Russia for internal use at a dose of 1 table spoon of the
infusion (7:200), 3-5 times per day as cardiotonic. "Cardiovalen" is prescribed at a dose of 15-20
drops, 1-2 times per day (Sokolov, 2000).
5.10.2. HERBA CONVALLARIAE et FOLIA CONVALLARIAE et FLORES
CONVALLARIAE
In terms of the Pharmacopoeia of the USSR, Herba Convallariae, Folia Convallariae and Flores
Convallariae consists of the whole or cut dried aerial part, leaves or flowers of Convallaria
majalis L. (syn: C. transcaucasica Utkin ex Grossh.), C. keiskei Miq. (Asparagaceae),
respectively, which are harvested during the flowering period or its beginning (for leaves).
Depending on the region the harvesting time can be shifted to obtain high quality raw plant
material. Particularly in the St-Petersburg region optimal harvesting time for Herba Convallariae
39
is the late budding and early flowering stage (Borisova et al., 1984). Convallaria majalis is
commonly known as the lily of the valley and has been recognized by clinicians to have an
antiarrhythmic effect. Felter found it particularly useful for treating tachycardia and mitral
insufficiency. He found it less useful for addressing aortic valve problems (Felter, 1922). Unlike
the much stronger and more dangerous Digitalis spp., lily of the valley glycosides do not
accumulate and are safer and produce milder effects (Yarnell, Abascal, 2003). The flavonoids of
C. majalis are also considered to be important for the activity of the botanical drug and this
supports the use of the whole plant and not just the cardiac glycosides in isolation (Weiss, 1988).
Flowers of C. majalis have been used in Russian traditional medicine for the treatment of
epilepsy, cardiac dropsy and for people with mild congestive heart failure (Nosal, Nosal, 1960;
Gammerman et al., 1984). According to the State Pharmacopoeia of the USSR 11th ed, the
biological activity of C. majalis should be at least 120 frog units or 20 cat units for aerial part
(1:20 EtOH 95% extract), 200 frog units or 33 cat units for flowers (1:20 EtOH 95% extract) and
90 frog units or 15 cat units for leaves (1:20 EtOH 95% extract).
Convallaria majalis has been reported to be toxic owing to its content of cardioactive glycosides
convallarin and convallamarin. The LD50 for convallarin in rabbits after intravenous
administration was 1500 g/kg (Marhold, 1986). Lowest published lethal dose for convallarin in
rabbits after subcutaneous administration was 10 mg/kg, in frogs after oral administration 200
mg/kg and after subcutaneous administration - 15 mg/kg (Abderhalden, 1935). The LD50 for
convallarin in rabbits after oral administration was 320 mg/kg (Marhold, 1986). Table 18
summarizes the pharmacological studies undertaken on Convallaria as reported in the literature.
Table 18 approx. here
The novo-galenic preparation "Corglycon" (0.06% aqueous solution of purified total glycosides
from C. majalis leaves) was developed in Ukraine SSR during the Soviet period. It is clinically
approved and standardized to 11-16 frog units, or 1.8-2.2 cat units per 1 mL. The
pharmacological effect of "Corglycon" is similar to that of strophanthin, but more prolonged. It
40
is prescribed for patients with acute and chronic class II and III heart failure, cardiac
decompensation, for cupping of paroxysmal tachycardia (Mashkovskii, 2002).
A group of 34 patients having stage II-III atherosclerotic dyscirculatory encephalopathy with
coexisting ischemic heart disease in the presence of stenosing and occlusive lesions of major
brain arteries were evaluated for effects pentoxiphyllin and corglycon on the clinical course of
this medical condition as well as systemic and cerebral haemodynamics. In this series, 82.7 % of
patients derived benefit from a single intravenous infusion of pentoxiphyllin and corglycon and
course treatment with this drug preparation showed an improvement in the parameters of
systemic and cerebral hemodynamics and regression of neurologic symptomatology. The results
of these studies were the basis for recommending pentoxiphyllin in combination with corglycon
for treatment of patients with eukinetic and hypokinetic type systemic haemodynamics, whereas
pentoxiphyllin alone is recommended for those with hyperkinetic type of haemodynamics, taking
into consideration its cardiodepressive effects (Ishchenko et al., 1996). The publication did not
give a full description of the controls, which makes it difficult to judge the outcomes of this trial.
Crude drug preparations of Convallaria are not available in Russian pharmacies, but the tincture
(1:10 EtOH 70%) is prescribed in Russia for internal use at a dose of 15-20 drops, 2-3 times per
day as cardiotonic. "Corglycon" is used for intravenous injection at the dose of 0.5-1.0 mL in 1020 mL of glucose (20 or 40% solution), 1-2 times per day (Sokolov, 2000).
5.11. Cardiovascular
5.11.1. FLORES CRATAEGI et FRUCTUS CRATAEGI
In term of Pharmacopoeia USSR, Flores crataegi and Fructus crataegi consists of flowers
Crataegus sanguinea Pall. and flowers and fruits of . laevigata (Poir.) DC., C. chlorosarca
Maxim (syn. . korolkowii hort. ex Dippel), C. wattiana Hemsl. & Lace (syn. . altaica (Loud.)
Lange), . chlorocarpa Lenn, & K. Koch, C. dahurica Koehne ex C.K.Schneid. . monogyna
41
Jacq. (syn. . alemanniensis Cinovskis, . orientobaltica Cinovskis), C. rhipidophylla Gand.
(syn. . curvisepala Lindm.), C. rhipidophylla var. lindmanii (Hrabtová) K.I.Chr. (syn. .
dunensis Cinovskis), . pentagyna Waldst. & Kit. ex Willd., all belong to Rosaceae family.
Dried false fruits and whole or cut, dried flower-bearing branches of of Crataegus monogyna
Jacq. (Lindm.), or C. laevigata (Poir.) D.C. (synonym: C. oxyacantha L.) or their hybrids or a
mixture of these false fruits and whole or cut, dried flower-bearing branches of other European
Crataegus species including C. pentagyna Waldst. et Kit. ex Willd., C. nigra Waldst. et Kit., C.
azarolus L. are included in European Pharmacopoeia.
The pharmacological profile and indications of crataegus are similar in Russia and Europe.
Therefore these questions will be not discussed in the review.
5.12. Haemostatic
5.12.1. HERBA POLYGONI HYDROPIPERIS
Persicaria hydropiper (L.) Delarbre (syn. Polygonum hydropiper L., Polygonaceae), water
pepper is an annual growing to 0.8 m tall plant, and in Russian popular medicine the leaves are
used to stop bleeding and for treating haemorrhoids (Turova and Sapozhnikova, 1989). Water
pepper has been used long time as haemostatic in uterine bleeding, during heavy and painful
menstruation, abortion, and postpartum (Kravkov, 1912, Rossijsky, 1934). The leaves of this
plant have been used to treat cancer, colds, and coughs (Onitsev, 1962). The infusion has been
prescribed for treating rheumatism, chronic ulcers, haemorrhoid, tympanitis, and erysipelas
(Yang et al., 2012). Women of Assam (India) have traditionally used the powdered dry root of P.
hydropiper for the prevention of unwanted pregnancies (Hazarika and Sarma, 2006). Water
pepper is a hot-tasting spice known in China, Japan, and Europe. The sprout of water pepper,
called "mejiso" or "benitade" in Japanese, is a well-known relish for "sashimi," and the seed was
sometimes used as a substitute for pepper in Europe (Matsumoto and Tokuda, 1990). A
42
"Hydropiperinum", chemically characterized extract of P. hydropiper leaves with flavonoid
glycosides, increases blood clotting, reduces the duration of bleeding, and strengthens uterus
contractions (Fedukovich, 1960). Since 1946 aerial parts and liquid extract of P. hydropiper are
included in the State Pharmacopoeia of the USSR (Vereschagin et al. 1959).
The LD50 for the chloroform extract of P. hydropiper leaves was determined to be 760 mg/kg in
male albino mice. Subcutaneous injection of a sub-lethal dose of extract into male mice once a
week for 6 weeks failed to show any significant influence on white and red blood cell count and
blood cholesterol (Rahman et al., 2005). A subchronic toxicity study of water pepper extract
(WPE) was conducted in groups of 10 male and 10 female F344 rats fed powdered diets
containing 62.5, 250, 1000 or 4000 ppm concentrations for 13 weeks. WPE was prepared by
two-step extraction from leaves of P. hydropiper initially with N-hexane and then with ethanol,
containing 7.0% polygodial as a major ingredient. Suppression of body weight gain due to
decreased food consumption was observed in both sexes at 4000 ppm. At this dose, slight
increases of blood urea nitrogen in both sexes and serum alanine aminotransferase, Na and Cl in
females, were observed, suggestive of weak hepatic and renal toxicity, at least in females. The
same females also exhibited slight decrease of red blood cells and haematocrit, slight increase of
mean corpuscular volume and mean corpuscular haemoglobin, and minimal increase of splenic
haemosiderin deposition, providing evidence of slight haemolytic anemia. In addition, enhanced
accumulation of mast cells in the mesenteric lymph nodes induced by WPE treatment might be
related with the complex biological actions on the gastrointestinal environment of polygodial
and/or related ingredients included in this extract. The no-observed-adverse-effect level of WPE
was 1000 ppm translating into 57.4 and 62.9 mg/kg/day for male and female rats, respectively
(Kuroiwa et al., 2006). Table 19 summarizes the pharmacological studies undertaken on
Polygonum hydropiper and reported in the literature.
Table 19 approx. here
43
No clinical data were found on P. hydropiper in the literature available. Aerial part and extract
(70% EtOH) are available in Russia in pharmacies as OTC and recommended for internal
administration at the dose of 1/3 of glass the infusion (1:10), 3-4 times a day or 30-40 drops of
extract, 3-4 times a day as haemostatic (Sokolov, 2000). Polygonum hydropiper is a popular herb
in Russia and its safety and efficacy is confirmed during long time. However, there is lack
information in the public literature about efficacy. Further clinical studies are required to
evaluate the claimed activity in patients and more details on the drug’s safety would be desirable.
5.13. Spasmolytic
5.13.1. FRUCTUS ANETHI GRAVEOLENTIS
Anethum graveolens L (dill, Apiaceae) grows up to 40-60 cm tall. The fruits (seeds) of A.
graveolens have had diverse uses in Russian traditional medicine: in powder form and tincture as
carminative, expectorant and diuretic; decoctions are reported to possess antispasmodic,
sedative, and galactagogue properties; infusion has been recommended as hypothensive
(Gammerman et al., 1984; Lavrenova and Lavrenov, 1997). Dill is also a common household
plant with a very long history of more than 2000 years of use as spice and condiment in food
because of its flavor, as well as preservative. Dill water is believed to have a soothing effect and
is given to babies to treat influenza, relieve hiccups and colics. Chewing the seeds reduces bad
breath. Dill is also a galactagogue that is known to increase the flow of milk in nursing mothers
and is passed to the baby via the milk to help prevent colics. Dill can be used as a regulatory
agent of the menstrual cycle. Dill has been reported to possess antihyperlipidaemic and
antihypercholesterolaemic activity (Heamalatha et al., 2011).
The toxicity of A. graveolens was studied in mice after intraperitoneal injection. The maximum
non-fatal doses of aqueous and ethanolic extracts of A. graveolens fruits were 0.45 g/kg and 5
g/kg (i.p.), respectively. LD50 values of the aqueous and EtOH extracts were 3 g/kg, and 7 g/kg,
44
respectively (Hosseinzadeh et al., 2002). Table 20 summarizes the pharmacological studies
undertaken on A. graveolens and reported in the literature.
Table 20 approx. here
A prospective randomized clinical trial was carried out on 30 hyperlipidemic patients of both
sexes with an age range 44-63 years and a disease duration of 5-10 years. Patients were allocated
into: Group A composed of 15 patients treated with lovastatin tablets 20mg once daily for four
weeks period; Group B composed of 15 patients treated with 500 mg of fine powder of leaves of
A. graveolens, be taken twice daily for four weeks period; in addition 15 healthy subjects serve
as control. Treatment of patients with dill leaves powder results in highly significant P0.01
reduction in the values of total cholesterol (TC) (19.9%), triglyceride (29.5%), LDL-Chol
(22.2%) and VLDL-Chol (25.2%). Statistically significant (P0.05) decrease in TC/HDL-Chol
and LDL-Chol/HDL-Chol after four weeks of treatment, and reduction in TG/HDL-Chol even to
less than that of healthy control was observed. In contrast, treatment with lovastatin significantly
P0.05 decreased all lipid ratios in hyperlipidemic patients after four weeks duration. During the
course of treatment, no side effects were recorded indicating the safety and tolerability of
administered agent (Sahib et al., 2012).
Taking into consideration literature data and the common use of Fructus anethi graveolentis in
Russia and other countries the drug and its preparatiosn should be considered as safe and
effective. Seeds of A. graveolens are available in Russia in pharmacies as OTC and
recommended for internal administration at the dose of 1/3 of glass of the infusion (1:20), 3-4
times per day as spasmolytic (Sokolov, 2000). However publications about clinical trials are far
too limited to allow conclusions about its therapeutic potential. This botanical drug clearly is an
interesting subject for further investigations especially for further clinical tests.
45
5.13.2. RHIZOMATA ET RADICES RUBIAE
In the monograph of Pharmacopoeia USSR Rhizomata et radices Rubiae described as rhizome
and roots of Rubia tinctorum L. (syn. R. iberica (Fish. ex DC). K. Koch). Rubia tinctorum, the
common madder or dyer's madder, is a perennial plant species in the family Rubiaceae with a
height of 60 to 100 cm. Roots of R. iberica have been used in traditional medicine of Kaukaz and
Middle Asia as diuretic (Gammerman et al., 1984). Extract of rubia were reported to decrease the
tension and increase amplitude of renal pelvic and ureter contractions. It promotes motility of
stones and their elimination from kidney and urinary tract (Turova and Sapozhnikova, 1989).
The safety of R. tinctorum was evaluated in mice, rats, and cats. Acute toxicity of an aqueous
extract of madder root was studied during 14-day administration by gavage to (C57Bl/6 ×
C3H)F1 mice. The maximum tolerated dose of extract was between 3500 and 5000 mg/kg body
weight. A subacute toxicity test was performed using 62 mice of each sex, mixing their diets
with R. tinctorum extract at concentrations of 0, 0.3, 0.6, 1.25, 2.5, and 5% for 90 days. All mice
tolerated these doses well. The body weight gains of either sex were not affected by the
treatment. None of the mice treated with extract showed clinical signs of toxicity.
Histopathological examinations showed retention cysts of the kidneys and epidermal vaginal
cysts in a few of the treated or control mice. No hyperplastic, preneoplastic, and neoplastic
lesions and no pathological findings of toxicity were found. It was concluded that dietary
exposure to madder root extract at the doses tested had no significant acute or subacute toxic
effects on mice (Ino et al., 1995). Acute intragastric administration of dry extract of R. tinctorum
root at the doses of 125-15000 mg/g in mice was safe and no side effects were observed. No side
effects were registered after 12 days intragastric administration of dry extract of madder roots
(100 mg/kg) in rats. Extract at the doses of 20-200 mg/kg (intragastric) was safe for cats.
However, an increased dose of up to 400 mg/kg was followed by vomiting, excitation during 3
hours, and subsequent sleeping. The normalization of physiological conditions was after 5 hours
(Vichkanova et al., 2009).
46
Male and female ACI/SegHsd rats, weighing 150–200 g, received a diet supplemented with 1 or
10% R. tinctorum root for 780 days. This root contained lucidin (0.34%), alizarin (0.67%; 1,2dihydroxyanthraquinone) and the primeverosides of both compounds. In the groups receiving
10% madder root diet, 2/16 males and 3/17 females developed hepatocellular adenomas, whereas
none were observed in the controls or the 1% madder root group of either sex. Renal tubule-cell
adenomas were observed in 1/16 males and 2/16 females in the 10% madder root group and a
renal tubule-cell carcinoma in 1/14 males in the 1% madder root group (Westendorf et al., 1998).
Male and female F344 rats were fed diet containing 0%, 2.5%, and 5.0% of 50% ethanol extract
of madder root for 104 weeks. Body weights were significantly decreased in treated groups of
both sexes throughout the feeding period. However, survival rates at week 104 were higher in
treated groups of both sexes than in controls. Relative weights of the kidneys and liver were
significantly increased in treated groups of both sexes. Histopathologically, karyomegaly and
atypical tubules/hyperplasias, as well as renal cell adenomas and carcinomas were significantly
increased in treated groups of both sexes with dose-dependence. Results indicate that extract
exerts carcinogenic potential in the kidney and liver, even with the lower dose studied (Inoue et
al., 2009).
There have been a number of genotoxicity studies of madder color (50% ethanol extract of
madder root) and its constituents. Madder color (MC) was found to be negative in bacterial DNA
repair assays, but positive in reverse mutation assays with or without S9 mix in TA98, TA100
and TA1537 strains (Hachiya et al., 1985). Anthraquinone constituents of MC such as lucidin-3O-primeveroside and its deglycosylated metabolite, lucidin caused DNA adducts in rodents
(Westendorf et al., 1998). Compounds, mollugin, 1-hydroxy-2-methylanthraquinone, 2ethoxymethyl-anthraquinone, rubiadin, 1,3-dihydroxyanthraquinone, 7-hydroxy-2methylanthraquinone, lucidin, 1-methoxymethylanthraquinone and lucidin-3-O-primeveroside,
isolated from the roots of R. tinctorum showed mutagenicity with Salmonella typhimirium TA
100 and/or TA 98 (Kawasaki et al., 1992). Alizarin, a metabolite of 1-hydroxyanthraquinone,
47
was weakly mutagenic in S. typhimurium TA1537 in the presence of S9 and in rat hepatocyte
DNA-repair assays, but it was consistently inactive in transformation experiments with C3H/M2
mouse fibroblasts and in Hprt mutation assays with Chinese hamster V79 cells (Westendorf et
al., 1990).
Taking in account literature data, International Agency for Research of Cancer (IARC, 2002) has
concluded that there is limited evidence in experimental animals for the carcinogenicity of R.
tinctorum and it is not classifiable as to its carcinogenicity to humans (Group 3), however 1hydroxyanthraquinone is possibly carcinogenic to humans (Group 2B). However, the possibility
of a human cancer hazard must be taken into consideration when madder is used chronically for
therapeutic purposes. Table 21 summarizes the pharmacological studies undertaken on
Rhizomata et radices Rubiae and reported in the literature.
Table 21 approx. here
Alizarin, a constituent of the madder root, is employed in phytotherapy to prevent recurrences of
calcium-containing urinary stones. Pharmacokinetic studies were carried out in human subjects.
After giving a single oral dose of 210 mg of alizarin there were two maxima in the serum
concentration curves, the first at 2-4 h and the second at 6-8 h. Alizarin and its glucuronide
conjugate were detected in both maxima by TLC. The mean elimination half-life was 12 h. The
amounts excreted in the urine within 6 days ranged from 18.1 to 36.3%, and the amounts in the
faeces from 21.6 to 33.0% (total recovery: 40-60%). In bile from a patient who had undergone
cholecystectomy only 0.6% of the dose was recovered. To exclude any possibility that alizarin
might be bound to calcium ions in bone, bone trephine specimens were examined from patients
with oxalate stones who had previously been treated with alizarin for several years. No alizarin
was detectable in these samples (Lorenz et al., 1985).
A group of patients (15 male and female, 29-63 years old) with renal pelvis stones (1.5-7 cm)
was treated with 0.5 g of R. tinctorum root extract, to be taken three times a day for 30 days. The
therapeutic results were observed in 11 patients. The publication did not give a full description of
48
the controls, which makes it is difficult to judge the outcomes of this trial. Treatment of patients
results in removal of sand, small stones, and reduction of pyuria. However, the extract was not
effective in 4 patients with big stones. In an other study tablets (0.25 g) of dry extract of R.
tinctorum were used in a clinical trial to treat 22 patients with nephrolithiasis with different
urinary stones localization: kidney (11 patients), urethra (9 patients), bladder (2 patients). Tablets
were administered 3 times per day at the dose of 0.5 g (2 tablets) during 25 days. Positive effects
were observed in 5 patients. The treatment led to removal of sand with urine, and reduction of
pain. But no size decrease of big stones was registered according X-ray examination. No side
effects were registered during both trials (Vichkanova et al., 2009).
Tablets (0.25 g of dry extract standardized with min 8% of ruberitrinic acid) of R. tinctorum
roots are available in Russian pharmacies as OTC and recommended for internal administration
at the dose of 1 tablet, 3 times per day (max 3 tablets, 3 times per day) in 100 mL of warm water
as spasmolytic (Sokolov, 2000). However, the information about chemical composition and
pharmacological effects is insufficient and this is of interest for further study.
5.14. Sedative
5.14.1. HERBA LEONURI
In terms of Pharmacopoeia USSR, Herba Leonuri (motherwort) consists of aerial parts of
Leonurus cardiaca L. and Leonurus quinquelobatus Gilib. (syn. Leonurus cardiaca L. subsp.
villosus (Desf. ex d'Urv.) Hyl.), Lamiaceae collected during the flowering season. The two
species are similar in morphology, the only difference being the degree of hairiness. L.
quinquelobatus has hairs all around the stem, not only on the angles, and the hairs are 1 mm long
and erect. As soon as pharmacological effects of booth plants are similar and L. cardiaca is
included in European Pharmacopoeia it is not reasonable for this review to discuss
pharmacological effects of L. quinquelobatus.
49
5.15. Polyvitamin
5.15.1. FRUCTUS SORBI
Sorbus aucuparia L. (rowan, European rowan, mountain-ash, or European mountain-ash), is a
small to medium-sized deciduous tree typically growing to 8-10 m tall belonging to the
Rosaceae family. The fruit is a small pome of ca. 6-9 mm (rarely up to 14 mm) diameter. The
edible fruits of S. aucuparia have been traditionally used in Russia for diuretic, antiinflammatory, anti-diarrheal, vasoprotective, and vasorelaxant activities, and also as vitamin
source (Turova and Sapozhnikova, 1989; Sokolov, 2000). In Central and Lower Valais
(Switzerland) rowan fruits are used for the treatment of gastrointestinal tract as antiflatulent,
antibloating and against colics (Abbet et al., 2014). As it documented in the VOLKSMED
database fruits of S. aucuparia are used in Austria as tea, syrup, jelly or liqueur for the treatment
of respiratory tract related ailments, like infections, colds, flu, as well as fever, rheumatism and
gout (Vogl et al., 2013). Rowanberry is a good source of vitamin C (up to 490 mg/kg) (Häkkinen
et al., 1999) and it has been used for dietary jellies and jams and as component of syrups and
polyherbal mixtures (Shass, 1952).
Rowanberry is considered of low toxicity. The toxicity is related to the cyanogenic glycoside
amygdalin, and also parascorbic acid, which is irritant to mucous membranes. They are present
in very low concentrations and therefore rarely cause more than gastrointestinal effects
(Campbell, Chapman, 2000). Table 22 summarizes the pharmacological studies undertaken on
S. aucuparia and reported in the literature.
Table 22 approx. here
Capillary protective effect of S. aucuparia in combination with vitamin C and rutin was shown
in patients with myocardial infarct and angina pectoris (Golubenko, 1967). But no details are
available. And no other clinical data was found in the literature.
Dry fruits of S. aucuparia are available in Russia in pharmacies as OTC and recommended for
internal administration at the dose of 1/2 of glass of the infusion (1:20), 2 times a day as
50
polyvitamin (Mashkovskii, 2002). It may be concluded that S. aucuparia fruits can be regarded
as a promising and under-explored fruit which have been used in food in Europe and Asia, and
might find wider applications for medicinal purposes. However pharmacological effects are not
well documented and this subject is interesting for further study.
5.16. Regulation of metabolism, anti-inflammatory
5.16.1. INONOTUS OBLIQUUS
According to the systematic classification, Chaga - also known as birch fungus (Fungus
betulinus) - represents the terrestrial polypore fungus Inonotus obliquus (Pers.) Pil
(Polyporaceae). Chaga has to be collected only from living or freshly cut old birch trees. On dry
standing and fallen trees, chaga is destroyed and the content of active compounds decreases
dramatically (Shashkina et al., 2006).
Traditionally since the 12th century, chaga has been used in Russia for the treatment of
gastrointestinal disorders, cardiovascular diseases, diabetes and even cancer. Allegedly, the
Russian duke Vladimir Monomach was cured from lip cancer by chaga (Artemova, 2001).
Chaga (in various combinations with other medicinal plants) was used for the treatment of
gastric and duodenal ulcers and various forms of gastritis (Artemova, 2001; Kaukin, 2002). The
chaga tea produces an increase of general stamina and has a pain relieving action, is used for
treatment of heart, stomach and liver diseases (Gammerman et al., 1984; Saar, 1991).
Safety of chaga extract was tested on mice, rabbits, dogs, and cats. The extract was well tolerated
in large doses: LD50 for mice was 6.5 g/kg body weight. The extract administered per os in doses
up to 1.0 g/kg did not cause any change in the behavior of rabbits, dogs, and cats (Lazovskaya,
1959). In a chronic administration test, rats and rabbits received a chaga extract in a daily dose of
1.0 and 0.3 g/kg body weight respectively over a period of 5 - 6 months. It was concluded that
chaga is well tolerated in the doses indicated and does not exhibit accumulative toxic effects.
51
The same tests also showed no evidence of pyrogenicity upon per oral administration of chaga in
rabbits (Lazovskaya, 1959) (see Table 23).
Table 23 approx. here
Clinical data indicate that when chaga is administered for extended periods, it has beneficial
effects in the treatment of patients with stage III – IV of cancer, irrespective of the tumor
location. In most of these patients without pronounced cachexia, a 3- to 4-week administration of
chaga led to a decrease and termination of the pain syndrome, which allowed the administration
of narcotic drugs to be stopped (Bulatov et al., 1959; Pyaskovskii, Rikhter, 1961; Shashkina et
al., 2006).
The commercial chaga extract Befungin®, contains EtOH (10%) extract of chaga with 1.76% of
chloride or 2.0% sulfate of cobalt, is manufactured in 8 factories all around Russia. A group of
50 patients (14 women and 36 men) suffering from psoriasis were treated with Befungin® and
chaga extract paste. In 37 of these patients the development of psoriasis was preceded by
diseases of the gastrointestinal tract or liver (hyperacid or hypoacid gastritis, hepatocholecystitis,
gastric ulcer or duodenal ulcer, colitis). In 9 patients these gastrointestinal tract problems
appeared during the existing psoriasis conditions, another 4 patients had accompanying chronic
pharyngonasal cavity conditions. Almost all patients with gastrointestinal disorders were
complaining about pyrosis, belching, unstable stool, intolerance to fatty foods, pain in the right
upper quadrant of epigastric area etc. The patients noted that exacerbation of psoriasis often
coincided with exacerbation of gastrointestinal tract disorders. Duration of the psoriasis
condition before Treatment with Chaga preparations was 1 year in 5 patients, up to 3 years in 7
patients, 7 to 5 years in 8 patients, up to 10 years in 13 patients, from 10 to 15 years in 7
patients, more than 15 years in 10 patients. Among the patients, 3 were suffering from psoriatic
erythroderma, 1 had psoriatic arthritis, 18 had extensive psoriasis with a massive infiltration of
plaques, 20 had extensively spread small plaque rashes, 8 had localized psoriatic plaques. Forty
three patients started the treatment with Chaga during the acute stage of psoriasis, 7 during the
52
steady-state. Chaga extract was heated au-bain-marie and 1 table spoon of extract was diluted in
a glass of boiled water at room temperature. One table spoon of this solution was taken orally, 3
times a day, 20-30 minutes before meals. Water solutions of Befungin® were prepared by
mixings 1 dessert spoon of Befungin® in 100 mL of boiled water (room temperature). The intake
instructions were the same as above. Both Chaga preparations have no unpleasant odor or taste,
and are well tolerated by the patients even after several months of continuous intake. Most of the
patients (42) only used a Chaga preparation for internal use, 8 were also using ointments and one
of the preparations for internal use. Twenty four patients were using Chaga preparations 3-6
months, 18 patients up to 12 months, 8 patients for more than 2 years. The therapeutic effect of
Chaga was manifesting itself only slowly, reaching a maximum at the 3rd month of regular
intake. In most cases disappearance of psoriatic rashes started at the torso, then the scalp, upper
limbs and finally hips and low legs. The Chaga treatment’s normalizing effect on nail plates was
noted after 2-3 months. Extensive psoriasis with massive plaques was completely cured in 14
patients, and improvements were mentioned for 2 patients. Extensive psoriasis with localized
plaques was completely cured in 16 patients, and improvements were mentioned in 3 patients.
Limited psoriasis lesions and erythrodermic lesions were completely cured in 5 and 3 patients,
respectively. Psoriasis-therapy with chaga was especially successful in cases when psoriasis
occurs in combination with chronic inflammatory diseases of gastrointestinal tract, liver and
biliary system. The maximum efficiency of treatment was noted after 9 to 12 weeks of
continuous intake. Additionally, improvement in gastrointestinal functions, increased vitality and
general tonus in all patients was noted after long and regular chaga intake what evidenced about
adaptogenic properties of I. obliquus (Dosychev, Bystrova, 1973).
Chaga and Befungin® are available in Russia in pharmacies as OTC and recommended for
internal administration at the dose of 1/2 of glass the infusion (1:10), 6 times a day or 1 table
spoon of Befungin®, 3 times a day during 3-5 months as regulator of metabolism and in complex
therapy of gastrointestinal diseases (Mashkovskii, 2002). Chaga is well known and popular in
53
Russia and its safety and some evidence for efficacy is based on a long tradition of empirical use.
However, there is lack of information in the public literature about efficacy under controlled
conditions. Further clinical studies are required to evaluate the claimed activity in patients and
more details on the drug’s safety would be desirable. With the recent findings of the importance
of the GI-tract microbiome, studying the effect of chaga on this biome would be of great interest.
5.17. Tonic
5.17.1. RADICES ARALIAE MANDSHURICAE
Aralia elata (Miq.) Seem. syn A. mandshurica Rupr. & Maxim or Japanese angelica tree
(Araliaceae) is an upright deciduous small tree or shrub growing up to 6 m in height, native to
eastern Russia, China, Korea, and Japan. Itse stem and root bark Aralia elata have been used as a
traditional and local medicine in East Asian countries and Russia for the treatment of cough,
diabetes, gastric ulcer, hepatitis, and inflammatory diseases such as rheumatoid arthritis (Namba,
1980; Perry, 1980; Turova and Sapozhnikova, 1989; Ma et al., 2005). The Nanai (“nanaitsy”in
Russian) a Tungusic people of the Russian Far East, have used roots of A. elata for toothache
and stomatitis, as tonic and in liver diseases (Vostrikova, 1973). The Ainu, aboriginal peoples
who once dominated Hokkaido in Japan, have used roots of A. elata (Ayus-ni, enenkeni in
Japan) as a stomachic (Mitsuhashi, 1976). In Russian codified medicine Aralia belongs to the
group of classical adaptogens (Brekhman, Dardymov, 1969).
The toxic acute and subchronic effects of A. mandshurica dried root extract standardized to a
minimum of 3% of aralosides were studied on Sprague-Dawley rats of both sexes after per oral
administration. In the acute toxicity experiment an extract was administered twice a day in
different concentrations. The LD50 was estimated to be 16.5 g/kg and 16.8 g/kg for male and
female rats, respectively. Before death, the animals showed nervous depression, diminution of
the motor activity, frequent micturition, respiratory difficulty and diarrhea. In a subchronic
toxicity the extract was administered per oral at the doses of 0.2, 1.7, 3.4 g/kg over a period of 90
54
days. Depression of the CNS response was not observed. There was an increase in the levels of
aspartate aminotransferase (AST) and serum alkaline phosphatase (SAP) enzymes with a dose of
3.4 g/kg in both sexes on day 90 of administration, but no changes were observed in urea and
serum protein. A significant decrease of the body weight was recorded in both sexes with a dose
of 3.4 g/kg. Moreover, the animals treated with doses of 1.7 and 3.4 g/kg showed a diminution of
fecal consistence. An increase of the liver weight was produced with all the doses of A.
mandshurica, but neither macroscopic nor histological alterations were observed, as in the rest of
the organs. Authors concluded that the extract of Aralia might be accumulated to produce its
toxic effect in the long term (Burgos et al., 1994). The hepatotoxic effect of a dried root extract
of A. mandshurica (standardized to a minimum of 3% of aralosides) was studied over a period of
60 days (0.16 g/kg, 1.5 g/kg and 3 g/kg) in Landrace pigs of both sexes. No changes in
behaviour, external appearance, consumption of food, or body weight was observed. The levels
of alanine amino transferase (ALT) and -glutamil transpeptidase (gGT) were increased
significantly with all the concentrations of A. mandshurica at day 60. SAP did not show
significant differences during the whole experiment. A subclinical hepatitis characterized by the
presence of lymphocytes and polymorphonuclears in the portal and periportal region was
observed (Burgos et al., 1997). The LD50 for mice after per oral administration of the sum of
aralosides (A, B, and C) was 0.47 g/kg (Brekhman, Dardymov, 1969). The acute toxicity of
araloside A (chikusetsusaponin IV) isolated from A. elata was studied in ICR male mice. The
LD50 after 1-week of oral administration was 3.22 g/kg (Lee et al., 2005). Table 24 summarizes
some pharmacological studies undertaken on Aralia and reported in the literature.
Table 24 approx. here
In an open, single arm study including 106 patients treated for various asthenic conditions a
success rate of about 90% using Aralia was reported The administration (3 times per day during
30 days) of 2 mL of A. mandshurica tincture (1:15, EtOH 70%) standardized for aralosides to
patients aged 23 to 60 years with a diagnosis of long-term effects of traumatic brain injury with
55
associated asthenic syndrome and neurotic reactions, depression, neurasthenia, and
psychasthenia significantly increase their working capacity, appetite and sleeping. Decrease of
complaints of fatigue, headaches, and general weakness was observed. Some patients have
reported about increase of sexual potency and libido (Gubina, 1988). Positive effect in patients
with myasthenia syndrome accompanied by chronic post-influenza arachnoiditis was registered
after 2 weeks of treatment with Aralia tincture (Gubina, 1959). The normalization of body
function is one of the main attributes of adaptogens. There were no statistically significant
effects of Aralia tincture on patients with normal blood pressure, although normalization of
blood pressure was observed in patients with hypotension (Turova and Sapozhnikova, 1989).
Aralia has a pronounced positive effect in clinical trials on introverts and people with high levels
of neuroticism. Maximal positive effect was observed during first 4 months of treatment
(Markin, Makrina, 2007; Markina, Makrin, 2008).
The effects of oral treatment with a phytopreparation Aralox containing A. mandshurica and
Engelhardtia chrysolepis Hance (Juglandaceae) extracts on some parameters of lipid
metabolism was studied. Randomized placebo-controlled study was carried out over 15 weeks
and included 32 women with nondiabetic obesity. The patients received Aralox (main group,
n=16) or placebo (control group, n=16) 3 times daily 30-45 min before meals. A single dose of
Aralox included 150 mg A. mandshurica extract containing at least 20% triterpene saponines
(aralosides) and 150 mg extract from Engelhardtia chrysolepis leaves containing at least 20%
flavonoid (dehydroquercetin-3-rhamnoside). Thirteen women from the main group and 14
controls completed the 15-week study. No appreciable differences in physical characteristics and
nutrition of examined patients in the two groups were detected before Aralox/placebo treatment.
Patients receiving Aralox 3 times daily lost 4.3±0.7 kg (p<0.001) over 15 weeks vs. 0.7±0.2 kg
in the placebo group. Body weight loss under the effect of Aralox was nearly exclusively (95%)
due to fat loss. Perilipin content in adipocytes of patients treated with Aralox decreased by 27%.
A course of Aralox treatment promoted an increase in adipocyte HSL activity from 5.2±1.1 to
56
8.1±1.4 U/mg protein while controls had virtually no changes in this parameter. Aralox reduced
the content of plasma triglycerides from 3.6±0.2 to 1.8±0.7 mmol/L; in the controls triglyceride
level did not change (Abidov et al. 2006).
Since 1975 “Saparal" tablets containing a mixture of ammonium salts of aralosides A, B, and C
(0.05 g) have been on the market in the USSR / Russia. Aralosides (A, B and C) stimulate the
central nervous and immune systems, possess anti-stress properties, and protect against
unfavorable environmental conditions such as hypoxia or viral infections. After 36-day training
of swimmers with "Saparal" at the dose of 50 mg/day a range of effects were observed: A
reduction in the level of tissue hypoxia after physical loading due to an increase in the oxidationreduction processes in tissue, promotes strengthening of protective properties of an organism,
raising cytophagous activity of leukocytesSmaller decrease in work capacity during the first twothree days after the high physical loadings was also evident (Sokolov et al., 1971).
It may be concluded that Aralia is a popular plant in traditional medical systems in Russia and
Asia, with a reputation of an adaptogen. The tincture of Aralia and tablets 'Saparal" are available
in Russia in pharmacies by prescription and recommended for internal administration at the dose
of 30-40 drops, 2-3 times a day, or 1 tablet 2-3 times a day for 10-15 days as CNS stimulant and
adaptogen (Sokolov, 2000). However, it is important to reproduce and confirm the non-clinical
studies and perform clinical trials according GCP.
5.17.2. RHIZOMATA ET RADICES RHODIOLAE ROSEAE
Rhizomata et radices Rhodiolae roseae consist of the dried roots and rhizomes of Rhodiola rosea
L. (syn. Sedum roseum (L.) Scop.), (Crassulaceae), commonly golden root, rose root, roseroot,
arctic root), a perennial plant with shoots reaching 5 to 35 cm in height.
Rhodiola rosea is one of the most popular classical plant adaptogens utilized in Russia. In
traditional and popular Russian medicine R. rosea is used to increase physical endurance, work
productivity, longevity, resistance to altitude sickness and to treat fatigue, depression, anaemia,
57
impotence, gastrointestinal ailments, infections and disorders of the nervous system (Turova and
Sapozhnikova, 1989). Already in Linné’s Materia medica (Linné, 1749) the root of Rhodiola is
recommended in the treatment of headaches, "hysteria", hernias, discharges, and as an astringent.
A monograph on its root is also found in the first Swedish national pharmacopoeia (Panossian et
al., 2010). Alm (Alm, 2004) mentioned the use of Rhodiola in popular medicine against scurvy,
being also medically used as a stimulant and in France as an astringent (as described by Virey in
a medical textbook in 1811).
It was first recommended in 1969 by the Pharmacological Committee of the Ministry of Health
of the USSR for use as a stimulant against fatigue by patients who suffered asthenic states and
for healthy people with astheny during periods of high mental exertion or after intensive physical
work. The drug can also be applied in cases of borderline nervous-mental diseases, neuroses,
neurotic disorders and psychopathies. In psychiatric practice, extracts of R. rosea are indicated
for the correction of neurological side-effects associated with psychopharmacological therapy,
and for the intensification and stabilization of remissions in cases of asthenic and apathisticalaboulic type schizophrenia (Saratikov and Krasnov, 1987; 2004: Panossian et al., 2010). Since
1975 Rhodiola liquid extract (1:1, EtOH 40%) has been produced industrially in Russia on a
large-scale. Since 1985 Rhodiola tablets containing R. rosea SHR-5 extract have been on the
market in Sweden. In April 2009 the first R. rosea product registered as a traditional herbal
medicinal product, Vitano (based on the R. rosea extracts WS 1375) was introduced in the UK
(Hung et al., 2011) for use as adaptogen (Box1) in situations of decreased performance such as
fatigue and sensation of weakness (Panossian et al., 2010).
Safety of extract of R. rosea was tested on rats, mice, dogs, and in humans. Rhodiola rosea has a
very low level of toxicity. The LD50 after intraperitoneal injection of liquid extract in mice was
28.6 ml/kg, equivalent to approximately 3360 mg/kg. The equivalent dosage in a 70 kg human
would be about 235 g. Since the usual clinical doses are 200-600 mg/day, there is a huge margin
of safety (Brown et al., 2002). No toxic signs were observed after administration of the glycoside
58
salidroside at the dose of 1000 mg/kg (equivalent of 50 ml/kg of extract). Intragastric
administration of extract (1 ml/kg) or salidroside (20 mg/kg) during 14 days was safe in rabbits.
In a dose range of 10-40 mg/kg salidroside do not affect arterial blood pressure in rabbits after
intraperitoneal and intravenous injections. The LD50 for p-tyrosol, another main compound of R.
rosea, was 2700 mg/kg and 1700 mg/kg in mice after intragastric and intraperitoneal injection
respectively and 7079 mg/kg in rats after intragastric administration. No toxicity was observed
after 3 months chronic intragastric administration of p-tyrosol at the doses of 200 mg/kg in male
rats and 10 mg/kg in dogs (Saratikov, Krasnov, 2004). Salidroside did not show genotoxicity in a
reverse mutation assay (up to a maximal dose of 5,000 μg/plate), a chromosomal aberrations
assay (at doses up to 2000 g/kg, and a mouse micronucleus assay (at doses up to 1500 mg/kg)
(Zhu et al., 2010). No induction of mutations in sexual and somatic cells of rats was observed
after intragastric administration of p-tyrosol at the dose of 2500 mg/kg (Saratikov, Krasnov,
2004). After per oral administration of an ethanol extract from the roots of R. rosea in mice (10316 mg/kg) a significant reduction in exploratory behavior and in the number of rearings and
head dippings were observed, but no changes in the sedative-hypnotic and anticonvulsant
response were registered. Moreover, R. rosea reduced the licking time in the formalin test.
Rhodiola rosea extract (1000 mg/mL) was not toxic for Artemia salina. All these results confirm
the very low risk of intoxications by rhodiola (Montiel-Ruiz et al., 2012).
Rhodiola rosea extract WS® 1375 was safe and generally well tolerated at a dose of 200 mg
twice daily for 4 weeks in the subjects with life-stress symptoms. Two hundred mg of extract (as
dry extract) from R. rosea roots and rhizomes is equivalent to 300–1000 mg of R. rosea roots
and rhizomes (Edwards et al., 2012).
Results of several hundred pharmacological studies of R. rosea are assessed in several review
articles and books (Saratikov and Krasnov, 1987; 2004; Kelly, 2001; Brown et al., 2002;
Panossian and Wagner, 2005; Panossian and Wikman, 2009; Panossian et al., 2010, Hung et al.,
2011; Ishaque et al., 2012). The main pharmacological effects summarized in these reviews are:
59
adaptogenic and stress- protective (neuro-cardio and hepato- protective); stimulating CNS
including cognitive functions such as attention, memory and learning, anti-fatigue,
antidepressive and anxiolytic; life-span increasing; cardioprotective; and endocrine activity
normalizing. It is interesting that the effect of Rhodiola on CNS, does not depend linearly on the
dose. The dose dependent activity curve has a bell shape: in small doses Rhodiola is inactive, in
intermediate dose level active, and in high dose inactive again (Kurkin et al., 2003; Perfumi and
Mattioli, 2007; Wiegant et al. 2009; Panossian et al., 2010). Table 25 summarizes some
pharmacological studies undertaken on Rhodiolae roseae and reported in the literature.
Table 25 approx. here
A systematic review of randomized clinical trials of R. rosea was published by Hung et al.
(2011). Orally administrated for 2-6 weeks dry SHR-5 extract prepared with ethanol-water
(EtOH 70% (v/v) in the daily doses of 288 - 680 mg (1-4 tablets), have been shown to improve
mood (Darbinyan et al., 2007), cognitive performance, attention and relief fatigue (Darbinyan et
al., 2000; Spasov et al., 2000; Shevtsov et al., 2003; Olsson et al., 2009) in stress related
conditions. In endurance exercise performance test 24 healthy volunteers treated with 100 mg of
R. rosea extract (containing 3% rosavin + 1% salidroside) showed significant (p < 0.05) increase
in time to exhaustion, VO2, VCO2, peak O2 output, and peak CO2 output (De Bock et al., 2004).
Facilitation of recovery after exercise was registered after treatment of untrained subjects with
340 mg RHODAX (preparation containing 30 mg active substances of R. rosea extract) twice a
day for 30 days before and 6 days after exhausting physical exercise (Abidov et al., 2004).
Based on abovementioned studies and other data including EMA’s Community herbal
monograph on Rhodiola rosea L. rhizoma et radix (EMA/HMPC/232091/2011), who in 2011
approved its use for the temporary relief of symptoms associated with stress, such as fatigue,
exhaustion and mild anxiety based on traditional use only . R. rosea is a popular plant in
traditional medical systems in the Nordic countries, Eastern Europe and Asia, with a very well
dcoumented reputation as an adaptogen. No major risks have been associated with R. rosea.
60
The extract of Rhodiola is available in Russia in pharmacies as OTC and recommended for
internal administration at the dose of 5-10 drops, 2-3 times a day for 20 days (1-2 months in
psychiatry praxis) as CNS stimulant and adaptogen (Sokolov, 2000). However, it is important to
reproduce and confirm the pre-clinical studies and perform larger scale clinical trials according
GCP.
5.18. No pharmacological group is stated in the Pharmacopoeia
5.18.1. HERBA POLYGONI PERSICARIAE
Persicaria maculosa Gray (syn. Polygonum persicaria L.), Polygonaceae, lady's thumb is a
perennial plant, growing up to 1 m high, and has narrow, lancet-shaped leaves 8-10 cm long. A
decoction and an infusion have been used in Russian traditional medicine for the treatment of
hemorrhoidal bleedings, as laxative and diuretic (Vereschagin et al., 1959). The infusion of P.
persicaria is recommended in the therapy of patients with atonic constipation (Sokolov, 2000).
The infusion and EtOH (70%) extract of the aerial parts increase gastrointestinal motility, induce
vasoconstriction in blood vessels, increase blood viscosity and activate blood coagulation in
rabbits (Samarina, 1950). Antihypertensive properties were shown in frogs and guinea pigs
(Samarina, 1948). A laxative effect and increased diuresis were observed in mice after
administration of an EtOH (70%) extract of P. persicaria (Belikova, 1944).
Reportedly, the aerial parts of P. persicaria have very low toxicity (Sokolov, 2000), but no
details are available. A limited number of pharmacological studies about Herba polygoni
persicariae are available (Table 26).
Table 26 approx. here
Single arm, uncontrolled, non-blinded study was performed on group of 34 patients suffering
from hemorrhoids. Patients were treated with an infusion of P. persicaria three times a day
before meals for 7-21 days at doses of 1 tablespoon upto100 mL. Positive results were observed
61
in 27 patients. Subjective complaints decreased, bowel movements became regular, bleeding
stopped completely or were reduced, and a diuretic effect was observed (Turova and
Sapozhnikova, 1989).
Aerial parts of P. persicaria are available in pharmacies as OTC, and is recommended at the dose
of 1 table spoon of infusion (1:100) 3 times per day to treat chronic atonic constipation and
hemorrhoids (Sokolov, 2000). However, the chemical and pharmacological evidence to support
the medical applications especially as antihypertensive is from the early 1940th of and needs
further confirmation.
5.18.2. HERBA THERMOPSIDIS LANCEOLATAE
Thermopsis lanceolata R. r. (bush pea, Leguminosae) is a perennial plant attaining 40 cm in
height. The aerial part is harvested before flowering. Decoctions are used in Russia to treat
respiratory catarrh, flu, bronchitis, pneumonia and headaches (Akopov, 1990; Mamedov,
Cracker 2001). In China T. lanceolata is used for breath stimulation, and prevention of cough (Li
et al., 2007). The dry extract of Thermopsis (25% EtOH as extragent) was proposed in USSR in
1933 as expectorant, as well as promoting thinning and removal of secretions (Vereschagin et al.,
1959). The standardized extract Cytiton (0.15% cytosine obtained from the seeds of T.
lanceolata) was prescribed to stimulate respiratory function and improve blood circulation, to
treat asphyxia (Khalmatov et al., 1984; Gammerman et al., 1984).
Various extracts of T. lanceolata were all shown to be toxic. The toxicity of MeOH extract was
studied in mice after per oral administration. All mice died in 2-2.5 min after single acute
administration of 300 mg/kg extract. After 60 days chronic administration at a dose of 50 mg/kg
it was toxic (Zhu et al., 2003). Intoxication resulted in paroxysmal supraventricular and
ventricular tachycardia and extrasystoles (Chatval, 2009). In low doses dry extracts of T.
lanceolata excite the respiratory center, in high doses they can cause vomiting and paralyze the
centers of brain and medulla oblongata. Maximal single dose of aerial part for adults is 0.1 g, and
62
daily dose is 0.3 g (Sokolov, 2000). Acute toxicity of cytisine (main quinolizidine alkaloid) was
studied in rats and mice. The estimated LD50 was 5-50 mg/kg body weight in rat after per-oral
administration. In repeated dose toxicity studies, cytisine was given to the rats for 30 and 90 days
in dose 7.6 mg/kg and dose up to 1.35 mg/kg, respectively. No changes in clinically laboratory
parameters and histomorphological changes in experimental animals were observed. When
applied chronically in mice (3.3 mg/kg) for 45 days and in rats (0.45 and 0.9 mg/kg) and dogs
(0.45 mg/kg) for 6 months, cytisine does not cause any changes in clinical laboratory and
histomorphological parameters in animals, but some light liver dystrophic changes were
observed (Tzankova and Danchev, 2007). Overall, only very limited pharmacodynamics data
are available.
No clinical data on T. lanceolata were found. At the moment the aerial part of T. lanceolata is
not available in pharmacies. "Cough tablets" (0.0067 g of powder of aerial part of T. lanceolata
and 0.25 g of NaHCO3) are available in Russia in pharmacies as OTC and recommended as
expectorant at the dose of 3 tablets per day during 3-5 days. Tablets with 0.05 g of standardized
dry extract of T. lanceolata (1% of alkaloids) are recommended for adults as expectorant at a
dose of 2-3 tablets per day (Sokolov, 2000). The dry cough mixture with 0.045 g of standardized
dry extract of T. lanceolata per dose is recommended for adults as expectorant at a dose of 1
dose dissolved in table spoon of water 3-4 times per day (Mashkovskii, 2002). The information
about chemical and pharmacological effects is insufficient and the drug’s use cannot be
recommended until more detailed studies especially on its safety become available.
6. Conclusions
This article provides a review of the data on medicinal plants included in the Russian
Pharmacopoeia which for many years have been used in the officinal Russian medicine and
which not very well known as a medicine outside of its region of origin. Only 83 medicinal
plants are refered in the State Pharmacopoeia of USSR 11th ed. in results of sophisticated
63
scientific investigation and practical evaluation. All medicinal plants were evaluated by drug
regulatory affairs professionals according to state standards. The in vivo and in vivo effects as
well as in some cases the effectiveness and safety of HMP have been studied in considerable
detail, However, our analysis is limited, for example, by the fact that a lot of unpublished
documents are deposited in the regulatory archive and not available to the public.
During most of the Soviet period the country was closed not only from political point of view but
all scientific information was very limited. A lot of scientific articles were newer trnaslated in
English and a lot of information collected by scientists was not available for the international
community. In this review we summarised data, published in Russia and in other countries
related to medicinal plants which have log history of often well studied applications in the
Russian Federation and the review highlights the potential for further developing these herbal
medicines
Most importantly, the Soviet / Russian scientists contributed significantly to the development of
plant-derived adaptogens – tonics, playing important role in regulation of metabolism. Aralia,
rhodiola, chaga are good examples and have been studied extensively (especially in the USSR /
Russia). Modern research on molecular mechanisms of action are essential for better
understanding the effects of adaptogens, and its potential to improve many aspects of
neuropsychiatric disorders, including perceived energy levels, cognitive function, memory,
attention, and mental and physical performance, particularly under stress.
A great potential is embodied in group of plant with expectorant effect. However, further studies
are required for using the promising potential of these plants for a more efficient treatment. In
this as in other cases the risks of adulterations must be monitored carefully.
Four unique plants of Pharmacopoeia of USSR are belonging to group of diuretics and three to
astringent. It is interesting that rhizomes of Bergenia crassifolia are known as astringent, but
leaves are appearing to meet the criteria of being an adaptogen. A number of positive effects,
64
especial antihypertensive, are attributed to G. uliginosum. However publications about chemistry
and pharmacological effects are fragmentary.
We hope that this analysis will foster more detailed research on some of these medicinal plants.
It is important to reproduce and confirm the non-clinical studies and perform clinical trials of
mentioned medicinal plants according Good Clinical Practice.
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103
Table 1. Monographs for medicinal plants included in the State Pharmacopoeia of the USSR,
11th edition
Monograph title
1. CORMUS LEDI
PALUSTRI
2. CORTEX FRANGULAE
ALNI
3. CORTEX QUERCUS
4. CORTEX VIBURNI
5. FLORES CALENDULAE
6. FLORES CENTAUREAE
CYANI
7. FLORES
CHAMOMILLAE
8. FLORES CRATAEGI
9. FLORES HELICHRYSI
ARENARII
10. FLORES SAMBUCI
NIGRAE
11. FLORES TANACETI
12. FLORES TILIAE
13. FOLIA BELLADONNAE
14. FOLIA DIGITALIS
15. FOLIA EUCALYPTI
VIMINALIS
16. FOLIA FARFARAE
Latin name of plant, family (as in
the State Pharmacopoeia of the
USSR)
Ledum palustre L., Ericaceae
Expectorant
Frangula alnus Mill., Rhamnaceae
Laxative
Quercus robur L.
Querqus petrae Liebl., Fagaceae
Viburnum opulus L, Caprifoliaceae
Calendula officinalis L., Asteraceae
Astringent
Centaurea cyanus L., Asteraceae
Chamomilla recutita (L.) Rauschert
(Matricaria recutita L., M.
chamomilla L.), Asteraceae
Crataegus sanguinea Pall.;
. laevigata (Poir.) DC.
[syn. . oxyacantha sensu Pojark.]
. korolkowii L. Henry
. altaica (Loud.) Lange
. chlorocarpa Lenne et . Koch
. dahurica Koehne ex Schneid.
. monogyna Jacq.
. alemanniensis Cin.
. orientobaltica Cin.
. curvisepala Lindm.
. curonica Cin.
. dunensis Cin.
. pentagyna Waldst. et Kit.,
Rosaceae
Helichrysum arenarium (L.)
Moench, Asteraceae
Sambucus nigra L., Caprifoliaceae
Tanacetum vulgare L., Astera
Tilia cordata Mill.
T. platyphyllos Scop., Tiliaceae
Atropa bella-donna L., Solanaceae
Digitalis purpures L.
D. grandiflora Mill. (syn. D.
ambigua Murr.), Scrophulareaceae
Eucalyptus viminalis Labill.,
Myrtaceae
Tussilago farfara L., Asteraceae
Pharmacological group
Diuretic
Antiseptic and antiinflammatory
Diuretic
Anti-inflammatory,
spasmolytic
Cardiovascular
Choleretic
Diaphoretic (sudorific)
Antihelminthic and
choleretic
Diaphoretic (sudorific)
Cholinolytic
(spasmolytic)
Cardiotonic
Anti-inflammatory
Expectorant
104
17. FOLIA HYOSCYAMI
Hyoscyamus niger L., Solanaceae
18. FOLIA MENTHAE
PIPERITAE
19. FOLIA MENYANTHIDIS
TRIFOLIATAE
20. FOLIA PLANTAGINIS
MAJORIS
21. FOLIA
ORTHOSIPHONIS
STAMINEI
22. FOLIA SALVIAE
23. FOLIA SENNAE
24. FOLIA STRAMONII
Mentha piperita L., Lamiaceae
25. FOLIA URTICAE
26. FOLIA UVAE URSI
Urtica dioica L., Urticaceae
Arctostaphylos uva-ursi (L.)
Spreng., Ericaceae
Vaccinium vitis-idaea L., Ericaceae. Diuretic
Alnus incana (L.) Moench
Astringent
A. glutinosa (L.) Gaertn.,
Betulaceae
Anethum graveolens L., Apiaceae
Not claimed,
Spasmolytic*
Pimpinella anisum L.
Not claimed,
(Anisum vulgare Gaertn.), Apicae
Expectorant*
Carum carvi L. Apiaceae
Not claimed,
Spasmolytic*
Crataegus laevigata (Poir.) DC.
Cardiovascular
(C. oxyacantha sensu Pojark.)
. korolkovii L., Henry
. altaica (Lond.) Lange
C. chlorocarpa Lenne
. dahurica Koehne ex Schneid.
. monogina Jacq.
. alemanniensis Cin.
. pentagyna Waldst. et Kit.
. orientobaltica Cin.
. curvisepala Lindm.
. curonica Cin.
. dunensis Cin.,
Rosaceae
Foeniculum vulgare Mill., Apiaceae Not claimed,
Spasmolytic*
Juniperus communis L.,
Diuretic
Cupressaceae
Vaccinium myrtillus L., Ericaceae
Astringent
Padus avium Mill.
Astringent
P. asiatica Kom., Rosaceae
Rhamnus cathertica L.,
Laxative
Rhamnaceae
Rosa majalis Herrm.
Polyvitamin
27. FOLIA VITIS-IDAEA
28. FRUCTUS ALNI
29. FRUCTUS ANETHI
GRAVEOLENTIS
30. FRUCTUS ANISI
VULGARIS
31. FRUCTUS CARVI
32. FRUCTUS CRATAEGI
33. FRUCTUS FOENICULI
34. FRUCTUS JUNIPERI
35. FRUCTUS MYRTILLI
36. FRUCTUS PADI
37. FRUCTUS RHAMNI
CATHARTICAE
38. FRUCTUS ROSAE
Menyanthes trifoliata L.,
Menyanthaceae
Plantago major L., Plantaginacea
Cholinolytic
(spasmolytic)
Spasmolytic and
choleretic
Bitterness (appetite
stimulant) and choleretic
Expectorant
Orthosiphon stamineus Benth.,
Lamiaceae
Diuretic
Salvia officinalis L., Lamiaceae
Cassia acutifolia Del., Fabaceae
Datura stramonium L., Solanaceae.
Anti-inflammatory
Laxative
Cholinolytic
(spasmolytic)
Haemostatic
Diuretic
105
39. FRUCTUS SORBI
40. FRUCTUS VIBURNI
41. GEMMAE BETULAE
42. GEMMAE PINI
43. HERBA ADONIDIS
VERNALIS
44. HERBA ARTEMISIAE
ABSINTHII
FOLIA ARTEMISIAE
ABSINTHII
45. HERBA BIDENTIS
46. HERBA BURSAE
PASTORIS
47. HERBA CHELIDONII
48. HERBA CENTAURII
49. HERBA
CONVALLARIAE
FOLIA CONVALLARIAE
FLORES CONVALLARIAE
50. HERBA EQUISETI
ARVENSIS
51. HERBA GNAPHALII
ULIGINOSI
52. HERBA HYPERICI
(R. cinnamomea L.),
R. acicularis Lindl.,
R. davurica Pall.,
R. beggeriana Schrenk,
R. fedtschenkoana Regel,
R. canina L.,
R. corymbifera Borkh.,
R. micrantha Smith,
R. kokanica (Regel) Regel ex Juz.,
R. psammophila Chrshan.,
R. tomentosa Smith,
R. zangezura P. Jarosch.,
R. rugosa Thunb.,
Rosaceae
Sorbus aucuparia L., Rosaceae
Viburnum opulus L., Caprifoliaceae
Betula pendula Roth
B. pubescens Ehrh., Betulaceae.
Pinus silvestris L., Pinaceae
Adonis vernalis L., Ranunculaceae
Polyvitamin
Diaphoretic, antiinflammatory
Diuretic
Expectorant
Cardiotonic
Artemisia absinthium L.,
Asteraceae.
Bitterness (appetite
stimulant) and choleretic
Bidens tripartita L., Asteraceae.
Anti-inflammatory for
external use
Not claimed,
Haemostatic*
Anti-inflammatory for
external use
Bitterness (appetite
stimulant)
Capsella bursa - pastoris (L.)
Medik., Brassicaceae
Chelidonium majus L.,
Papaveraceae
Centaurium erythraea Rafn [syn.:
C. minus Moench, C. umbellatum
Gilib., Erythraea Centaurium (L.)
Borkh]
C. pulchellum (Sw.) Druce [syn.:
Erythraea pulchella (Sw.) Hornem],
Centianaceae
nvallaria majalis L.,
C. transcaucasica Utkin ex Grossh.
C. keiskei Mig.
Liliaceae
Equisetum arvense L., Equisetaceae
Gnaphalium uliginosum L.,
Asteraceae
Hypericum perforatum L.
H. maculatum Crantz
(H. quadrangulum L.),
Cardiotonic
Diuretic
Not claimed,
Hypotensive, antiinflammatory,
choleretic*
Astringent, antiseptic
106
53. HERBA MILLEFOLII
54. HERBA LEONURI
55. HERBA ORIGANI
56. HERBA POLYGONI
AVICULARIS
57. HERBA POLYGONI
HYDROPIPERIS
58. HERBA POLYGONI
PERSICARIAE
59. HERBA
THERMOPSIDIS
LANCEOLATAE
60. HERBA SERPYLLI
61. HERBA THYMI
VULGARIS
62. HERBA VIOLAE
63. INONOTUS OBLIQUUS
64. RADICES ALTHAEAE
65. RADICES ARALIAE
MANDSHURICAE
66. RADICES GINSENG
67. RADICUS ONONIDIS
68. RADICES RHEI
69. RADICES TARAXACI
70. RHIZOMATA
BERGENIAE
71. RHIZOMATA
BISTORTAE
72. RHIZOMATA CALAMI
73. RHIZOMATA ET
RADICES INULAE
74. RHIZOMATA CUM
Hypericaceae
Achillea millefolum L., Asteracea
Leonurus cardiaca L.
(L. cardiaca L. subsp. villosus
(Desf.) Jav.
Leonurus quinquelobatus Gilib.,
Lamiaceae.
Origanum vulgare L., Lamiaceae
Polygonum aviculare L.,
Polygonaceae
Polygonum hydropiper L.,
Polygonaceae
lygonum persicaria L.,
Polygonaceae.
Thermopsis lanceolata R. r.,
Fabaceae
Thymus serpyllum L., Lamiaceae.
Thymus vulgaris L., Lamiaceae
Viola tricolor L.
V. arvensis Murr., Violaceae
Inonotus obliquus (Pers.) Pil.,
Hymenochaetaceae
Althaea officinalis L.
A. armeniaca Ten., Malvaceae.
Aralia elata (Miq.) Seem.
(A. mandshurica Rupr. et maxim.),
Araliaceae.
Panax ginseng `. {. !|.,
Araliaceae
Ononis arvensis L., Fabaceae
Rheum palmatum L. var tanguticum
Maxim., Polygonaceae
Taraxacum officinale Wigg.,
Asteraceae
Bergenia crassifolia (L.) Fritsch,
Saxifragaceae.
Polygonum bistorta L.
P. carneum `. Koch, Polygon.
Acorus calamus L., r
Not claimed,
Haemostatic, antiinflammatory
Sedative
Expectorant
Not claimed,
Diuretic*
Haemostatic
Not claimed,
medicine of natural
origin
Not claimed,
medicine of natural
origin
Expectorant
Expectorant
Expectorant
Not claimed,
Regulation of
metabolism, antiinflammatory*
Expectorant
Not claimed,
Tonic*
Tonic
Not claimed,
medicine of natural
origin
Laxative
Bitterness (appetite
stimulant) and choleretic
Astringent, for external
use
Astringent
Inula helenium L., Asteraceae
Bitterness (appetite
stimulant) and choleretic
Expectorant
Polemonium caeruleum L.,
Expectorant
107
RADICIBUS POLEMONII
75. RHIZOMATA ET
RADICES RHODIOLAE
ROSEAE
76. RHIZOMATA }>
RADICES RUBIAE
77. RHIZOMATA CUM
RADICIBUS VALERIANAE
78. SEMINA CUCURBITAE
Polemoniaceae.
Rhodiola rosea L., Crassulaceae
Rubia tinctorum L.
R. iberica (Fish. ex DC). `. Koch,
Rubiaceae
Valeriana officinalis L.,
Valerianaceae
Cucurbita pepo L.,
C. maxima Duch.
C. moschata (Duch.) Poir.,
Cucurbitaceae
Linum usitatissimum L., Linaceae
Schisandra chinensis (Turcz.) Baill.,
Schisandraceae
Picea abies (L.) Karst., Pinaceae
Tonic
Not claimed,
Spasmolytic*
Sedative
Antihelminthic
79. SEMINA LINI
Ambient
80. SEMINA
Tonic
SCHISANDRAE
81. STROBILI PICEAE
Anti-inflammatory
ABIETIS
82. STYLI CUM
Zea mays L.,
Choleretic
STIGMATIS ZEAE MAYDIS
83. THALLI LAMINARIAE
Laminaria saccharina (L). Lam.,
Laxative
Laminariaceae
*Pharmacological group according to the on line State Register of Medicinal preparations.
108
Table 2. Summary of Pharmacological Studies for B. tripartita
Activity
Model
Plan Extract
Admin
Dosage/
tested
used
t
type
duratio
part
n
used
Methylen 96 well 10 g
Anticance In vitro. Not
per well
speci e chloride plate
r
Mouse
extract,
leukemi fied
soxhlet
a cells
L1210,
AntiIn vivo.
inflammat Carrage
ory
enaninduced
edema
in rats
Antimicro In vitro.
bial
Broth
microdil
ution
method
In vitro.
Disc
diffusio
n test
Per oral
Crude
aqueous
infusion
(1:20
w/v).
Active
compoun
ds: (±)catechin,
chlorogen
ic acid,
caffeic
acid,
luteolin7-Oglucoside,
chicoric
acid,
rosmarini
c acid,
luteolin,
hydroxyci
nnamic
acid,
glycoside
of
luteolin,
polyacetyl
enes
Aqueous, In vitro.
Dry
flow MeOH/w
ater,
er
head acetone/w
s and ater and
herbs MeOH.
MeOH
extract
partitione
d between
diethyl
ether,
Aeri
al
part
Control
Results
Refere
nce
Positive
control
Methotre
xate
Negative
control
Negative
4, 10,
,
20
Indomet
mL/kg
12 h and hacin, 5
mg/kg
at 2 h
before,
and
immedi
ately
after,
injectio
n of
carragee
nan
100%
growth
inhibitio
n
Goun et
al.,
2002
51.1%
inhibitio
n of
edema
at the
dose of
20
mL/kg,
compara
ble to
indomet
acin.
Antipyr
etic
effect
(normali
zation of
paw
temperat
ure) in 1
h
Pozharit
skaya et
al.,
2010
No data
Weak
activity
against
Grampositive
bacteria
(MIC>1.
5
mg/mL)
no effect
on
Gram-
Tomczy
kowa et
al.,
2008
Grampositive:
Bacillus
subtilis,
Microco
ccus
luteus,
Staphylo
coccus
aureus.
Gramnegative:
109
EtOAc
and nBuOH.
Dominati
ng
flavonoid
in herb:
cynarosid
e; in
flower
heads flavanoma
rein
Essential
oils by
hydrodist
yllation
Antioxida
nt
Escheric
hia coli,
E. coli
(lactamas
e+),
Klebsiell
a
pneumon
iae
(ESBL+)
,
Pseudom
onas
aerugino
sa,
Fungi:
Candida
albicans,
C.
parapsil
osis,
Aspergill
us
fumigatu
s, A.
terreus
In vitro.
DPPH
assay
Dry
flow
ers
and
herb
Aqueous,
MeOH/w
ater,
acetone/
water and
MeOH
crude
extracts
In vitro.
DPPH
assay
Aeri
al
part
Isoookani In vitro.
n 7-Oglucoside,
luteolin 7O
glucoside,
luteolin
In vitro.
negative
.
Oil from
flower
heads
activity
fourtime
higher
than
from the
herb.
Fungista
tic effect
of oils,
highest
gainst
C.
albicans
and C.
parapsil
osis
Radical
scavengi
ng for
MeOH/
water
extract
of
flowers
- 68% ;
for
acetone/
water
extract
of herb 66%
Radical
scavengi
ng :
25% for
luteolin
7-O
glucosid
e, 41%
for
luteolin
Wolnia
k et al.
2007
Wolnia
k et al.
2007
110
Negative
control
100%
thrombi
n
inhibitio
n
Goun et
al.,
2002
Intragast 500
ric
mg/kg
No data
Muto et
al.,
1994
Crude
EtOH
extract
(20-96%),
crude
chlorofor
m extract
Per oral
200
mg/kg,
6 days
Negative
, Carsil,
100
mg/kg
Crude
EtOH
extract
(40,
96%),
crude
chlorofor
m extract
Intraperi
toneal
Negative
100
control
mg/kg,
single
administ
ration
Antiulce
r
activity
against
aspirininduced,
but not
against
indomet
hacininduced
ulcers.
EtOH
extract
(40%)
was
most
effective
.
Decreas
e of
ALT
(51%),
ALP
(40%),
TG
(53%),
increase
of
glycoge
n
(117%)
in liver
Decreas
e of
systolic
blood
pressure
in 35%
after 50
min
(40%
EtOH
extract).
Decreas
In vitro.
Thrombi
n
solution
from
bovine
plasma
In vivo.
Aspirininduced
ulcer.
Indomet
hacininduced
ulcer of
rats
Not
speci
fied
Methylen
e chloride
extracts,
soxhlet
96 well
plate
Aeri
al
part
Crude
MeOH
and
aqueous
extracts
In vivo.
CCl4
induced
hepatitis
of rats
Aeri
al
part
Hypotensi In vivo.
ve
Outbree
d rats
Aeri
al
part
Antithro
mbin
Antiulcer
Hepatopr
otective
50L
Mikaeli
an et
al.,
2006
Stepano
va et
al.,
2006
111
e of
blood
pressure
20%
during
5-60
min of
experim
ent
(chlorof
orm
extract)
112
Table 3. Summary of Pharmacological Studies for V. opulus fruits
Activity
Model Pla Extract
Admin
Dosage/ Control
tested
used
nt type
duratio
pa
n
rt
use
d
Drinking Negative
Fru Juice (65% Per oral
Anticanc In
control
of juice
it
pulp, 45%
er
vivo.
instead
water)
Mice,
of water.
1,230
dimeth
weeks
ylafter
hydraz
first
ine
DMH
(DMH
injection
)), 18
induce
after last
d
DMH
colon
injection
cancer
Antimicr
obial
In
vitro.
Agar
well
diffusi
on
metho
Fru Fresh
In vitro.
it
juice,
standardize
d by
phenolics
and
anthocyani
Wells
with 50
l of
juice
Grampositive:
S.
aureus,
S.
epidermi
dis, B.
Results
Refere
nce
Higher
number
of lowgrade
dysplasia
and
lower
number
of other
type
lesions
(highgrade
dysplasia
,
intramuc
osal
carcinom
a and
invasive
carcinom
a) in
treated
groups
indicate
that juice
prevents
progress
of
establish
ed
tumors
but not
chemical
inductio
n of
colonic
tumors.
Strong
inhibitio
n of
S.typhim
urium
(inhibitio
n zone
Ulger et
al.,
2012.
esonie
n et
al.,
2012
113
d
Antimicr
In
ns.
Fru MeOH
In vitro.
No data
subtilis,
Listeria
monocyt
ogenes,
Enteroco
ccus
faecalis,
Micrococ
cus
luteus.
Gramnegative:
Pseudom
onas
aerugino
sa,
E. coli,
Salmonel
la
typhimur
ium, S.
agona
Yeast:
Debaryo
myces
hansenii,
Trichosp
oron
cutaneu
m,
Kluyvero
myces
marxianu
s var.
lactis,
Torulasp
ora
delbruec
kii,
Saccharo
myces
cerevisia
e,
Saccharo
myces
cerevisia
e
12R,
Candida
parapsilo
sis
Negative
25.330.3
mm), S.
agona
(23.327.7
mm), L.
monocyt
ogenes
(26.5±0.
35 mm),
E.
faecalis
(25.7
mm),
and S.
aureus
(24.1
mm).
Most
resistant:
P.
aerugino
sa, M.
luteus, S.
epidermi
dis.
No or
little
antifung
al
activity
was
observed
Most
Sagdic
114
obial
vitro.
Agar
well
diffusi
on
metho
d
Antioxida In
nt
vitro.
DPPH
assay
In
vitro.
DPPH
assay
In
vitro.
ABTS
assay,
DPPH
assay,
NO
scaven
ging,
supero
xide
anion
scaven
ging,
inhibiti
on of
lipid
its
extract (10
and 15%)
Fru Flesh,
In vitro.
it
standardize
d by
malic,
oxalic,
citric acids,
total
phenolic,
total
flavonoid,
and total
anthocyani
n contents
Fru Seeds,
In vitro.
it
standardize
d by
malic,
oxalic,
citric acids,
total
phenolic,
total
flavonoid,
and total
anthocyani
n contents
Fru Fruit
In vitro.
it
extract
(25%)
standardize
d by total
phenolic
and
ascorbic
acid
contents
control.
sensitive
:
Aeromon
as
hydrophi
la, most
resistant
Yersinia
enteroco
litica
EC50 =
24.56
mg/mg
et al.,
2006
No data
Negative
control.
No data
Negative
control.
EC50 =
2.35
mg/mg
Cam et
al. 2007
No data
Negative
control.
Inhibitio
n of NO
(21.8925.44%),
superoxi
de anion
(25.1328.50%),
and lipid
peroxidat
ion
(11.20–
13.90%).
In DPPH
test 8.69.8
ascorbic
Rop et
al.,
2010
Cam et
al. 2007
115
peroxid
ation
Gastropro In
tective
vivo.
Rats,
water
immer
sion
restrai
nt
stress
Dr
y
fru
its
Proanthocy Intragastri 25, 50,
anidins, no c
75
compositio
mg/kg
n
Fru WaterImmuno- In
it
soluble
stimulatin vitro.
Periton
polysaccha
g
eal
ride
cells of
fractions
rats.
from the
squeezed
96 well
plate
Activity
of
myeloper
oxidase
in the
Polisach
arides,
10
g/mL
Negative
control
Negative
control
acid
equivale
nt/kg of
fresh
fruits
(AAE/kg
FM) and
9.1-11.1
AAE/kg
FM in
ABTS
test
Potent
gastrodu
odenoprotectiv
e activity
via an
increase
in
endogen
ous NO
generatio
n,
suppressi
on of
lipid
peroxida
tion and
mobiliza
tion of
antioxida
nt
activity
and
changes
in
glycocon
jugate
content
of the
gastrodu
odenal
mucosa
of rats
Increase
the
phagocyt
ic index
in 31%
and the
secretion
Zayach
kivska
et al.,
2006
Ovodov
a et al.,
2000
116
fruits.
Acidic
polysaccha
rides with
-l,41inked
residues of
Dgalacturoni
c acid,
galactose,
arabinose,
and
rhamnose.
Neutral
polysaccha
rides
composed
of
galactose
and
mannose.
macropha
ges
Petri
dishes,
phagocyti
c
index of
the
macropha
ges by
light
microsco
py
of
lysosom
al
enzymes
with
peritonea
l
macroph
ages in
68%
117
Table 4. Summary of Pharmacological Studies for G. uliginosum
Activity
Model
Plan Extract
Admi Dosage/
tested
used
t
type
n
duration
part
used
10 g
96
Anticance In vitro. Aeri Methylene
per well
well
chloride
al
r
Mouse
and MeOH plate
leukemia part
extracts,
cells
soxhlet
L1210,
Antidiabe
tic
In vivo.
Rats,
epinephr
ine
induced
hypergly
cemia.
Rats,
alloxan
induced
diabetes
Aeri
al
part
Crude
aqueous
decoction
(1 g in 10
mL)
Intrag
astric
Antithro
In vitro.
Not
Methylene
96
Contro
l
Results
45%
growth
inhibition
by
methylen
e chloride
extract,
38%
growth
inhibition
by
MeOH
extract
Negativ The level
25
of
mL/kg, 6 e
control glucose
days
was
decreased
25%, and
glycogen
in liver
was
increased
1.7 fold
compared
to control
the
glucose
tolerance
test
(epinephr
ine
induced
hypergly
cemia).
Decrease
of
glucose
19% but
no effect
on blood
insulin
level
(alloxan
induced
diabetes).
50L
Negativ 75%
Positive
control
Methotr
exate
Negativ
e
control
Refere
nce
Goun
et al.,
2002
Molok
ovskii
et al.,
2002
Goun
118
well
plate
Thrombi
n
solution
from
bovine
plasma
Gastropro In vivo.
tective
Experim
ental
gastric
dystroph
y
by
stomach
alteratio
n in
reserpini
zed or
immobili
zed mice
speci
fied
chloride
and MeOH
extracts,
soxhlet
Not
speci
fied
Per
Isolated
gnaphalosid oral
e A ([7-(6''Ocaffeoyl]O--Dglucopyran
osido-5,4'dihydroxy6,3'dimethoxyf
lavone)
Hypotens
Aeri
Crude
mbin
In vivo.
Per
e
control
thrombin
inhibition
by
methylen
e chloride
extract
Negativ Decrease
50
total
e
mg/kg
Immedia control number
of
tely
stomach
before
lesions
and 5 h
(by 1.6
after
fold),
immobili
including
zation or
small
reserpine
pulverize
injection
d (l.7
fold) and
large
bandlike
(2.3 fold)
lesions
compared
with
control
(reserpini
zed
mice).
Decrease
of
number
of lesions
of any
type (by
2.6 to 3.l
fold) and
number
of
animals
with
various
gastric
lesions
(2.5 fold)
compared
with
control
(immobil
ized
mice.).
50
Negativ Decrease
et al.,
2002
Barnau
lov et
al.,
1984
Makaro
119
ive
SHR rats
al
part
oral
aqueous
extract.
gnaphalosid
e A;
6"-caffeyl7--Dglucopyran
osyloxy4',5dihydroxy3',6'
dimethoxyf
lavone;
3',4',5,7tetrahydrox
y-6methoxyfla
vone 7-0(6"O-caffeyl-Dglucopyran
oside);
6methoxylut
eolin,
6hydroxylute
olin 7-O-
-Dglucopyran
oside
mg/kg,
14 days
e
control.
Positive
control:
enalapri
l, 2
mg/kg,
atenolol
10
mg/kg
of
systolic
pressure
by 12%
and 19%
after 3
and 6 h
each day.
Decrease
of
diastolic
pressure
by 34%
and 37%
after 3
and 6 h
each day.
Cumulati
ve affect
after 10
days.
va,
Makaro
v, 2010
120
Table 5. Summary of Pharmacological Studies for A. incana
Activity
Model
Pla Extract Admi Dosa Control
tested
used
nt
type
n
ge/
par
durat
t
ion
use
d
Negative
200,
Cat MeOH 96
Anticance In vitro,
control.
100,
kins extract, well
r
Positive
50,
soxhlet plate
control:
25,
with
Human
Cisplatin
and
381.3±7
cervix
12.5
.2 mg
adenocarci
g/m
gallic
noma
L,
acid
HeLa cell
equival
ents/g
extract
Negative
1
Cat Polyphe Per
In vivo
Antioral
mg/k control
kins nolic
inflammat Rats,
g, 30
extract
ory
chloroquin
days
(ellagic
e induced
and
irritation
gallic
of mucous
acid)
membrane
accompani
ed with
emotionalpainful
stress
Antiinflammat
ory
(photopro
tective)
Cat
In vivo.
kins
Guinea
pigs;
ultravioletinduced
erythema
AntiIn vivo.
inflammat Rats,
Cat
kins
Polyphe Intrag
astric
nolic
extract
(ellagic
and
gallic
acid)
1
mg/k
g, 40
min
befor
e and
2h
after
UV
irradi
ation
Polyphe Intrag
nolic
astric
1
mg/k
Results
Ref
ere
nce
IC50 = 39.9
g/mL
Stev
i et
al.,
201
0
Positive effect
on structures of
vessels of the
microcirculatory
bloodstream,
subepithelial
connective tissue
and
integumentary
epithelium of
tunica mucosa.
Effect by
endocellular
regeneration in
combination
with expressed
compensatory
hypertrophy of
part epithelium
integument cells.
Negative Decrease of
erythema (61%)
control.
accompanied
Positive
with decrease of
control:
methylura lipid conjugated
dienes and
cil, sea
buckthorn increase of
superoxide
oil
(39%)dismutase
and catalase
(16%) compared
to control group
Negative Decrease of
control.
malonyl-
Moi
seye
v et
al.,
200
8
Zvy
agin
tsev
a et
al.,
200
9
Myr
on121
extract
(ellagic
and
gallic
acid)
g, 40
min
befor
e and
durin
g 10
days
after
irradi
ation
Cat
Antimicro In vivo.
kins
bial
Newborn
rat.
Gastroente
rocolitis
induced by
Klebsiella
pneumonia
e
Polyphe Per
oral
nolic
extract
(ellagic
and
gallic
acid)
1.0,
2.5,
5.0,
10.0,
20.0
mg/k
g 14
days
Cat
Antimicro In vitro.
kins
bial
Broth
microdiluti
on
method
MeOH
extract,
Soxhlet
with ca.
381.3
mg of
gallic
acid
equival
ents/g
of
extract
ory
(radioprot
ective)
ionizing
radiation
of skin
(dose 80
Gy)
96
well
plate
No
data
dialdehyde and
lipid conjugated
dienes, increase
of antioxidant
enzymes activity
and quick
epithelization
and healing of
skin comparing
with control
group
Negative
Bacteriostatic
control
effect at 1.0 and
2.5 mg/kg (31.5
% and 62.5%
survival of rats
resp.)
Bactericidal
effect at 10.0
and 20.0 mg/kg;
100% survival
of rats.
No effect on
normal
microflora at
1.0-20.0 mg/kg
MIC = 0.117E. coli,
Salmonell 0.129 mg/mL
a
typhimuriu
m,
Enterobac
ter
cloacae,
Pseudomo
nas
aeruginos
a, P.
tolaasii,
Proteus
mirabilis,
Grampositive
Staphyloc
occus
aureus, S.
epidermidi
s,
Streptococ
cus
faecalis,
Bacillus
Positive
control:
methylura
cil
che
nko,
Zvy
agin
tsev
a,
200
8
Rik
alo,
200
5
Ste
vi
et
al.,
201
0
122
Antioxida
nt
Hepatopr
otective
catk
In vitro.
ins
DPPH
assay,
phospholip
id
degradatio
n
In vitro.
DPPH
assay
Cat
kin
In vivo.
Rats, CCl4
induced
hepatitis
Cat
kins
MeOH
extract,
Soxhlet
with
ca.381.
3 mg of
gallic
acid
equival
ents/g
of
extract
Crude
70%
aqueous
EtOH
(1:40,
w/v)
extract;
pedunc
ulagin,
glutinoi
n,
praecox
in D
Polyphe
nolic
extract
(ellagic
and
gallic
acid)
subtilis
Micrococc
us luteus,
M.
flavus,
Sarcina
lutea,
Listeria
monocytog
enes;
yeast:
Candida
albicans.
Negative
control,
streptomy
cin,
nystatin
Negative
control.
Positive
control:
Trolox
IC50 = 18.9
g/mL (DPPH),
IC50 = 48.6
g/mL
(phospholipid)
Ste
vi
et
al.,
201
0
In
vitro.
100
L
96well
micro
plate
10
mg/m
L
Negative
control.
Positive
control:
Gallic acid
Ascorbic
acid
IC50= 2.7±0.1
g/mL (crude
extract)
IC50 = 1.0±0.1
g/mL for
individual
compounds)
Iva
nov
et
al.,
201
2
Intrag
astric
1
mg/k
g
Negative
control.
Positive
control:
Carsil.
It limits
choleopoiesis
disorder, has an
antiinflammatory
and membrane
stabilizing
effect, recovers
physiological
Bun
iatia
n et
al.,
199
8
123
Hepatopr
otective
In vivo.
Rats
CCl4
induced
hepatitis,
ethanolinduced
hepatitis
Cat
kins
Polyphe Intrag
astric
nolic
extract
(ellagic
and
gallic
acid)
1
mg/k
g
Negative
control
antioxidant
system, increase
of bile secretion
and cholesterol
content in bile.
Repaired
functional
activity of
mitochondria to
the intact level
in ethanolinduced
hepatitis and
increased
microsome
hydroxylase
activity in CCl4
induced
hepatitis
Gor
dien
ko,
Yak
ovle
va,
199
9
124
Table 6. Summary of Pharmacological Studies for B. crassifolia
Activity Model
Plant Extract Admi Dosag Control
tested
used
part
type
n
e/
used
durati
on
9.0
Negativ
Leave Aqueous Per
Adaptog In vivo.
mL/kg e
infusion oral
s,
enic
Mice,
,
control.
black (1:10,
forced
7 days Positive
w/v),
swimming and
control:
ferme fingerpri
test.
nt by
nted
Rhodiol
a rosea
arbutin,
extract
bergenin
, ellagic,
gallic,
protocate
chuic
acids,
hydroqui
none.
Antican
cer
In vitro.
Human
lymphobla
stoid
Raji cells
Rhizo
mes,
green
leaves
Crude
EtOH
(40%)
extract
In
vitro
Antimic
robial
In vitro.
Liquid
dilution
method
Rhizo
mes,
leaves
EtOH
(80%)
extract
In
vitro.
Results
2 fold
Enhanced
swimming
time,
increased
glucose
utilization
and
decreased
lactate
levels
compared
to control .
Increased
fat
utilization
and a
decreased
body
weight of
15–18% in
groups
treated
with black
and
fermented
leaves.
10,
Positive 99%
50,
control: inhibition
200
methotr at 200
g/mL by
g/mL exate
fluorour rhizomes
extract;
acil,
cycloph 82%
inhibition
osphamide by leaves
extract.
,
vinblasti
ne.
Negativ
e
control
MIC
No
B.
(mg/mL)
data
cereus,
for
E. coli,
leaves/rhiz
P.
aerugin omes:
Referen
ce
Shikov
et al.
2010
Spiridon
ov et al.,
2005
Kokosk
a et al.,
2002
125
B. cereus:
62.50 /
15.63; E.
coli:
62.50/15.6
3; P.
aeruginosa
, 15.63/
62.50; S.
aureus:
62.50/62.5
0; C.
albicans:
250.00/
15.63
Positive Inhibition
control: production
predniso proinflamm
lone
atory Th1
cytokines
(IL-2, IFN and TNF).
Negativ Extract
normalized
e
control. content
Positive antibodycontrol: forming
enalapril cells in
spleen after
,2
stimulation
mg/kg,
atenolol by antigen
in both
10
immunode
mg/kg
pression
models.
Extract
decreased
expression
inflammato
ry
processes
under
delayed
hypersensit
ivity
reaction
conditions,
by
preventing
accumulati
on of T-
osa, S.
aureus,
C.
albicans
.
Positive
control:
erythro
mycin,
gentami
cin,
amphote
ricin B
AntiIn vivo.
inflamm Mice,
adjuvantatory
induced
arthritis
Not
specif
ied
Bergenin Per
(main
oral
coumari
ne) of
plant
5, 10,
20,
40, 80
mg/kg
In vivo.
Antiinflamm Mice,
immobiliza
atory
tion stress
or
cyclophosp
hamide
injections
Rhizo
mes
Per
Dry
oral
extract
standardi
zed by
arbutine
min
18%.
50
mg/kg
,
5 days
Nazir et
al., 2007
Churin
et al.,
2005
126
Antiobe
sity
In vivo.
Rats with
highcalorie
dietinduced
obesity
Leave
s,
black
and
ferme
nted
Per
Crude
aqueous oral
extract
standardi
zed by
arbutin,
bergenin
, ellagic,
gallic,
protocate
chuic
acids,
hydroqui
none.
Antioxi
dant
In situ.
DPPH
assay after
HPTLC
separation.
Leave
s,
green,
brown
,
black.
In vitro.
DPPH
assay.
Rhizo
mes
MeOH
extract,
with
arbutin,
bergenin
, ellagic,
gallic
acids,
hydroqui
none.
EtOH
(70%)
extract,
(+)-
50
mg/kg
,7
days
In
vitro.
1
mg/m
L
In
vitro.
10
mg/m
L
lymphocyte
s in the
inflammati
on focus
and
reducing
the ability
of cells to
produce
antiinflammato
ry
cytokines
Negativ Daily
dietary
e
control. intake
Positive reduced to
control: 40%
sibutram compared
with
ine
hydroch control.
Improveme
loride
nt in
glucose
tolerance
after 7 d
treatment.
Black
leaves
extract
reduced
serum
triglyceride
level by
45%
compared
to control
in rats.
Negativ ID50 (nmol)
e
gallic acid
control. 0.49;
Positive ellagic acid
control: 0.94;
ascorbic arbutin
acid
0.88;
hydroquino
ne 1.23.
Negativ
e
control.
Positive
SC50
(g/mL)
3.7 for
extract,
Shikov
et al.,
2012
Pozharit
skaya et
al. 2007
Ivanov
et al.,
2011
127
catechin
3,5-diOgallate,
(+)catechin
3-Ogallate
control:
gallic
acid,
catechin
,
2,6-ditertbutyl
-4methylp
henol
Negativ
e
control.
Positive
control:
(-)Catechi
n 3-Ogallate,
(-)Epicatec
hin 3-Ogallate
Antioxi
dant
In vitro.
Human
pancreatic
lipase
inhibition
Rhizo
mes
EtOH
(70%)
extract,
(+)catechin
3,5-diOgallate,
(+)catechin
3-Ogallate
96well
plate
25 L
Cerebro
protecti
ve
In vivo.
Hypoxia in
rats,
Leave
s
Dry
extract
Intrag
astric
300
mg/kg
,5
days
Negativ
e
control.
Positive
control:
piraceta
m
Immuno
stimulat
ing
In vivo.
Mice,
delayed
type
hypersensit
ivity
Green
leaves
Isolated Per
bergenan oral
–
polysacc
haride
comprise
2
mg/m
L in
drinki
ng
water
Negativ
e
control.
Positive
control:
apple
1.0 for (+)catechin
3,5-di-Ogallate,
1.3 for
(+)catechin 3O-gallate.
IC50
(g/mL)
3.4±0.2 for
extract,
0.42±0.04
for (+)catechin
3,5-di-Ogallate,
2.02±0.11
for
(+)catechin 3O-gallate.
Extract
prevented
the death of
rats which
occurred in
33-45%
cases of
control
group after
hypoxic
exposure.
Extract
exerted
cerebroprot
ective
effect by
preventing
inhibition
of the
succinate
oxidaze
system.
Increase of
DTH
reaction in
vivo.
Bergenan
enhanced
Ivanov
et al.,
2011
Khazan
ov,
Smirnov
a 2000
Popov
et al.
2005
128
Hypoten In vivo.
sive
SHR rats
ad
libitu
m (6
mg/da
y) 3
weeks
.
10 L
for
phago
cytic
activit
y.
50 L
for
perito
neal
cells
assay.
mainly
Dgalacturo
nic acid,
galactose
,
rhamnos
e,
arabinos
e,
glucose
residues;
appeared
to be
pectin.
(DTH)
reaction to
aggregated
ovalbumin
on
footpad
swelling.
In vitro.
phagocytic
activity of
human
blood
neutrophils
.
In vitro.
Mouse
peritoneal
cells.
Leave
s
Dry
extract.
Per
oral
50
mg/kg
,
14
days
pectin
uptake
capacity of
human
neutrophils
at 100
g/mL and
stimulated
generation
of oxygen
radicals by
mouse
peritoneal
macrophag
es in vitro.
Bergenan
increased
spontaneou
s
adhesion of
peritoneal
leukocytes
but did not
influence
adhesion
stimulated
by PMA or
adhesion of
peritoneal
leukocytes.
Negativ Decrease
of systolic
e
control. pressure by
Positive 20-25
control: mmHg
enalapril after 3-6 h
after each
,2
daily
mg/kg,
atenolol administrat
ion.
10
Decrease
mg/kg
of diastolic
pressure by
20-25
mmHg
after 1 h
each day.
Cumulative
effect after
7 days.
Makaro
va,
Makaro
v, 2010
129
Table 7. Summary of Pharmacological Studies for H. arenarium
Activity Model
Plant Extract
Admin Dosa Control
tested
used
part
type
ge/
used
durat
ion
100,
Aerial MeOH
Antibact In vitro,
Aeromon
In
as
50,
vitro.
extract,
erial
agar-well part
25,
Soxhlet
diffusion
hydrophil
a,
10
with
method
g/m Bacillus
gallic, pbrevis, B.
L
hydroxybe
cereus, B.
nzoic,
subtilis,
chlorogeni
E. coli,
c, caffeic,
syringic,
Klebsiella
pneumoni
pae,
coumaric,
ferulic,
Morganel
rosmarinic
la
morganii,
acids,
catechin,
Mycobact
epicatechi
erium
n, rutin,
smegmati
s, Proteus
resveratrol
mirabilis,
,
hesperidin
Pseudom
, apigeninonas
7aeruginos
a, S.
glucoside,
aureus,
eriodictyol
,
Yersinia
quercetin,
enterocoli
tica, C.
naringenin
albicans,
,
Saccharo
luteolin,
apigenin,
myces
and
cerevisiae
acacetin.
.
Positive
control:
amoxicilli
n, and 11
other
antibiotic
s.
Anticanc In vitro.
Aerial Methylene 96 well 10 g Positive
part
chloride
plate
per
control
er
Mouse
and
well
Methotre
leukemia
MeOH
xate
cells
extracts,
Negative
L1210,
soxhlet
control
Results
Refere
nce
No activity
against
E. coli, B.
subtilis, M.
morganii,
M.
smegmatis,
P.
mirabilis,
Y.
enterocolit
ica, S.
cerevisiae.
Inhibition
diameter
(mm at
100
g/mL): A.
hydrophila
(28.0), B.
brevis
(22.5), B.
cereus
(22.5), K.
pneumonia
e (17.0),
P.
aeruginos
a (28.0), S.
Aureus
(23.5).
Albayr
ak et
al.,
2010
96%
growth
inhibition
by
methylene
chloride
extract,
Goun
et al.,
2002
130
Anticoag In vitro.
ulant
Clotting
assays of
activated
partial
thrombop
lastin
time
(APTT)
and of
prothrom
bin time
(PT)
AntiIn vitro,
inflamm TNF-, 1
ng/mL
atory
induced
cytotoxic
ity in
L929
cells
Antioxid
ant
In vitro.
DPPH
assay,
reducing
iron(III),
H2O2:OH
–
luminol–
Flowe Crude
rs
extract
with
polypheno
licpolysacch
aride
fraction
In
vitro.
0.112.5
mg/m
L
Negative
control
Flowe MeOH
rs
extract,
50
constituen
ts
including
new
flavanone
and
chalcone
glycosides
named
arenarium
osides I,
II, III, IV.
96-well 3-100
microp M
late
Negative
control.
Positive
control:
sylibin,
piperine.
Infloresce
nces
In vitro
Crude
aqueous
infusion
(5g in 200
mL),
lyophilizat
es
(fingerprin
1
mg/m
L
Negative
control.
Positive
control:
silibinin
85%
growth
inhibition
by MeOH
extract
APTT >
600 sec at
12.5
mg/mL
and 479
sec at 6.25
mg/mL.
Pt 81.7 sec
at 12.5
mg/mL
20.8-40.7
%
inhibition
of TNF- induced
cytotoxicit
y in L929
cells at 30
M by
naringenin
7-O--Dglucopyra
noside,
apigenin
7-O--Dglucopyra
noside,
apigenin
7-Ogentiobiosi
de,
apigenin
7,4'-di-O-Dglucopyra
noside.
For
lyophilizat
es: IC50
=0.14 mg
(DPPH),
380-1049
asc. acid
equivalent
Pawlac
zyk et
al.,
2009
Morika
wa et
al.,
2009
Czinne
r et al.,
2000
131
microper
o-xidase
system
In vitro.
DPPH
assay,
phosphomolybde
num
method
t by TLC:
apigenin,
naringenin
,
kaempfero
l, luteolin,
quercetin,
caffeic
Acid,
helichrysi
n,
apigenin7-Oglucoside,
luteolin7-Oglucoside,
quercetin3-Oglucoside,
chlorogeni
c acid)
Aerial MeOH
In vitro
part
extract,
Soxhlet
with
gallic, phydroxybe
nzoic,
chlorogeni
c, caffeic,
syringic,
pcoumaric,
ferulic,
rosmarinic
acids,
catechin,
epicatechi
n, rutin,
resveratrol
,
hesperidin
, apigenin7glucoside,
eriodictyol
,
quercetin,
naringenin
,
luteolin,
s/mg,
IC90
=0.154 g
(H2O2/OH
luminolmicropero
xidase
system)
1
mg/m
L
Negative
control.
Positive
control:
butylated
hydroxytoluene,
ascorbic
acid
IC50 = 2348 g/mL
(DPPH)
106-162
mg asc.
acid
equivalent
s/g
Albayr
ak et
al.,
2010
132
In vitro.
Lipid
peroxidat
ion in
rats liver
microso
mes
Inflor
escence
s.
apigenin,
and
acacetin.
Lyophilize In vitro
d water
extracts
standardiz
ed by
polypheno
ls and
flavonoids
MDA
production
was
decreased
in 23-50%,
cytochrom
ec
reductase
activity
was
increased
in 20-50%
Virusatic
effect with
inhibition
zone 15-30
mm for all
viruses,
inactive
against
poliovirus
type 1.
0.010.02
mg/m
L
Negative
control.
Positive
control:
sylibin.
Herpes
virus
Hominis
HVP 75
(type 2),
influenza
virus A2
(Manhei
m 57),
Vaccini
virus,
poliovirus
type 1.
Negative
control.
Negative Hypotensi
control
ve effect
Flowe 10%
Antiviral In vitro.
rs
aqueous
Agar
extract
diffusion,
method.
HeLa
cells
Petri
dishes
0.02
mL
Hypothe
nsive
In vivo.
Rats,
dogs
Aerial Ether,
part
EtOH,
aqueous
extracts
Intrave
nous
Spasmol
ytic
In vivo.
Rats
Aerial Aqueous
part
solutions
of
naringenin
-5glucoside,
kaempfero
l-3glucoside)
, apigenin
dissolved
in
phosphate
Intrave
nous
50
mg/k
g
(dogs
),
500
mg/k
g
(rats)
4
mg/1
00 g
bw
50
mg/1
Negative
control.
Positive
control:
dehydroc
holic acid
Spasmolyt
ic activity
and
choleretic
effects
(approxim
ately
33% of
that of
dehydroch
olic acid)
for
individual
Czinne
r et al.,
2001
May,
Willuh
n, 1978
Szado
wska,
1962
Szado
wska,
1962
133
-buffered
sodium
hydroxide.
EtOH
extract
containing
all fl
avonoids
and
aqueous
extract
containing
no
flavonoids
.
00 g
bw
compound
s.
The
flavonoids
extract
demonstrat
ed
spasmolyti
c activity
similar to
individual
compound
s. The
flavonoids
free
extract
elicited a
spastic
response
in smooth
muscles
from rat
intestine
and gallbladder.
134
Table 8. Summary of Pharmacological Studies for T. vulgare
Activity Model
Plan Extract
Admi Dosage/
tested
used
t
type
n
duratio
part
n
used
10 g
Anticanc In vitro. Aeri Methylene 96
per well
well
chloride
al
er
Mouse
plate
leukemi part and
MeOH
a cells
extracts,
L1210,
soxhlet
Antihelm In vitro.
inthic
Egg
hatching
assay
(Ascaris
suum),
larval
migratio
n
inhibitio
n (L3
larvae
from
Trichost
rongylus
colubrif
ormis)
AntiIn vivo,
inflamm mouseear
atory
edema
induced
by 12-0tetradeca
noylphorbo
l 13acetate;
carragee
naninduced
mouse
Control
Results
Refere
nce
Positive
control
Methotrexa
te
Negative
control
99%
growth
inhibitio
n by
methyle
ne
chloride
extract,
95%
growth
inhibitio
n by
MeOH
extract
46%
ovicidal
effect on
A. suum
eggs at
2000
μg/mL;
49.5%
larval
migratio
n
inhibitio
n at
2000
μg/mL
Goun
et al.,
2002
93%
edema
inhibitio
n
ID50=0.
18
mol/ea
r by
parthen
olide;
92%
inhibitio
n by
chlorofo
rm
Schinel
la et
al.,
1998
Aeri
al
part
EtOH
(80%)
extract.
96
well
plate.
62.52000
μg/mL
Negative
control.
Positive
control:
albendazole
Aeri
al
part
Dichlorme
thane,
MeOH,
chlorofor
m
extracts;
parthenoli
de,
methoxyfl
avones
jaceosidin,
eupatorin,
chrysoerio
l,
diosmetin.
Topica
l
applic
ation
in ear.
Per
oral.
0.5mg/e
ar
100
mg/kg
per oral
Negative
control.
Positive
control:
indometacin
,
phenylbutaz
one
Urban
et al.,
2008
135
paw
edema
Antioxid
ant
In vivo,
Rats,
formalin
induced
edema
Inflo
rescen
ce
Polysacha
ride
complex
(ammoniu
m oxalate
extract)
Intraga 0.3 g/kg,
stric
7 days
In vitro.
DPPH
assay,
Aeri
al
part
MeOH
crude
extract,
3,5-Odicaffeoyl
quinic
acid,
axillarin,
luteolin
In
vitro.
1
mg/mL
extract;
80%
inhibitio
n with
ID50=0.
50
mol/ea
r by
jaceosid
in.
24%
paw
edema
reductio
n after
1 h. by
parthen
olide.
61.9%
Negative
oedema
control.
inhibitio
Positive
n after 4
control:
indometacin h, 100%
inhibitio
.
n after 3
days of
treatme
nt.
Concent
ration
leucocyt
es and
erythroc
yte
sedimen
tation
rate was
equivale
nt to
control
group
after 7
days.
EC50=
Positive
control:
37μg/m
quercetin
L
(MeOH
extract);
IC50=9.
7 μmol
for 3,5O-
Kiriche
nko et
al.,
2012
JuanBadatu
ruge et
al.,
2009
136
Antithro
mbin
Antiviral
In vitro.
Thrombi
n
solution
from
bovine
plasma
In vitro,
antiviral
and
time-ofaddition
assay
96
well
plate
Aeri
al
part
MeOH
extracts,
soxhlet
Aeri
al
part
96
Crude
well
MeOH
plate
extract,
fractionati
on using:
petroleum
ether,
chlorofor
m, EtOAc,
BuOH,
water;
3,5-Odicaffeoyl
quinic
acid,
axillarin,
luteolin,
parthenoli
de.
50L
Negative
control
5-500
g/mL
Herpes
simplex
viruses
HSV-1,
HSV-2.
Positive
control:
acyclovir
dicaffeo
ylquinic
acid
Goun
87%
thrombi et al.,
2002
n
inhibitio
n
CE50 =
31.1
g/mL,
69.9
g/mL,
95.7
g/mL
for 3,5Odicaffeo
ylquinic
acid,
petroleu
m ether
and
EtOAc
extracts
respecti
vely
against
HSV-1.
CE50 =
42.7
g/mL,
47.0
g/mL,
58.4
g/mL,
61.1
g/mL
for
axillarin
, 3,5-Odicaffeo
ylquinic
acid,
EtOAc,
and
petroleu
m ether
extracts
Alvare
z et al.,
2011
137
Cholereti In vivo.
c
Rats,
CCl4
induced
hepatitis
Aeri
al
part
Tanaceholum®
Per
oral.
50, 100
mg/kg,
single
administ
ration
Negative
control.
Gastropr
otec-tive
Aeri
al
part
Chlorofor
m
extracts;
parthenoli
de
Per
oral.
2.5-80
mg/kg
(chlorof
orm
extract),
5-40
mg/kg
partheno
lide,
single
dose.
Negative
control.
In vivo.
Rats,
EtOHinduced
gastric
ulcer
respecti
vely
against
HSV-2.
Effect
in rats
treated
with 50
mg/kg
observe
d during
3 h.
After
administ
ration of
100
mg/g
bile
volume
increase
d 80.9%
after 1
h, and
76.2%
after 2
h.
Concent
ration of
bile
acids
increase
d in 2.7,
2.1 and
1.8 fold
compare
d to
control
after 1,
2, and 3
h.
100%
inhibitio
n of
damage
for
extract
(10
mg/kg)
and
parthen
olide
(40
Vichka
nova et
al.,
2009
Tourni
er et
al.,
1999
138
Immuno
modulatory
In vitro.
Activati
on of
NF-B;
NO,
ROS,
and
TNF-
producti
on.
Flo
wers
Polysacch
arides
with Mr =
326, 151,
64 and 9
kDa
96
well
plate
0-1600
g/mL
Negative
control.
Positive
control:
LPS.
mg/kg).
Adminis
tration
extract
(80
mg/kg)
or
parthen
olide
(40
mg/kg)
24 h
before
ethanol
treatme
nt
restored
numbers
mucosal
-SH
groups
to
values
near
controls
Xie et
Potent
macrop al.,
2007
hageactivatin
g
properti
es,
resultin
g in
modulat
ion of
NO,
ROS,
and
TNF-
producti
on.
Polysac
charides
stimulat
ed
neutrop
hil
MPO
release
and
activate
139
Spasmol
ytic
In vitro.
Rats
isolated
aorta
Aeri
al
part
Crude
aqueous
decoction,
lyophilize
d.
In
vitro.
50, 100,
200,
400, 800
g/mL
Negative
control.
In vitro.
Serotoni
n release
inhibitio
n.
Leav EtOH
es
extract,
parthenoli
de
In
vitro.
120024000
μg/mL
for
EtOH
extract;
1.146.04
M for
panheno
lide
Negative
control.
d NFB
signalin
g in
monocy
tic cells.
Biphasi
c
concentr
ationdepende
nt
relaxati
on: a
first
rapid
effect
within
10 min
after
addition
of
extract
(50
g/mL)
and
maximu
m at
200
g/mL,
which
relaxed
contract
ion by
about
30%
Serotoni
n
release
inhibitio
n with
IC50=
9797
μg/mL
fresh
weight
for
EtOH
extract
and
IC50=
3.03
Lahlou
et al.,
2008b
Marles
et al.,
1992
140
mol
for
parthen
olide
141
Table 9. Summary of Pharmacological Studies for L. palustre
Activity Model
Pla Extract
Adm Dosage/
tested
used
nt
type
in
duration
part
use
d
1/20Antibact In vitro.
Sho Aqueous In
erial
Broth
ots
extract
vitro 1/160
dilution
and
method.
isolated
polysacch
aride
complex
Anticanc In vitro.
er
Mouse
leukemia
cells
L1210,
Aeri
al
part
Methylen 96
e chloride well
and
plate
MeOH
extracts,
soxhlet
Anticanc In vitro.
er
Human
lymphoblastoid
Raji cells
Aeri
al
part
Crude
EtOH
(40%)
extract
In
vitro
Control
Tested
microbes
Staphyloc
occus
aureus, E.
coli,
Pseudomo
nas
aeruginos
a,
Klebsiella
pneumoni
ae
10 g per Positive
well
control
Methotrex
ate
Negative
control
10, 50,
200
g/mL
Positive
control:
methotrex
ate
fluorourac
il,
Results
Refere
nce
Bacteriost
atic effect
at 1/160
dilution,
excluding
to P.
aeruginos
a (1/20
dilution)
for
polysacch
aride
complex.
99%
growth
inhibition
by
methylene
chloride
extract.
This
extract is
not
attractive
as a
potential
source of
drugs
because of
the
possibility
of causing
necrosis
of the
cells.
71%
growth
inhibition
by MeOH
extract.
99%
inhibition
at 200
g/mL
Belous
ov et
al.,
2006
Goun
et al.,
2002
Spirido
nov et
al.,
2005
142
Antidiab
etic
Lea
In vitro.
ves
C2C12
murine
skeletal
myoblast
s and the
3T3-L1
murine
preadipoc
yte cell
lines
EtOH
(80%,
1:10)
extract
with
153.5
g/mg
total
phenolic
Antidiab
etic
In vitro.
Caco2/15
cells;
EtOH
(80%,
1:10)
extract
Lea
ves
In
vitro.
1.1
mmol/L
(glucose
deprivatio
n) or 150
mmol/L
glucose
(glucose
toxicity)
25-100
g/mL (in
vitro);
250
cyclophos
-phamide,
vinblastin
e.
Negative
control
Negative
control.
Positive
control
rosiglitazo
ne
Negative
control.
Positive
control:
Cytoprote
ctive
properties
under
conditions
of glucose
toxicity
and
glucose
deprivatio
n at 6.25
g/mL.
Exhibited
the effect
on the
basal and
insulin
stimulated
3Hdeoxyglucose
uptake in
differentia
ted 3T3L1
Adipocyte
s at
50 g/mL.
Triglyceri
de level
was
increased
by 3-fold.
Effect was
comparabl
e with
levels
induced
by10
mmol/L
rosiglitazo
ne
100
g/mL
instantane
ous
Harbila
s et al.,
2009
Nistor
Baldea
et al.,
2010
143
western
blot
analysis.
In vivo.
Rats, oral
glucose
tolerance
test
Antifung In vitro.
al
Microbroth
dilution
method.
Lea
ves
with
153.5
g/mg
total
phenolic
mg/kg (in
vivo)
Quercetin 96
3--D-(6- well
plate
pcoumaroy
l)
galactosi
de and
quercetin
3--D-(6phydroxybenzoyl)
100 L
inhibition
of
differentia
ted
Caco2/15
intestinal
cells
glucose
absorption
. Reduced
SGLT1
protein
expression
.
In vivo
reduction
AUC of
blood
glucose
levels
compared
with
control in
the
periods 0–
30 min,
0–50 min,
0–120
min
after
glucose
administra
tion.
Cryptococ MIC=16- Jin et
63 g/mL al.,
cus
1999
neoforma for C.
neoforma
ns,
Saccharo ns, S.
cerevisiae
myces
Cerevisia and A.
niger.
e,
Aspergillu MIC=
0.16-10
s niger,
g/mL for
Candida
albicans. amphoteri
cin B and
Positive
fluconazol
control
amphoteri e.
MIC=250
cin B,
fluconazol g/mL for
C.
e
albicans.
cytochalas
in B,
phlorizin,
phloretin.
144
Aqueous In
extract,
vitro
lyophilize
d.
0.2
mg/mL
(for
prostaglan
din)
0.25
mg/mL
(for PAF)
Ether oil
In
vitro.
37 Mol
Per
oral
50 mg/kg
/ Single
dose
In
vitro.
Not
indicated
Antiinflamm
atory
Aeri
In vitro.
Prostagla al
part
ndin
biosynthe
sis assay;
PAFinduced
exocytosi
s
Antiinflamm
atory
In vitro.
Prostagla
ndinsynthesiz
ing
cyclooxy
gena-se
system
from
sheep
seminal
vesicles
and
HPLC
separatio
n
Aeri
al
part
Antiinflamm
atory
In vivo.
Carragee
naninduced
edema in
rats
Shot Dry
s
extract
aqueous,
EtOH
40%,
EtOH
70%
Antioxid In vitro.
ant
DPPH
assay,
Fe3+EDTA-
Aeri
al
part
Essential
oil.
37
compounds
Moderate
inhibition
of
prostaglan
din
biosynthes
is (50%)
and
platelet
activating
factor
(PAF)induced
exocytosis
(71%)
Ether oil
Positive
inhibited
control:
cyclooxyg
eugenol,
carvacrol, enase in
vitro with
thymol,
guajazule 46.6% and
carvacrol
n,
was
urushiol,
curcumin, reported
to be one
piperin,
capsaicin, of the
compound
apiol,
s
cubebin,
isoalantol responsibl
e with
acton,
94%
ledol
inhibition.
However,
ledol, did
not inhibit
the
enzyme.
Negative, 51.5±4.6
%
Positive
inhibition
control:
butadione, of edema
50 mg/kg by EtOH
40%
extract,
comparabl
e to
butadione.
Negative
IC50=1.6
control.
g/mL in
DPPH
assay;
IC50=2.7
Negative
control.
Positive
control:
indometac
in,
eugenol,
quercetin,
saligenin.
Tunón
et al.,
1995
Wagner
et al.,
1986
Belous
ov et
al.,
2006
Kim,
Nam,
2006
145
H2O2
deoxyrib
ose
assay,
nonenzy
matic
lipid
peroxidat
ion of rat
liver
homogen
ate
50 L
Negative
control
88%
thrombin
inhibition
Goun
et al.,
2002
Shot Dry
s
extract
(EtOh
40%)
Per
oral
100
mg/kg /
Single
dose
Negative
control.
Belous
ov et
al.,
2007
Aeri
al
part
Singl
e
inject
ion
Not
indicated,
5-15 min
before
lethal
dose
Negative
control.
Extract
reduces
hexobarbit
al
sleeping
time in
1.4 (rats),
and 3.2
(mice)
folds.
Improves
functional
-metabolic
and
morpholo
gical
parameter
s of liver.
100% of
animals
survived
after a
dose of 6
Gy
Aeri
al
part
Radiopr
o-tective
In vivo.
Mice
irradiated
with irradiatio
n
g/mL in
Fe3+EDTAH2 O2
deoxyribo
se system;
IC50=13.5
g/mL in
nonenzym
atic lipid
peroxidati
on of rat
liver
homogena
te
96
well
plate
In vitro.
Thrombi
n
solution
from
bovine
plasma
Hepato- In vivo.
protectiv Rats,
mice,
e
CCl4
intoxicati
on
Antithro
mbin
identified
among
them
sabinene
(1617%),
terpinen4-ol
(7.6%),
myrtenal
(3.5%),
Selinene,
selinene,
elemene,
-caryophyllene
(2-6%
range)
MeOH
extract,
soxhlet
Combinat
ion of
Archange
lica
officinalis
and L.
Narima
nov et
al.,
1991
146
irradiation
palustre
extracts
In vivo.
30 days
albino
mongrel
male
mice
irradiated
with irradiatio
n
(LD90/30)
Aeri
al
part
Combinat
ion of
Archange
lica
officinalis
and L.
palustre
extracts
Singl
e
inject
ion
Not
indicated
Negative
control:
nonirradia
ted
animals
(LD50/30);
70%
survived
after a
dose of
7.5 Gy
(LD90/30),
and 25%
after a
dose of 8
Gy
(LD100/12)
by day 30.
Offspring Narima
nov,
were
1992
obtained
from 11 of
12
experimen
tal males.
The
number of
mouse
pups was
10.2 ± 0.6
and 7.4 ±
0.7 in
experimen
tal and
nonirradia
ted groups
respective
ly. The
number of
both sexes
in the
posterity
of
nonirradia
ted
parents
was equal,
in
offspring
of
experimen
tal groups,
the
number of
female
pups was
2.3 times
147
larger
than that
of males.
148
Table 10. Summary of Pharmacological Studies for T. farfara
Activity
Model
Plant Extract
Ad
Dosag
tested
used
part type
min e/
used
durat
ion
10 g
Aeria Methylene 96
Anticanc In vitro.
well per
l part chloride
er
Mouse
and MeOH plate well
leukemia
extracts,
cells
soxhlet
L1210,
Antiinflamma
tory
Antiinflamma
tory
Antimicr
obial
Control
Results
92%
growth
inhibition
by
methylene
chloride
extract.
71%
growth
inhibition
by MeOH
extract.
Negative, Inhibition
Positive
of
control:
arachidoni
G
N c acid
monometh metabolis
m and iyl -LNOS
arginine
(71.1%)
with IC50
=8.9 M.
Positive
control
Methotrex
ate
Negative
control
In vitro.
Murine
macropha
ge cell
line
(RAW
264.7),
lipopolysa
c-charideactivated
macropha
ges
In vitro.
Murine
macropha
ge cell
line
(RAW
264.7),
lipopolysa
c-charideactivated
macropha
ges
Flow
er
buds
96
Isolated
well
1,5 bisacetoxy- plate
8angeloylox
y-3,4epoxybisabola7(14),- 10dien-2-one
No
data
Flow
er
buds
Isolated
tussilagone
96
well
plate
0-30
M
Negative,
Positive
control:
zinc
protoporp
hyrin IX,
copper
protoporp
hyrin IX
In vitro.
Liquid
dilution
method
Aeria EtOH
l part, (80%)
rhizo extract
me
In
vitro
.
No
data
B. cereus,
E. coli, P.
aeruginos
a, S.
aureus, C.
albicans.
Inhibition
of
production
of NO,
TNF-,
and PGE2
aswell as
i-NOS and
COX-2
LPSstimulated
RAW264.
7 cells and
murine
peritoneal
macropha
ges
MIC
(mg/mL)
for aerial
part/rhizo
me
B. cereus:
Refere
nce
Goun
et al.,
2002
Ryu et
al.,
1999
Hwang
bo et
al.,
2009
Kokos
ka et
al.,
2002
149
Positive
control:
erythromy
cin,
gentamici
n,
amphoteri
cin B
Negative
control.
Antioxida In vitro.
nt
Lipid
peroxidati
on in rat
brain
homogena
tes,
DPPH
assay.
Antioxida In vitro.
nt
DPPH
assay,
pyrogallol
autoxidati
on assay
Flow
er
buds
EtOAc
fraction
from
MeOH
extract
In
vitro
.
Not
indica
ted
Flow
er
buds
EtOAc,
In
BuOH,
vitro
aqueous
fractions
from EtOH
(70%
extract).
Main
compounds
:
chlorogeni
c and 3, 5Odicaffeoylq
uinic acids.
5-8
mg/m
L
Negative
control.
Antitussi
ve
Flow
er
buds
and
rachi
s
Aqueous
extract
Flowe
r bud
(2.8
g/kg),
rachis
(3.5
g/kg).
5
days.
Negative
control.
Positive
control:
pentoxyve
rine
In vivo.
Mice,
ammonia
induced
coughing.
Per
oral
16.63/62.5
; S.
aureus:
62.50/62.5
IC50=6.3
g/mL in
lipid
peroxidati
on assay,
IC50=14.3
g/mL in
DPPH
assay
EtOAc
and BuOH
fractions
exhibited
more
potent
activities
than
aqueous
fraction in
all tested
concentrat
ions. The
scavengin
g activity
of all
extracts
was found
in a
concentrat
iondependent
manner
After
treatment
with
flower
bud
extract
latent
period of
cough was
prolonged
in 47%
and cough
Cho et
al.,
2005
Li et
al.,
2012a
Li et
al.,
2012b
150
Expector
ant
In vivo.
Mice,
intraperito
neal
injection
of phenol
red
solution.
In vitro.
Neuroprotective Cortical
cell
cultures
Flow
er
buds
and
rachi
s
Aqueous
extract
Per
oral
Flowe
r bud
(2.8
g/kg),
rachis
(3.5
g/kg).
5
days.
Flow
er
buds
EtOAc
fraction
from
MeOH
extract
In
vitro
.
Not
indica
ted
frequency
was
decreased
in 48%
compared
to control.
Rachis
extract has
no
significant
effect.
Flower
Negative
bud
control.
enhance
Positive
tracheal
control:
ammoniu phenolsul
m chloride phonphthalein
excretion
in 42%
compared
to control,
indicating
strong
expectora
nt effect.
No effect
for the
rachis
extract
Negative
Inhibition
control.
of
neuronal
damage
induced
by
arachidoni
c acid
with IC50=
0.64
g/mL.
Attenuate
d
neuronal
damage
induced
by
spermine
NONOate.
Cell
viability
increased
Li et
al.,
2012b
Cho et
al.,
2005
151
to 30-40%
at 10
g/mL
and above.
Inhibited
A (25-35)induced
neurotoxic
ity with
IC50= 30.9
g/mL
and
glutamateor
N-methylD-aspartic
acidinduced
excitotoxi
city was
inhibited
with IC50=
76.3 and
53.7
g/mL
respectivel
y.
90% of
cells were
protected
from
Fe2+/ascor
bic acidinduced
damage at
30 g/mL.
H2O2induced
damage
was not
inhibited
until
300
g/mL.
Viability
of cells
exposed to
xanthine/
xanthine
oxidase
was
increased
152
at
30 g/mL
and above.
153
Table 11. Summary of Pharmacological Studies for I. helenium
Activit Model
Plant Extract type Admin
Dosag
y
used
part
e/
tested
used
durati
on
10,
Root Crude EtOH In vitro
Antican In vitro.
(40%) extract
50,
Human
cer
200
helenin (40%
lymphobla
g/mL
alantolactone
-stoid
and 60%
Raji cells
isoalantolact
one)
Root
In vitro.
Human
tumor cell
lines HT29, MCF7, Capan-2
and G1.
MTT
assay for
adherent
cell lines
and
propidium
iodide
staining
and FACS
analysis
for PBL
Acetone:
MeOH (2:1
v/v) extract
96 well
plate
10, 1,
0.1,
0.05,
0.01,
0.005
L/m
L
Contro Results
l
Positiv
e
control:
methotr
exate
fluorou
racil,
cyclop
hosphamid
e,
vinblas
tine.
Negati
ve
control
Negati
ve
control
100%
inhibition
at 50
g/mL by
EtOH
extract;
and at 10
g/mL by
helenin.
Helenin
exceeded
activity
cyclophos
phamide
and
fluorourac
il and
approache
d the
activity of
methotrex
ate.
Cytotoxic
effect
with LD50
(L/mL)
of 0.015
for HT29, of
0.017 for
MCF-7, of
0.020 for
Capan-2
and of
0.018 for
G1 and
LD90
(L/mL)
of 0.05 for
HT-29, of
0.20
for MCF7, of 0.10
for
Capan-2
and of
0.10 for
Refer
ence
Spirid
onov
et al.,
2005
Dorn
et al.,
2006
154
Antihel
mintic
Antihy
G1. The
cytotoxicit
y on
healthy
human
PBLs has
LD50 of
2.4- 3.0
(L/mL)
and
LD90=8.09.0
(L/mL)
Cytotoxici
ty over
100-times
higher in
tumor cell
lines than
in PBLs.
Positiv Athelmint Urban
62.5et al.,
ic effect
e
2000
g/mL control: on the egg 2008
albenda embryogenesis at
zole.
Negati 250-000
g/mL.
ve
control. LMI at the
dose of
125
g/mL
and
higher.
In vitro.
Egg
hatching
assay
(eggs
Ascaris
sum)
larval
migration
inhibition
(LMI)
(Trichostr
on-gylus
colubrifor
mis)
In vivo.
Rabbits
infected
with
Clonorchi
s sinensis
Rhiz
omes
and
roots
EtOH (80%)
extract
96 well
plates
Root
Boiled water
extract
In vivo.
In vivo.
Stem
Tincture
Injection 2.5
30
days,
begin
ning
at the
end of
3rd
day of
inocul
ation.
Negati Recovery
ve
rates of
control. worms
from
rabbits
was 2%.
Degenerat
ion,
atrophy,
necrosis,
dilatation,
etc. of
viscera of
the worms
was
observed
Negati Life-span
Rhee
et al.
1985
Zelen
155
poxant
Mice,
single
hemic
hypoxia,
repeated
hemic
hypoxia,
single
tissue
hypoxia,
repeated
tissue
hypoxia,
single
circulatory
hypoxia,
repeated
circulatory
hypoxia.
(1:10) by
EtOH 40%.
Contain
1.63% of
flavonoids,
dry residue >
2.25%
mL/kg ve
control
,
5 days
and 1
h
before
the
hypox
ic
expos
ure.
skaya
of mice
increased et al.,
2005
by 35%
after
single
hemic
hypoxia
and by
76% after
repeated
hypoxia.
Stressprotective
effect was
realized
through
prevention
of adrenal
hypertrop
hy and
splenic
involution
. The lifespan after
single
intoxicatio
n with
sodium
fluoride
was
prolonged
by 59%,
of those
exposed
to
repeated
hypoxia
by 29%.
Severity
of stress
decreased
by 5 and 4
points,
respective
ly,
compared
to control
due to the
protective
effect on
gastric
mucosa.
156
Antimi
crobial
In vitro.
Broth
dilution
assay
Root
Helenin (a
crystalline
mixture of
eudesmanoli
des)
In vitro.
In vitro.
Broth
microdilut
ion
method
Root
Stepwise
supercritical
fluid extract
(SFE),
hydrodistillate (HD).
Main
compounds:
Alantolactone,
isoalantolactone and elemene
In vitro.
The MIC
(g/mL)
against
several
strains of
S. aureus
was 10400, E.
coli and
P.
aeruginos
a 200750, C.
albicans 200-750.
Negati MIC
10from
ve
750
g/mL control. 0.009
Positiv mg/mL to
>14
e
control: mg/mL.
strepto HD and
mycin, SFE
bifonaz extracts
active
ole
against
Bacillus
cereus,
Staphyloc
occus
aureus,
Enterococ
cus
faecium
clinical
strain
resistant
to
ampicillin
,
erythromy
cin,
penicillin
and
tetracyclin
e
(MIC>0.0
3 mg/mL).
Candida
strains
were most
susceptibl
Negati
10ve
750
g/mL control.
Several
strains
of S.
aureus,
E. coli,
P.
aerugin
osa, C.
albican
s
Kowa
lewski
et al.,
1976
Deriu
et al.,
2008
157
In vitro.
Root
Radiorespi
rometric
bioassay
against
Mycobacterium
tuberculos
is
Isolated
alantolactone,
isoalantolact
one, 11H,
13-dihydroisoalantolactone
In vitro.
Antimi
crobial
Root
In vivo.
Mice
inoculated
with
Staphyloc
oc-cus
aureus
suspension
in the left
nare
Isoalantolactone
Subcuta
neously
Antiprolifer
ative
In vitro.
MK-1,
HeLa,
B16F10
cell lines,
MTT
assay
Root
MeOH
In vitro.
extract ,
isolated
1,3,11(13)elematrien8,12-olide,
igalan; 5epoxyalantol
actone; 4 ,
5 -epoxy1(10),11(13)germacradien
e-8,12-olide;
50
mg/kg
,2h
after
infecti
on
with
S.
aureu
s and
at 12h
interv
als
therea
fter
for a
total
of 6
doses.
e,
with
MIC=
0.0090.12
mg/mL.
MIC for
Negati alantolact
one and
ve
control. isoalantol
Positiv actone
was 32
e
control: g/mL.
encelin
from
Montan
oa
specios
a
Marked
Negati alleviation
of
ve
control: pulmonar
phosph y
inflammat
atebuffere ion;
d saline treated
mice less
accumulat
ion of
cellular
infiltrates
in alveolar
space.
Negati
ve
control.
Positiv
e
control:
5fluorou
racil
GI50 (M)
for 5epoxyalan
-tolactone
was 3.66.9, for
alantolact
one – 4.76.9.
1,3,11(13)
elematrien
-8,12-
Cantr
ell et
al,
1999
Qiu et
al.,
2011
Konis
hi et
al.,
2002
158
olide,
igalan
exhibited
almost the
same
potency,
but GI50
against
HeLa
cells was
2 folds
lower.
alantolactone, isoalantolactone, 11
,13-dihydroalantolactone, 11,13dihydroisoala
ntolactone
Antithr
ombin
In vitro.
Thrombin
solution
from
bovine
plasma
Not
speci
fied
Methylene
chloride
extract,
soxhlet
96 well
plate
50L
Negati
ve
control
100%
thrombin
inhibition
Goun
et al.,
2002
159
Table 12. Summary of Pharmacological Studies for P. caeruleum
Activity
tested
Model
used
Hypoglyc
emic
In vivo.
Mice,
glucose
tolerance
test.
Hypotensi
ve
Plant
part
used
Roots
with
rhizo
me
Extra Admin
ct
type
EtOH Intraperito
neal
70%
extract
with
65%
saponi
ns
Dosage/
duratio
n
10
mg/kg
In vivo.
Mice,
glucose
tolerance
test.
Roots
with
rhizo
me
EtOH Intraperito 10, 30
neal
mg/kg
70%
extract
with
65%
saponi
ns
In vivo.
Rabbits
with
experimen
tal
atheroscle
rosis
Roots
with
rhizo
me
Isolate Per oral
d
saponi
ns, no
details
Contr
ol
Results
Refere
nce
Negati
ve
control
.
Positiv
e
control
:
extract
of
roots
of Beta
vulgari
s
Glucose
concentra
tion in
the blood
decreased
by half in
30 min
after
glucose
injection.
Maximu
m of
glucose
in the
blood
was in 50
min after
injection.
Glucose
concentra
tion in
the blood
was
decreased
by half
after
injection
of 10
mg/kg of
extract in
30 min
after
glucose
injection.
Decrease
of
cholester
ol and
blood
pressure.
Accordin
g to
histologic
al
evaluatio
n,
saponins
Boyeva
et al.,
2007.
Negati
ve
control
.
Not
Negati
provided ve
control
.
Soroki
na et
al.,
2010.
Turova
, 1955
160
Sedative
In vivo.
Mice
exited
with
phenamin
e.
Roots Infusi
with
on
rhizo
me
Sedative
In vivo.
Rats,
prolongati
on of
soporific
effect of
sodium
ethaminal
Intragastri
Roots Dry
with
powde c
rhizo r
me
Per oral
0.010.03 g
(equival
ents of
dry
mass)
Negati
ve
control
.
Positiv
e
control
:
valeria
n
infusio
n
30, 60,
120
mg/kg
Negati
ve
control
.
Positiv
e
control
: V.
officin
alis
powde
r
reduce
lipid cell
infiltratio
n of the
aortic
intima
and large
vessels
Sedative
effect
was 8-10
times
stronger
compared
with
valerian
and more
pronounc
ed in
mice
exited
with
phenamin
e.
Combinat
ion of P.
caeruleu
m and V.
officinali
s (1:1, 60
mg/kg)
prolonge
d the
soporific
effect of
sodium
ethaminal
in 2.5
fold.
Zofina,
1946
Khisho
va et
al.,
2013
161
Table 13. Summary of Pharmacological Studies for V. opulus bark
Activity
Model
Pla Extract Admin
Dosage Contr
tested
used
nt
type
/
ol
part
durati
use
on
d
In vitro
0.4
No
Antispasmo In vitro. Bar MeOH
g/mL
data
k
extract
Single
dic
with
uterine
yield
horns
4%.
from
virgin
Holtzma
n rats
0.025- No
In vitro. Bar Isolated In vitro
k
scopolet
0.150
data
Single
in
mg/mL
uterine
horns
from
virgin
Holtzma
n rats
In vitro.
Barium
stimulat
ed rat
uterus.
Hypotensive In vivo.
Rats,
cats,
dogs.
Bar
k
Isolated
viopudi
al
In vitro
No
data
No
data
Bar
k
Isolated
viopudi
al
Intraveno
us
250
g/kg 2
mg/kg
Negati
ve
control
Results
Referen
ce
Complete Jarboe et
relaxation al., 1966
of muscle
at 1 mL
Relaxatio
n of
muscle
tension
and
spasms in
uterus,
IC50=0.09
mg/mL
ED50 for
spasmolyt
ic effect
24 g/ml
Jarboe et
al., 1967
In rats
hypotensi
ve effect
at 250
g/kg. At
1 mg/kg
effects
were
sustained
and
decrease
in blood
pressure
with
decrease
in heart
beat.
In dogs
and cats
effective
dose 2
mg/kg.
Nichols
on et al.,
1972
Nichols
on et al.,
1972
162
Table 14. Summary of Pharmacological Studies for C. cyanus
Activity Model
Plan Extract
Admin
Dosage/
tested
used
t
type
duratio
part
n
used
Intraperit 30, 60,
Flow WaterAntiIn vivo.
80
oneal
soluble
erinflamm Rats,
mg/kg;
topical
carrageen head ethanolatory
insoluble applicati 30 min
s
anbefore
polysacch on
induced
edema
arides
and
inductio
fraction
zymosann.
induced
100,
edema.
200,
Mice,
400 and
croton
800 g
oilper ear
induced
inflamma
tion of
ear.
Control
Results
Refere
nce
Negative
control.
Positive
control:
indomet
hacin,
acetylsal
icylic
acid,
Reductio
n of
carrageen
aninduced
edema by
40% at
30
mg/kg,
by 69%
at 60
mg/kg.
Reductio
n of
zymosaninduced
edema by
52% at
400 g.
Induced
the
formation
of an
anaphylat
oxin-like
activity
from 10
g/mL.
At higher
concentra
tions
(1000
g/mL),
reduced
haemolyt
ic
activity
of rat
serum.
Gastropr
o-tective
effect
was
100%,
89% and
83%
respectiv
Garbac
ki et al,
1999
In vitro.
Haemoly
tic
activity
of
complem
ent.
Anaphyla
toxin
activity
in rat
serum
Flow
erhead
s
Watersoluble
ethanolinsoluble
polysacch
arides
fraction
In vitro.
10, 50,
250,
1000
g/mL
(haemol
ytic)
0.01,
0.1, 0.5,
1, 5, 10
mg/mL
(anaphy
latoxin)
Negative
control.
Positive
control:
rosmarin
ic acid
Gastro- In vivo.
protectiv Rats
with
e
stressinduced
ulcer
(immersi
on and
Herb
,
flow
ers
Vegetal
product
(combinat
ion of
polysaccharides
and
polyphen
Per oral
500mg/
kg, one
h before
stress
Negative
control.
Positive
control:
ranitidin
e.
Antiinflamm
atory
Garbac
ki et al,
1999
Pirvu
et al.,
2012
163
ols
fractions)
immobilization
of rats
into cold
water, on
dorsal
position)
Diuretic
In vivo.
Dogs
with
chronic
fistula of
urinary
and gall
bladders.
Flow
erhead
s
Infusion
Intragastr No
(1:10) and ic
details
EtOH
extract
No
details.
ely, in
the
specific
case of
deep,
medium
and
superficia
l gastric
lesions,
respectiv
ely,
superior
to that of
ranitidine
(89%,
59%, and
54%
respectiv
ely on the
same
type of
lesions.
Stimulati Bashm
urin,
on of
diuresis
1951
and
choleresi
s.
164
Table 15. Summary of Pharmacological Studies for V. vitis-idaea
Activity Model
Plant Extract
Ad
Dosage/ Control
tested
used
part type
min duratio
used
n
Negative
25-100
Not
EtOH
Antidiab In vitro.
In
control.
indic (80%,
etic
Cacovitro g/mL
Positive
96- (in
1:10)
2/15
ated
control:
well vitro);
extract
intestinal
cytochala
plat 250
cells;
sin B,
mg/kg
e.
western
(in vivo) phlorizin,
blot
In
phloretin.
vivo
analysis.
per
In vivo.
oral
Rats, oral
glucose
tolerance
test
(OGTT)
Negative
0.2
Leav Aqueous
AntiIn
In vitro.
control.
extract,
inflamm Prostagla es
vitro mg/mL
Positive
(for
lyophilize
ndin
atory
prostagla control:
d.
biosynthe
indometa
ndin)
sis assay;
cin,
0.25
PAFeugenol,
mg/mL
induced
quercetin
(for
exocytosi
,
PAF)
s
saligenin.
Antiinflamm
atory
In vivo.
Mice,
acetic
acidinduced
vascular
permeabil
ity test.
Stem
s and
leave
s
EtOH
extract,
isolated
arbutin,
fraxin
Antimic
robial
In vitro.
Agar
dilution
assay,
Porphyro
monas
gingivalis
,
Prevotell
a
intermedi
a
Leav
es
Isolated
procyanidi
n B-1,
procyanidi
n, B-3,
proanthoc
yanidin A1,
cinnamtan
nin B1,
epicatechi
n-(
Results
Refere
nce
100 g/mL
instantane
ous
inhibition
glucose
absorption
inCaco2/1
5 cells.
In vivo No
effect in
OGTT.
Nistor
Baldea
et al.,
2010
Moderate
inhibition
prostaglan
din
biosynthes
is (45% )
and strong
inhibition
PAFinduced
exocytosis
(96% )
Negative Decrease
Per 5 g/kg
in vascular
oral. (extract), control.
permeabili
0.25g/kg Positive
, 0.5
control:
ty by
g/kg
dexameth fraxin (0.5
g/kg)
(arbutin, asone
similar
fraxin)
todexamet
hasone (1
g/kg).
0-100
Negative Epicatechi
In
n-(4-8)control.
vitro g/mL
epicatechi
Positive
.
n-(4-8,
control:
tetracycli 2-O-7)catechin,
ne
had strong
antimicrob
ial activity
against
Porphyro
monas
Tunón
et al.,
1995
Wang
et al.,
2005
Ho et
al.,
2001
165
Antimic
robial
In vitro.
Tube
dilution
assay,
eleven
strains of
Escherich
ia coli.
Leav
es
4-8)epicatechi
n-(4-8,
2-O-7)catechin,
epicatechi
n-(4-6)epicatechi
n-(
4-8, 2O-7)catechin.
Aqueous,
EtOAc,
EtOH
extracts
gingivalis
and
Prevotella
intermedia
with MIC
of 25
g/ml.
0-100
In
vitro g/mL
.
Negative
control.
Positive
control:
amoxicill
in
Leav
Antioxid In vitro.
ant
Anti-lipid es.
peroxidati
on
activity
(thiobarbi
turic acid
test).
Antisuperoxid
e
formation
: xanthine
oxidase
inhibition
test.
Free
radical
scavenger
activity:
cytochro
me C
test
Isolated
procyanidi
n B-1,
procyanidi
n, B-3,
proanthoc
yanidin A1,
cinnamtan
nin B1,
epicatechi
n-(
4-8)epicatechi
n-(4-8,
2-O-7)catechin,
epicatechi
n-(4-6)epicatechi
n-(
4-8, 2O-7)catechin.
No data
In
vitro
.
Negative
control
Antithro
mbin
MeOH
extract,
96
well
Negative
control
In vitro.
Thrombin
Not
speci
50L
MIC =
5mg/mL
for
aqueous
extract.
MBC=
5mg/mL
for nine
strains.
Cinnamtan
nin B1
strongest
anti-lipid
peroxidati
on activity
IC50=2.25
M,
proanthocy
anidin A-1
strongest
superoxide
scavenging
activity
IC50=10.14
M,
picatechin(4-6)epicatechi
n-(4-8,
2-O-7)catechin
strongest
antisupero
xide
formation
effect
IC50=308
M
94%
thrombin
Vu^i
et al.,
2009
Ho et
al.,
1999
Goun
et al.,
166
solution
from
bovine
plasma
In vitro.
Cells
infected
with
HSV-2.
XTT
assay.
Plaque
reduction
assay
fied
soxhlet
plat
e
Dried
whol
e
plant
s
Isolated
proanthoc
yanidin A1
96
well
plat
e,
24
well
plat
e
Coughsuppresa
nt
In vivo.
Mice, in
upset
beaker
saturated
with 25 %
NH4OH
Stem
s and
leave
s
EtOH
extract,
isolated
arbutin,
fraxin
Per 5 g/kg
oral. (extract),
0.25g/kg
, 0.5
g/kg
(arbutin,
fraxin)
Diuretic
In vivo.
Rats, 5
Leav
es
Infusion of Per 0.5
polyherbal oral. mL/100
Antivira
l
0.5-200
Mol
Negative
control.
Positive
control:
acyclovir
Negative
control.
Positive
control:
carbetape
ntane
citrate
Negative
control.
inhibition
2002
Proanthoc
yanidin A1 antiHSV-2
activity.
IC50=73.3
Mol for
XTT
assay.
IC50=41.9
Mol
IC90=62.8
Mol for
plaque
reduction
assay
100.0
Mol
proanthocy
anidin A-1
completely
suppressed
HSV-2
replication
when
added at
12 h postinfection.
Number of
coughing
decreased
43%,
latency
period
increased
53%
compared
to control
(EtOH
extract).
Effect of
fraxin (0.5
g/kg)simil
ar to
carbetapen
tane citrate
Increase of
diuresis in
Cheng
et al.,
2005
Wang
et al.,
2005
Vichka
nova et
167
Phlegm
removin
g
and 17 h
diuresis
with 5%
water
load
In vivo.
Mice,
injected
with
phenol
red
solution.
mixture
"Brusniver
"
Stem
s and
leave
s
EtOH
extract,
isolated
arbutin,
fraxin
g, 1
mL/100
g
Per 5 g/kg
oral. (extract),
0.25g/kg
, 0.5
g/kg
(arbutin,
fraxin)
Negative
control.
Positive
control:
NH4Cl
11.9%
comparing
to the
control
group.
Ethanol
extract and
fraxin (0.5
g/kg)
showed the
strongest
phlegmremoving
effect. The
phlegmremoving
effect of
arbutin
(0.5 g/kg)
was
similar to
that of
NH4Cl (1
g/kg).
al.,
1992
Wang
et al.,
2005
168
Table 16. Summary of Pharmacological Studies for Gemmae betulae
Activity Model
Plant Extract Admin
Dosage Control
tested
used
part type
/
used
durati
on
Buds Crude
10, 50, Positive
Anticanc In vitro.
In vitro
control:
EtOH
200
er
Human
(40%)
g/mL methotre
lymphoxate
extract
blastoid
fluorour
Raji cells
acil,
cyclopho
sphamide
,
vinblasti
ne.
Negative
control
10 g
Positive
Methyle 96 well
Not
Anticanc In vitro.
plate
per
control
speci ne
er
Mouse
chloride,
well
Methotre
leukemia fied
MeOH
xate
cells
Negative
extracts,
L1210
control
soxhlet
Antimicr
obial
In vitro.
Bacillus
subtilis,
Staphyloc
occus
aureus,
Escherich
ia coli,
Pseudom
onas
aeruginos
a.
Agar
diffusion
assay,
agar
dilution
assay.
Buds
Acetone In vitro.
extract
(1:5), reextracte
d with
MeOH,
decoctio
n (1:10)
0.0395%
Results
Referen
ce
63%
inhibitio
n at 50
g/mL
and 95%
inhibitio
n at 200
g/mL,
Spiridon
ov et al.,
2005
99%
growth
inhibitio
n by m
ethylene
chloride
extract
and 91%
growth
inhibitio
n by
MeOH
extract.
Negative Inhibitio
n zones
control.
Positive for
control: MeOH
ciproflox extract
and
acin,
gentamic decoctio
n were
in
sulphate, against
penicilli S.
n
aureus:
11.2 and
10.2 mm,
against
B.
subtilis:
11 and 8
mm,
against
P.
Goun et
al.,
2002
Duric et
al.,
2013
169
Antimicr
obial
Antioxid
ant
Buds
In vitro.
Agar
dilution
assay,
antibiotic
-resistant
forms of
144
strains of
Staphyloc
occi
isolated
from
patients
with
mastitis,
furunculo
sis,
abscesses,
peritonitis
.
Buds
In vitro.
DPPH
assay,
ABTS+
assay,
EtOH
(70%)
tincture
(1:5)
In vitro.
EtOH
extract
In vitro
aerugino
sa: 11.6
and 0
mm.
MIC for
MeOH
extract
against
P.
aerugino
sa:
1.25%,
against
B.
subtilis:
2.5%,
against
S.
aureus:
2.5%.
Negative Antibact
erial
control.
activity
was
observed
for all
strains
with
MIC in
dilution
1:901:100
0.011.0
mg/mL
Negative
control.
Positive
control:
trolox,
ascorbic
acid
IC50=0.5
11
mg/mL
in DPPH
assay,
IC50=0.2
90
mg/mL
in
ABTS+·
assay.
Nikolae
va,
Khokhl
ova,
1981
Mashent
seva et
al.,
2011
170
Antioxid
ant
Buds
In vivo.
Mice,
acute
hypoxia.
Phospholi
pids level
in brain.
EtOH
extract
Per oral
Diuretic
In vivo.
Wistar
rats, after
NaCl
solution
load (25
mL/kg)
Buds
6%
aqueous
extract
Intraperit
oneal
Heavy
metals
binding
In vivo.
Wistar
rats, feed
normal
diet with
additional
25 mg/kg
of Pb and
25 mg/kg
of Cd
during 10
days
Buds. EtOH
extract,
no
details
about
concentr
ation
and
method.
Per oral.
Negative Preventi
5.0
ve
mg/kg, control.
20 days Positive administr
control: ation of
tocopher extract
resulted
yl
in
acetate.
normaliz
ation of
phosphol
ipid
level.
Effect
was
compara
ble with
tocopher
yl
acetate.
1 mL
Negative Increase
of uric
per
control.
animal, Positive acid
control: eliminati
single
injectio furosemi on in 5
folds
n
d
comparin
g to
control
group
and
effect
was
similar
compare
d to
furosemi
d.
Negative The Pb
0.5
concentr
mL/kg, control.
ation in
32 days
animal
after 10
organs
days of
and
intoxic
tissues
ation
was
by
decrease
heavy
d by
metals
45.771.3%
and Cd,
by 10.492.2%
Mashent
seva et
al.,
2011
Peev et
al.,
2010
Bokova,
Vasil’ts
ova,
2011
171
compare
d with
control.
172
Table 17. Summary of Pharmacological Studies for A. vernalis
Activity Model
Plant
Extract Admin Dosage
tested
used
part
type
/
used
duratio
n
96 well 500
Aerial
MeOH
AntiIn vitro,
plate
L/mL
part
50%
inflamm human
extract.
whole
atory
blood
cell
culture
system
stimulate
d with
lipopolys
accharide activated
macroph
ages.
Petri
0.02
Aerial
10%
Antiviral In vitro.
mL
part
aqueous dishes
Agar
extract
diffusion,
method.
HeLa
cells
Cardiac
inotropic
and
constrict
or
In vivo.
Cats
Not
mentio
ned.
SCOA,
a
product
which
contains
extracts
from
Scilla,
Convall
aria,
Oleande
r and
Adonis
Intrave
nous
Control
Results
Negative
control.
Das et
35%
inhibition al.,
2007
TNF-
productio
n
Herpes
virus
Hominis
HVP 75
(type 2),
influenza
virus A2
(Manhei
m 57),
Vaccini
virus,
polioviru
s type 1.
Negative
control.
Positive
21.5control:
100
GPU/k cymarin,
g (GPU convallat
oxin,
=
guinea- proscillar
idin, and
pig
scillaren
units,
i.e.
cardiot
oxic
equival
ents
related
to 1 g
body
weight
Cytotoxic
effect
with
inhibition
zone 1530 mm,
virustatic
effect
with
inhibition
zone over
30 mm
for all
viruses,
Refere
nce
May,
Willuh
n,
1978
Lehma
Positive
inotropic nn,
1984
and
constricto
r effect
on veins
and
arteries.
Pure
glycoside
s
cymarin,
convallat
oxin,
proscillar
idin, and
scillaren
173
of
guineapigs)
exert
equal
effects.
Effect on
veins and
on the
heart may
differ for
the
glycoside
s tested.
Effect
equal
guineapig units
of
Adonis
extract on
capacitan
ce vessels
twice as
much as
Scilla,
Oleander
and
Convalla
ria
extracts.
Cymarin
(main
glycoside
of
Adonis),
has
stronger
effect on
veins
than
expected
from its
cardiotox
ic effect.
174
Table 18. Summary of Pharmacological Studies for Convallaria
Activit Model
Plant Extract
Admin Dosage/
y
used
part
type
duration
tested
used
5, 10, 20,
AntiIn vivo, Rhizo Convallama Per
oral
50, 100 g
roside, the
mes
tumor
Balb/c
of
steroidal
and
mice
convallam
induced roots saponin.
aroside / 3
by
days
human
kidney
tumor
cells
and by
sarcoma
L1 cells
Antivir
al
In vitro. Leave
s
Agar
diffusio
n,
method.
HeLa
cells
Cardia
c
inotrop
ic
In vivo,
beating
rabbit
atria
Aqueous
extract
(1:10)
Aerial Aqueous
part
extract
(1:5), dry,
convallatox
in
Control
Results
Negative Antitumo
control. r effect
on
human
kidney
tumors,
and
mouse
sarcoma
through
inhibition
angiogen
esis
Cytotoxi
Herpes
In vitro 0.02 mL
c effect
virus
Hominis with
HVP 75 inhibition
(type 2), zone 15influenz 30 mm,
virustatic
a virus
effect
A2
(Manhei with
inhibition
m 57),
Vaccini zone over
30 mm
virus,
polioviru for all
s type 1. viruses
Negative excludin
control. g
polioviru
s
Ex vivo 0.003; 0.03 Negative Extract
mg/mL for control. significa
ntly
extract and
increased
0.0001
atrial
mM for
stroke
convallato
volume,
xin
pulse
pressure,
and
cAMP
efflux.
and
markedly
increase
the K+
concentra
Refer
ence
Narto
wska
et al.,
2004
May,
Willuh
n,
1978
Choi
et al.,
2006
175
Cardia
c
inotrop
ic
In vitro. Not
Rabbit
specif
erythroc ied
ytes,
(Na+ +
K+)ATPase
, from
hog
cerebral
cortex
Cardia
c
inotrop
ic and
constri
ctor
In vivo.
Cats
Not
specif
ied.
Convallato
xin.
In
vitro.
Intrave
SCOA, a
nous
product
which
contains
extracts
from Scilla,
Convallaria
, Oleander
and Adonis
0.01 - 10
M
21.5-100
GPU/kg
tion in
the
beating
atriaderived
perfusate.
Convallat
oxin
increased
atrial
stroke
volume
and pulse
pressure
but did
not alter
the
cAMP
efflux
level.
Negative Inhibitio
control. n of
Positive palytoxin
control: -induced
ouabain, K+
digoxin, release
digitoxin with
.
IC50=0.9
M.
Inhibitio
n of
Na++K+
ATPase
with
IC50=0.8
4 M. No
inhibition
by
aglycone
s, even at
10 M
Positive Positive
control: inotropic
cymarin, and
convallat moderate
ly strong
oxin,
proscilla vasocons
trictor
ridin,
effect on
and
scillaren veins and
arteries.
Pure
Ozaki
et al,
1985
Lehma
nn,
1984
176
Cardiot In vivo. Leave
onic
Cats wit s
modulat
ed
ischemi
a
Tincture,
no details
about
preparation
Intrave
nous
Leave
s
Convara –
an aqueous
extract,
treated with
ferric
hydroxide,
concentrate
d under
reduced
pressure
until 1 g
was
equivalent
to 30 g of
dried
leaves.
Extract 0.1 g
direct
additio
n to the
Locke’
s
solutio
n.
Cardiot In vivo.
onic
Cats,
and
isolated
papillar
y
muscle
of the
cat
heart.
0.2 mL
glycoside
convallat
oxin,
exert
equal
effects.
Negative The
control. maximal
Positive increase
control: in the
tinctures amplitud
e of
of A.
vernalis, ischemic
Digitalis skeletal
purpure muscle
contracti
a,
ons and
Narium
oleander has lower
lethal
.
dose
comparin
g with
positive
control.
Negative Increased
control. strength
isometric
contracti
ons of
isolated
papillary
muscle.
Pardo
et al.,
1951
Weeks
,
Holck,
1943
177
Table 19. Summary of Pharmacological Studies for P. hydropiper
Activity Model
Pla Extract
Admin Dosage Control
tested
used
nt
type
/
par
duratio
t
n
use
d
Transd 1.7, 17, Negative
Fres Isolated
Anticanc In vivo.
170 nM control.
warburgan ermal
h
er
Mice
Positive
/ 1h
initiated spro al and
prior to control:
uts polygodial
with
Salicylal
each
7,12promoti dehyde
dimethyl
on with
benz
TPA
[]anthra
cene
(DMBA)
and
promote
d with
12-Otetradeca
noylphorbol13acetate
(TPA)
Negative
Antifertil In vivo.
Roo EtOH
Per
100control.
ity
Pregnan ts
(90%)
oral
200
cy rats.
extract
mg/kg/
single
dose
Negative
AntiIn vitro. Lea Commerci 96 well 0-200
g/mL control.
plate
ves al MeOH
inflamm Murine
extract
macroph
atory
(99%
age cell
purity)
line
(RAW
264.7),
lipopoly
saccharideactivated
macroph
ages
Results
Referen
ce
Delayed
the
formation
of
papilloma
s, and
markedly
reduced
rate of
papillomabearing
mice and
the
number of
papilloma
s per
mouse.
Matsum
oto,
Tokuda,
1990
66%
antifertilit
y in early
pregnancy
Prakash,
1985
Suppresse Yang et
al., 2012
d release
of NO,
TNF-,
and
prostaglan
din PGE2.
Inhibited
mRNA
expression
of proinflammat
ory genes
such as
iNO
synthase,
COX-2,
and TNF by
suppressin
178
Per
oral
Antiinflamm
atory
In vivo.
Mice
with
dextran
sulphate
sodium
(DSS)induced
colitis
Lea
ves
Commerci
al MeOH
extract
(99%
purity)
Antimicr
obial
In vitro.
Broth
microdil
ution
method.
Lea
ves
Confertifol In
in isolated vitro.
from
essential
oil.
100
mg/kg/
7 days
Negative
control,
DSS
Initial
concent
ration
0.5
mg/mL
Negative
control.
Positive
control:
fluconaz
ole,
ketocona
g the
activation
of NF-B,
activator
protein
(AP-1),
and cAMP
responsive
element
binding
protein
(CREB),
and
simultane
ously
inhibited
its
upstream
inflammat
ory
signaling
cascades,
including
cascades
involving
Syk, Src,
and
IRAK1
Extract
strongly
ameliorate
d the
DSSinduced
decrease
in colon
length that
had been
triggered
by
DSSinduced
colon
inflammat
ion
MIC
(g/mL )
was 1.56
against
Erwinia
sp, 6.25
against S.
Yang et
al., 2012
Duraipa
ndiyan
et al.,
2010
179
zole,
streptom
ycin
Antinoci
ceptive
In vivo.
Mice,
acetic
acidinduced
writhing
Aer
ial
part
Hexane,
EtOAc
MeOH
extracts
(yield
1.22, 1.81,
2.28% of
dried plant
material).
Per
oral
Antioxid
ant
In vitro.
DPPH
assay
Aer
ial
part
Hidropiper
oside B
and
vanicoside
sA
isolated
from
MeOH
extract
96 well No data
plate
In vitro.
Ferric
thiocyan
ate
method
Lea
ves
Isolated
7,4'dimethylq
uercetin,
3'methylque
rcetin
In
vitro.
Citotoxic
In vitro. Lea
Sensitize ves
d sheep
erythroc
250,
500
mg/kg,
0-10
ppm
Isolated
Microti No data
drimaneter
type
plates
sesquiterpe
Negative
control.
Positive
control:
aminopy
rine 50
mg/kg
Negative
control.
Negative
control.
Positive
control:
tocopher
ol
Negative
control.
aureus
and K.
pneumoni
ae, 7.82
against E.
floccosum,
C.
Lunata,
and
Scopulari
opsis sp.,
and 16.62
against T.
mentagrop
hytes and
T. rubrum
Suppressi
on of the
number of
writhing
in 1955%.
Maximal
effect for
EtOAc
extract at
500
mg/kg.
IC50 =
23.4
g/mL for
hidropiper
oside B,
26.7
g/mL,
for
vanicoside
s A.
ID50= 1.5
ppm for
4’dimethylq
uercetin
and 3.0
ppm for
3'methylque
rcetin.
Anticompl
ement
activity at
10.5
Rahman
et al.,
2002
Kiem et
al., 2008
Haraguc
hi, 1992
Fukuya
ma et
al., 1980
180
Estrogen
ic
ytes
and
guinea
pig
serum
(comple
ment)
In vivo.
Ovaryintact
and
ovariect
omized
(OVX)
rats
g/mL.
ne
dialdehyde
polygodial
.
Roo MeOH
ts
extract
Per
oral
1000
mg/kg /
12 days
Negative
control.
Positive
control:
estradiol17 (E2)
In uterine
tissues of
ovaryintact and
OVX rats,
extract
induced
hyperplasi
a in places
of luminal
epithelium
and
degenerati
on of
endometri
al glands.
In OVX
rats, the
effect of
extract on
uterine
endometri
um was
corroborat
ive with
the effect
of E2.
Hazarik
a and
Sarma,
2006
181
Table 20. Summary of Pharmacological Studies for A. graveolens
Activity Model Plan Extract
Admin Dosage Control
tested
used
t
type
/
part
duratio
used
n
Antibact In vitro Seed Aqueous, In vitro. 0.1 mL Negative
control.
s
hexane,
erial
Agar
Positive
EtOAc,
diffusio
control:
acetone,
n assay.
ampicillin,
EtOH
cefixime,
extracts
chlorampheni
col, cotrimoxazole,
gentamicin,
imipenem,
pipericillin/ta
zobactam,
tobramycin
Antibact In vitro. Aeri
erial
Microdi al
part
lution
assay.
E. coli,
P.
aerugin
osa,
Proteus
mirabili
s, K.
pneumo
niae,
Acineto
bacter
Essential
oil by
hydrodist
il-lation
Micropl
ates
No
data.
Results Referen
ce
Antibac
terial
activity
against
E.
faecalis
, S.
aureus,
E. coli,
P.
aerugin
osa, S.
typhi,
S.
typhim
urium,
S.
flexneri
with
MIC=5
-10
mg/mL
for
acetone
extract
and 2050
mg/mL
for
aqueou
s
extract.
MIC=1
Negative
-4
control.
g/mL
Positive
for al
control:
microb
ampicillin,
es
gentamicin,
(exclud
ofloxacin,
levofloxacin, ing
ketoconazole clinical
, fluconazole; isolates
) and 918
g/mL
for all
fungi.
Kaur
and
Arora,
2009
Erdoan
Orhan et
al.,
2012.
182
bauman
nii S.
aureus,
Enteroc
occus
faecalis
, B.
subtilis,
and
clinical
isolates.
C.
albican
s,
C.
parapsi
losis
Antibact In vitro. Not
speci
erial
Broth
dilution fied
method.
S.
aureus,
E. coli.
Antican
cer
In vitro. Aeri
Mouse al
leukemi part
a cells
L1210,
Commer
cial
essential
oil
96 well
plate
0-0.5%
(v/v)
Negative
control.
Methylen 96 well
e
plate
chloride
and
MeOH
extracts,
soxhlet
10 g
per
well
concent
ration
of the
extract
Positive
control
Methotrexate
Negative
control
300
mg/kg
Negative
control.
Positive
control:
AntiIn vivo,
inflamm Mice,
atory
formali
n
induced
inflam
mation
Aeri
al
part,
seed
s
Hydroalc
hoholic
extract
In vivo,
Rats,
formali
Fres
h
aeria
Sesame
oil
extract
Intraperit
oneal
morphine.
Topical 100
applicati mg/ 8
on on
days
Negative
control.
Positive
MIC(v/
v) =
0.37%
against
S.
aureus
and
0.47%
against
E. coli
98%
growth
inhibiti
on by
methyl
ene
chlorid
e
extract,
Analge
sic
effect
15-45
min
after
formali
ne
injectio
n by
both
extracts
.
Reduci
ng of
the paw
Delaquis
et al.,
2002
Goun et
al., 2002
RezaeeAsl et
al., 2013
Naseri et
al., 2012
183
l part (10:4)
n
induced
edema
paw
Antispa
smodic
In vitro. Seed
Rats
s
isolated
ileum
contract
ions
induced
by KCl,
acetylc
holine
and
BaCl2
EtOH
(70%)
extract
Direct
addition
of
extract
to the
media
with
ileum
0.1, 1,
2, 4
mg/mL
/cumul
ative
Antivira
l
In vitro, Aeri
antivira al
part
l
Essential
oil by
hydrodist
il-lation
96 well
plate
0.0250.8
g/mL
Diuretic
In vivo. Seed
Mongre s
l dogs.
EtOH
(70%)
extract.
Volatile
oil by
steam
distillatio
n.
Intraven
ous.
Volatil
e oil
0.004m
L/kg.
Extract
12.5,
25
mg/kg.
inflam
mation
even
stronge
r than
applicat
ion of
Diclofe
nac.
Negative
Maxim
control.
al
spasmo
lytic
effect
was for
BaCl2
induced
contrac
tion
with
IC50=0.
96
mg/mL
.
Antivir
Herpes
al
simplex
viruses HSV- activity
against
1,
parainfluenza HSV-1
type-3 (PI-3). at
0.025Positive
0.8
control:
g/mL
acyclovir,
and
oseltamivir
against
PI-3 at
0.4-0.8
g/mL.
Negative
Increas
control.
e in
urine
flow
2.2
folds at
12.5
mg/kg
no
effect
on
blood
pressur
e. 25
control:
diclofenac
gel 0.01%.
Gharib
Naseri,
Heidari,
2007
Erdoan
Orhan et
al.,
2012.
Mahran
et al.,
1991).
184
Gastrop
rotective
In vivo. Seed
s
Rats,
EtOH
and
HClinduced
gastric
ulcer
Aqueous
and
EtOH
(70%)
extracts
Per oral,
intraperi
toneal.
0.050.45
g/kg
aqueou
s
extract,
0.5-5
g/kg
EtOH
extract.
Negative
control.
Positive
control:
sucralfate,
cimetidine
mg/kg
produc
ed
a
further
but
insignif
icant
increas
e in
urine
flow
accomp
anied
by a
marked
hypote
nsion
that
lasted
for 1 h.
Volatil
e oil
increas
ed Na+
and Cl
excreti
on
Decrea Hossein
sed
zadeh et
gastric al., 2002
lesions
induced
by HCl
with
ED50=
0.12
g/kg
for
both
extracts
,
induced
by
EtOH
with
ED50=0
.34
g/kg
for
aqueou
s and
185
In vivo. Seed
s
Rats,
indome
thacin
induced
gastric
ulcer
after
ligation
of
pylorus.
In vitro
pepsin
binding
.
Dry
powder,
aqueous
and
EtOH
(95%)
extracts.
Per oral.
1.73
g/kg
for
EtOH
extracts
. Both
extracts
at
higher
doses
antisecr
etory
activity
as
effectiv
e as
cimetid
ine.
The
Negative
1, 1.5,
powder
control.
2 g/kg
of
Positive
of
seeds
powder control:
indomethacin dose
.
depend
Aqueou
ent
s and
decreas
EtOH
e
extracts
gastric
equival
acid
ent of 2
output,
g/kg of
increas
powder
e pH,
.
and
14
reduce
days.
gastric
ulcer
index.
Effects
of
aqueou
s and
EtOH
extracts
were
signific
ant but
lower.
Pepsin
binding
capacit
y of
powder
Rifat-uzZaman
et al.,
2004
186
Hypolip
idemic
In vivo.
Rats
fed
with
high
cholest
erol
(Chol)
diet,
rats
with
normal
diet.
Aeri
al
part
Essential
oil by
hydrodistillatio
n with phellandr
ene
(32%),
limonene
(28%)
and
carvone
(28%).
Dry
powder.
Per oral
Essenti
al oil:
45, 90,
180
mg/kg
for
high
Chol
diet
rats.
Dry
powder
: 10%
(w/w)
additio
n for
normal
diet
rats / 2
weeks
Negative
control.
Positive
control:
clofibrate
was
70.4%
at 0.5
g/mL.
Treatm
ent
with
essentia
l oil
resulted
in
dosedepend
ent
reducti
on of
total
Chol,
triglyce
ride
and
LDLChol
and
increas
e of
HDLChol
by 2433%.
Additio
n of
powder
reduced
the
total
Chol in
20%,
LDLChol in
2 folds
and
triglyce
ride in
14%
and
increas
ed the
HDLChol
concent
ration
Hajhash
emiand
Abbasi,
2008
187
Regulati
on of
menstru
al cycle
In vivo.
Rats in
estrus
phase
of
estrous
cycle.
Seed
s
Aqueous
and
EtOH
(80%)
extracts.
Per oral
Negative
0.045,
control.
0.45
g/kg of
aqueou
s and
0.5, 5
g/kg
EtOH
extracts
. 10
days
in 30%
compar
ed to
control.
Increas Monsefi
et al.,
e in
duratio 2006.
n of
estrous
cycle
and in
diestrus
phase
and
progest
erone
concent
ration
in high
dose
extract
treatme
nt.
188
Table 21. Summary of Pharmacological Studies for Rhizomata et radices Rubiae
Activity
tested
Model used
Antidiarrho In vivo.
eal
Rats, castor
oil-induced
diarrhea.
Mice, small
intestinal
transit.
Pla
nt
pa
rt
use
d
Ro
ot
Extract
type
Ad
min
Dosage/
duration
Control
Results
Refere
nce
Aqueous
extract,
12.5%
yield.
Per
oral
300, 600,
800
mg/kg /
single
dose
administr
ation.
Negativ
e
control.
Positive
control:
loperam
ide
Karim
et al.,
2010
No data
In
vitro
.
Protected
rats, in a
dosedependen
t fashion,
against
diarrhoea
l
dropping
by 3764%.
Inhibited
by 41%
the
gastrointe
stinal
transit of
charcoal
in mice at
800
mg/kg .
43%
inhibition
of
Trichoder
ma
viride,
41%
inhibition
of
Doratom
yces
stemoniti
s and
35%
inhibition
of
Penicilliu
m
verrucosu
m.
The
lesion of
mice
Antifungal
In vitro.
Disc
diffusion
method.
Ro
ot
MeOH
extract
with
6.3%
yield
Antileishm
aniasis
In vivo.
BALB/c
mice
Ro
ot
EtOH
Per
(80%,
oral
60, 40%)
No data.
Negativ
e
control.
Positive
control:
alizarin,
emodin,
parietin.
Negativ
e
control.
Manojl
ovic et
al.,
2005
Bafghi
et al.,
2008
189
infected with
leishmania
(L) major
[MRHO/IR/
75/ER].
extracts
Antilithiasi
s
Ro
In vivo.
Rabbits,
ot
foreign-body
bladder
calculus
model
Hydroxy
anthraqu
inone
derivativ
es
Per
oral
Antilithiasi
s
In vitro.
Ro
ot
5%
aqueous
solution
of
extract.
Kidney
In
vitro stone 20
mg
No
Ro
ot
Aqueous
, EtOH,
MeOH
and
EtOAc
extracts
10-100
In
vitro L in 6
mm disc.
.
Negativ
e
control.
Positive
control:
erythro
mycin
Antimicrob In vitro.
ial
Agar-disc
diffusion
method.
No data
No data
treated
with 40,
60 and
80%
extract in
water
were wet,
without
secondar
y
infection
and
necrosis.
Pronounc
ed
calciumcomplex
binding
effect and
reduction
in the
growth
rate of
the
calculi
After 15
days the
weight of
stone was
decreased
by 25%
and the
stone
structure
became
friable
Full
inhibition
of
Aspergill
us flavus,
Fusarium
oxysporiu
m, and
Streptom
yces
murinus
at 100
g/mL by
EtOH
and
MeOH
Berg et
al.,
1976.
Vichka
nova et
al.,
2009
Kalyon
cu et
al.,
2006
190
extracts.
191
Table 22. Summary of Pharmacological Studies for S. aucuparia fruits
Activity
tested
Model
used
Anticanc
er
In
vitro.
Mouse
leukem
ia cells
L1210,
AntiIn
inflamma vitro.
PPAR
tory
or
PPAR
activati
on in
human
embryo
nic
kidney
(HEK)
293
cells.
Antimicr In
obial
vitro.
Liquid
culture.
Antimicr
obial
Pla
nt
par
t
use
d
Fru
its
Extract
type
Ad
min
Dosage/
duration
Methylene
chloride
extract,
soxhlet
96
well
plate
10 g per Positive 98% growth
inhibition
well
control
Methotre
xate
Negative
control
Fru
its
Detannifie
d MeOH
extract
96
well
plate
10
g/mL
Negative
control.
Positive
control
GW7647
and
pioglitaz
one
Strong
activation
(75-100%) of
PPAR and
PPAR
Fru
its
Polypheno
l-rich
fraction
In
vitro
.
1 mg/mL
Negative
control.
Strong growth
inhibition of
Bacillus
cereus.
Bacteriostatic
effect against
Campylobacte
r jejuni and
Staphylococc
us aureus.
Weak
inhibition of
Salmonella
enterica, and
Escherichia
coli.
Inhibitory
effect on
hemagglutination of
E. coli HB101
(pRR7),
which
Fru
In
its
vitro.
Liquid
culture.
Inhibiti
on of
bacteri
al
hemagglutinat
ion
Polypheno In
l-rich
vitro
fraction
.
with
anthocyani
ns,
flavonols,
5caffeoylqu
inic and 3caffeoylqu
inic acids.
Control
Negative
1
control.
mg/mL.
0.5-2.0
g of
total
phenolics
/mL for
hemagglutinatio
n
Results
Refere
nce
Goun
et al.,
2002
Nohyne
k et al.,
2006
Kylli et
al.,
2010
192
Antioxid
ant
Antiproliferat
ive
2.1, 4.2, Negative
control.
8.4
g/mL of
phenolics
for
liposome
s.
25, 50,
and 100
g/g of
phenolics
for
emulsion
expresses the
M
hemagglutinin
.
In liposome
model 9097%
inhibition of
hexanal
formation; 6877%
inhibition
formation of
conjugated
diene
hydroperoxid
es.
In emulsion
oxidation
model 8695%
inhibition
hexanal
formation; 8087%
inhibition
formationconj
ugated diene
hydroperoxid
es.
The FRAP
value 61-105
M Fe2+/g of
fresh weight
and the DPPH
radical
scavenging
activity: 9.721 g of
berries/g of
DPPH radical.
Kylli et
al.,
2010
In
vitro.
Liposo
me and
emulsi
on
oxidati
on
assays.
Fru
its
Polypheno In
l-rich
vitro
.
fraction
with
anthocyani
ns,
flavnols,
5caffeoylqu
inic and 3caffeoylqu
inic acids.
In
vitro.
Ferric
reducin
g
antioxi
dant
power
(FRAP
).
DPPH
assay.
Fru
its
Acetone
(70%)
extracts of
fresh fruits
96
well
plate
30 L of
1/40
diluted
samples
for
FRAP
assay
and 50
L for
DPPH
assay
Negative
control.
In
vitro.
DPPH
assay.
Fru
its
In
vitro
.
0.5
mg/mL
Negative
control.
Positive
control:
trolox
35-53% of the
activity of
trolox taken
as100%
Zlobin
et al.,
2012
In
vitro.
HeLa
Fru
its
Water
soluble
polysaccha
rides
(yield
4.2%).
Polypheno
l-rich
fraction
96
well
plate
50
g/mL
Negative
control.
Reduced
viability of
HeLa cell to
McDou
gall et
al.,
Hukkan
en et
al.,
2006
193
cell
viabilit
y assay
50% of
control
2008
194
Table 23. Summary of Pharmacological Studies for I. obliquus
Activity Model
Plant
Extract Admin
Dosage/
tested
used
part
type
duratio
used
n
Antialler In vivo. Fruitin Aqueous Intraperit 0.1, 0.5,
extract
oneally
2.5,
gic
Mice
g
bodies
Per oral.
0.1, 1,
10
mg/mou
se
Antiastmathi
c
In vivo.
Asthmat
ic mice.
Sclerot
ium
EtOH
extract
Intraperit
oneally
Antican
cer
In vitro.
Mouse
leukemi
a cells
Not
specifi
ed
Methyle
ne
chloride
and
96 well
plate
Contro
l
Results
Negativ 100%
inhibition
e
control anaphylact
ic shock
induced by
compound
48/80 at
2.5 mg
Oral
administrat
ion
reduced
total IgE
levels and
slightly
affected
production
of IgG1.
Spleen cell
cultures
from
OVAsensitized
mice that
had
received
extract
orally
showed an
increase in
IFN-
No data. Negativ Inhibition
expression
e
control. of
phosphorp38
MAPK,
balancing
IFN-/IL-4
ratio and
decreasing
number
inflammat
ory cells
10
Positiv 100%
g/well e
growth
control: inhibition
Methot by
Refer
ence
Yoon
et al.,
2013.
Yan
et al.,
2011
Goun
et al.,
2002
195
Antican
cer
MeOH
extracts,
soxhlet
In vivo. Sclerot
ium
Mice
with
melano
ma.
In vitro.
Melano
ma B16F10
cells.
Aqueous
extract
Intraperit
oneally,
per oral
48 well
plates
Fruitin
g
bodies
Aqueous
extract
with
glucoserich
polysacc
harides
149 kDa
96 well
plate
Antidiab In vitro.
etic
3T3-L1
Preadip
ocytes.
Methylene
chloride
and 92%
by MeOH
extracts.
Initial
Negativ Intraperito
neal
concentr e
ation 50 control. administrat
mg/mL Positiv ion
reduced
e
control tumor
20
growth to
mg/kg/d
33% of
ay (i.p)
positive
200mg/
control.
kg/day
Inhibited
(p.o)
growth of
during
B16-F10
10 days
cells by
causing
cell cycle
arrest at
G0/G1
phase.
Negativ Extract
10, 25,
enhanced
50, 100 e
control. differentiat
g/mL
Positiv ion of
3T3-L1
e
control: preadipocy
insulin tes, and
dosedependent
increased
TG
accumulati
on. It
stimulated
gene
expression
of
CCAAT/e
nhancerbinding
protein
and
PPAR
during
adipocyte
differentiat
ion, and
induced
rexate
Negativ
e
control
L1210,
Youn
et al.,
2009
Joo et
al.,
2010
196
Antiinflamm
atory
Antiinflamm
atory
In vivo.
Acetic
acidinduced
abdomin
al
constrict
ion, hot
plate
tests in
mice.
Carrage
enaninduced
edema
in rats.
In vivo.
Mice
with
dextran
sulphate
sodium
(DSS)induced
colitis
Sporop
hores
MeOH
extract
(29.8%
yield)
Per oral
100,
200
mg/kg /
7
consecu
tive
days (in
rats),
100,
200
mg/kg
/single
dose in
mice
Fruitin
g
bodies
Aqueous
extract
Per oral
MeOH
extract
(29.8%
yield)
96 well
plate
50, 100
mg/kg /
twice a
day, 7
days
before
and
during
DSS
administration,
for 14
days.
Twice a
day 7
day
concurrent
with
DSS
administ
ration
45, 90,
135
g/mL
In vitro. Sporop
Murine hores
macroph
age cell
line
(RAW
the
expression
of PPAR
target
genes such
as aP2,
LPL and
CD36.
Negativ Dose
e
dependant
control. reduction
Positiv of paw
e
edema in
control: rats and
aspirin, analgesic
ibuprof activity in
en.
mice
Park
et al.,
2005
Negativ
e
control,
DSS
Diminishin
g colitis by
suppressin
g
expression
of
inflammat
ory
mediators
TNF-,
IFN-, IL1 and IL6, and
iNOS in
colonic
tissues.
Mishr
a et
al.,
2012
Negativ
e
control.
Positiv
e
control:
Inhibition
of iNOS
and COX2
expression
via the
Park
et al.,
2005
197
In vitro.
Ames
test
Sclerot
ium
Subfracti
ons from
MeOH
extract
Agar
plates
50 g
/plate
Antioxid In vitro.
ant
DPPH
assay
Sclerot
ium
Subfracti
ons from
MeOH
extract
In vitro.
5–500
g/mL
Antimut
agenic
downregulation
of NF-B
binding
activity
and
reduction
in nuclear
p65
protein
levels
Negativ Inhibition
of
e
control mutagenes
is induced
in
Salmonella
typhimuriu
m strain
TA100 by
the directly
acting
mutagen
MNNG
(0.4 g
/plate) by
77.380.0%.
Inhibition
of 0.15 g
/plate
4NQOinduced
mutagenes
is in TA98
and TA100
by 52.6–
62.0%.
Mutagenes
is in
TA100 by
Trp-P-1
and B()P
was
reduced by
70.5–
87.2%.
Negativ IC50 = 69
e
g/mL for
control. subfraction
Positiv 1
e
l-N6(1iminoet
hyl)
lysine
264.7),
lipopoly
saccharideactivate
d
macroph
ages
Ham
et al.,
2009
Ham
et al.,
2009
198
In vitro. Sclerot
ium
DPPH,
hydroxy
l
radicals,
superoxi
de anion
radicals,
H2O2
assays
In vitro. Fruitin
g
ABTS,
bodies
DPPH,
superoxi
de anion
radicals
assays
Immuno
modulat
ory
In vivo.
Balb/c
mice
Sclerot
ium
Polysacc In vitro.
haride
fractions
OP40,
IOP60,
IOP80
with
yield
2.2%,
11.6%,
0.84%,
Isolated
In vitro.
inonobli
ns A, B,
and C,
phelligri
dins D,
E, and G.
62.5–
1000
g/mL
Aqueous
extract
1–100
mg/kg/
up to 8
weeks
Per oral
No data
control:
ascorbi
c acid,
tocophe
rol,
BHA
Negativ
e
control.
Positiv
e
control:
ascorbi
c acid
Order of
reducing
power in
DPPH,
H2O2, and
hydroxylscavenging
activity
was IOP60
> IOP40 >
IOP80
Negativ Inonoblin
C was
e
control. most
Positiv active in
ABTS
e
control: assay (0.65
trolox, TEAC),
caffeic phelligridi
n D in
acid
superoxide
anion
radicals
assay
(IC50=85.5
M),
Phelligridi
n E in
DPPH
assay (1.57
TEAC)
Negativ Increased
in 1.5-3.5
e
control. fold the
proliferativ
e activity
of
splenocyte
s
transforme
d in vitro
by a
polyclonal
Con A
mitogen or
an
Du et
al.,
2013
Lee et
al.,
2007
Shash
kina
et al.,
2006
199
Immuno
modulatory
In vivo. Sclerot
Ovalbu ium
min
(OVA)sensitize
d
BALB/c
mice.
Ex vivo.
LPSstimulat
ed
peritone
al
macroph
ages.
Aqueous
extract
Per oral
Daily
50, 100,
200
mg/kg
alloantigen
in a mixed
culture of
lymphocyt
es
(MCL)
from
allogenic
mice
spleen.
Induced
formation
of
additional
T-killers in
the MCL.
8 weeks
administrat
ion
stimulated
cytotoxic
activity of
peritoneal
macrophag
es.
Negativ IgG2a was Ko et
e
suppressed al.,
2011
control. after the
second
immunizat
ion with
OVA.
ConA
stimulation
in spleen
cells
isolated
from
OVAsensitized
mice
treated
with 100
mg/kg
resulted in
5.2%
decrease in
IL-4
production
and a
102.4%
increase in
200
Radiopr In vivo.
o-tective Rats
irradiate
d with
cesium
(2.0 Gy)
Sclerot
ium
Chromog Per oral.
enic
complex
Radiopr In vivo.
o-tective Wistar
rats
Balb/c
mice irradiate
d (0.025
Sclerot
ium
Aqueous, Per oral
EtOH
extracts,
aqueous
suspensi
on
IFN-,
compared
to controls.
IL-4, IFN, and IL-2
were
reduced
after ConA
stimulation
in isolated
CD4+T
cells.
Extract
inhibits the
secretion
of NO
from LPSstimulated
peritoneal
macrophag
es ex vivo.
Negativ Between 3
4.0
and 10
e
mg/kg
/30 days control. days after
exposure,
recovery
of
hemopoieti
c tissue
function
and bone
marrow
cellularity.
Stimulatio
n of cells
participati
ng in the
immune
protection
of
neutrophils
(micropha
ges) and
lymphocyt
es.
Negativ Decrease
Dose
in the
e
not
indicate control. extent of
radionucli
d/ single
de
administ
deposition
ration in
in the bone
rats 2-3
Gavri
lov et
al.,
2003
Rasin
a,
2002
201
sGr/min
) 30
days.
min
after the
intraven
ous
injectio
n of 90Sr
isotope
irradiati
on.
30 days
administ
ration of
suspensi
on in
mice
and soft
tissues and
increase of
radionucli
de
eliminatio
n in 3335% in
rats.
Extension
of average
lifespan of
mice up to
305 days
(against
186 days
in the
untreated
control
group) and
prevented
a sharp
drop of
leukocytes
and lipid
peroxidati
on.
202
Table 24. Summary of Pharmacological Studies for Aralia
Activity
Model
Pla Extract
Admin
Dosage/
tested
used
nt
type
duration
par
t
use
d
Intragastr 16
Antiarrhyt In vivo. Ro Aqueous
ots extract
ic
mg/kg, 5
hmic
Rats,
days
coronar
y
occlusio
n and
reperfus
ion
Anticance
r
In vitro.
Human
kidney
Ro
ots
Isolated
araloside
A
In vitro
1, 3, 10,
30, 100
M
Control
Results
Refere
nce
Negativ
e
control
Improve
ment
heart
resistance
to
arrhythm
ogenic
effect of
ischemia
and
reperfusio
n.
86% of
animals
receiving
extract
before
coronary
occlusion
developed
no
arrhythmi
as, vs.
19% in
controls.
Severity
of
arrhythmi
a in
treated
rats was
74%
lower
during
ischemia
and
coronary
blood
flow
recovery
than
controls.
Reduction
of cellular
viability
Maslo
v et
al.,
2009
Negativ
e
control
Yu et
al.,
2011
203
cancer
cell
lines
GRC-1
and
786-O
Anticatara
ct
Anticatara
ct
Ex vivo.
Rat
lenses
from
male
Sprague
Dawley
rats.
Sugar
cataract
was
induced
by
adding
of (+)xylose
to
media
In vivo.
STZ-
Bar Aqueous
k
extract
with 7%
yield
24 well
plate
0.5, 1
mg/mL
Negativ
e
control
Bar Aqueous
k
extract
Per oral
300, 600
mg/kg
Negativ
e
of booth
cells in a
dose- and
timedependent
manner.
Number
of
Tunnelpositive
cancer
cells was
higher in
cells
treated
with
Araloside
A than
untreated
cells.
Araloside
A
increased
expressio
n of bax
mRNA
and
inhibited
expressio
n of bcl-2
mRNA.
Chung
After
treatment et al.,
2005
at 1
mg/mL
lens
opacity
was
lowered
by 36.4
and
31.3%
after 24
and 48 h,
respective
ly
After
treatment
Chung
et al.,
204
daily, 11 control
weeks
after
STZ
administ
ration
with 7%
yield
induced
diabetic
rats
Antiinflammat
ory
In vitro.
Murine
macrop
hage
cell line
(RAW
264.7),
lipopoly
saccharideactivate
d
macrop
hages
Ro
ots
Isolated
saponin
elatoside
F
96-well
plates
24-well
plates
Antiulcer
In vivo.
Aspirininduced
ulcer.
HClEtOH
induced
gastric
lesions.
Ro
ot
bar
k
Isolated
araloside
A
Per oral
with 300
or 600
mg/kg
extract
the
opacities
of lenses
decreased
by 15%
and 12%
respective
ly.
0.96, 9.6, Negativ Inhibition
of LPSe,
48, 96
Positive induced
M
control: NO
productio
tosyl
phenylal n in 28.8,
43.2,
anyl
chlorom 67.9, and
81.2% at
ethyl
ketone, 0.96, 9.6,
48, and
96 M.
Inhibition
of NF-B
activity in
20.4, and
33.7% at
48 M,
and 96
M
respective
ly.
50, 100
Negativ Reduction
of
mg/kg
e
control. HClPositive EtOHcontrol: induced
cimetidi gastric
lesions
ne.
and
aspirininduced
gastric
ulcers.
Antiulcer
action
may be
due to the
inhibition
of gastric
2005
Lee et
al.,
2009
Lee et
al.,
2005
205
Cardioprot In vivo.
ective
Cardiac
dysfunc
tion in
STZ
induced
diabetes
rats.
Ro
ots
Per oral
Total
aralosides,
no details
about
isolation.
4.9, 9.8,
19.6
mg/kg,
for 8
weeks
acid
secretion
Xi et
Prevents
diabetes- al.,
2009
induced
cardiac
dysfuncti
on by
increased
absolute
value of
left
ventricula
r systolic
pressure
and
maximum
rates of
pressure
developm
ent, and
enhanced
amplitude
of ICa2+-L
in cardiac
cells and
decreasin
g
connectiv
e tissue
growth
factor
expressio
n. High
dose, but
not low
prevented
cardiac
ultrastruct
ural
changes
in
diabetic
rats,
indicated
by closely
lining up
of
myofilam
ents and
almost
normal
206
Cardioprot In vtrvo.
ective
Injury
induced
by
H2O2, in
H9c2
cells
Ro
ot
bar
k
96-well
Waterplates
soluble
polysacch
aride
AEP-w1
(Mr
4.5×104
Da).
Monosacc
haride
componen
ts:
arabinogal
actan,
consisting
of
arabinose,
galactose
and trace
glucose
with
molar
ratios of
6.3:3.5:0.2
.
Gastroprot In vivo.
ective
Rats,
coldrestraint
stress
(CRS),
pylorus
ligation
Ro
ots
EtOH
(50%)
extracts
Intraperit
oneal
100, 200, Negativ
e
400
g/mL
control
50
mg/kg,
30 min
pretreat
ment
Negativ
e
control.
structure
of
mitochon
dria
AEP-w1
suppresse
d
cardiomy
ocyte
apoptosis,
the
mitochon
drial
membran
e
potential
change
and
cytochro
me C
release in
H2O2treated
H9c2
cells.
Intracellul
ar
reduced
glutathion
e (GSH)
reduction
caused by
H2O2 in
H9c2
cells was
restored
by AEPw1
pretreatm
ent.
Pretreatm
ent
reduced
incidence
and
severity
of
CRSinduced
gastric
glandular
lesions.
Zhang
et al.,
2013
Herna
ndez et
al.,
1988
207
Hypoglyc
emic
In vivo.
Rats,
glucose
toleranc
e test
(GTT)
Ro
ot
bar
k
Isolated
Per oral
oleanolic
acid and 9
oligoglyos
ides
100
mg/kg,
single
administ
ration
Negativ
e
control.
Hypoglyc
emic
In vivo.
Rats,
rabbits
with
high
choleste
rol diet.
Ro
ot
Saparal
(mixture
of
ammoniu
m salts of
aralosides
A, B, C)
Per oral
10, 23,
58
mg/kg, 3
days
(rats), 58
mg/kg
(rabbits)
Negativ
e
control.
Gastric
secretory
volume
was
reduced,
increased
intralumi
nal
gastric
pH and
decreased
acid
output.
3-Omonodes
mo-sides
elatosides
A and E,
stipuleano
-side R1
and
oleanolic
acid 3-Oglycoside
s showed
potent
inhibitory
activity in
GTT
Blood
serum
cholestero
l in rats
was
reduced
by 29.8%
comparin
g to
control at
58 mg/kg.
Level of
cholestero
l in the
aorta was
reduced
by 31.7%.
In rabbits
blood
cholestero
l was
reduced
by 61.4%.
Yoshik
awa et
al.,
1996
Voska
nyan et
al.,
1983
208
Table 25. Summary of Pharmacological Studies for R. roseae
Activity
Model
Plant Extract Admin Dosage/
tested
used
part
type
duratio
used
n
Roots Comme Intraga 10, 15,
Adaptoge In vivo.
stric
20
rcial
Mice,
nic and
mg/kg /
EtOH
forcedCNS
single
extract
swimming
dose
(contain
test,
ing 3%
swimming
rosavin
to
and 1%
exhaustio
salidros
n,
ide)
light/dark
exploratio
n, open
field, tailflick
Intraga 50
Rhizo EtOH
Adaptoge In vivo.
stric
mg/kg
me
(60%
nic
Rats,
/single
v/v)
exhaustiv and
dose
roots extract
e
with
swimming
3.02%
rosavin
es and
0.89%
salidros
ide
Anticance
r
In vitro.
Human
lymphobl
astoid
Raji cells
Antiarrhyt In vivo.
hmic
Rats,
isolated
heart.
Roots
Crude
EtOH
(40%)
extract
In vitro
Roots
EtOH
(40%)
extract
Per
oral
Control
Results
Negativ Induction
e control antidepres
sant-like,
adaptogen
ic,
anxiolytic
-like and
stimulatin
g effects.
Bell
shaped
doseactivity
curve
Negativ Prolonged
e control duration
of
swimmin
g (by
24.6%).
Activated
the
synthesis
or
resynthesi
s of ATP
in
mitochon
dria.
Positive 99%
10, 50,
control: growth
200
methotr inhibition
g/mL
at 200
exate
fluorour g/mL;
75%
acil,
cycloph inhibition
at 50
osphamide g/mL
with
,
vinblasti formation
of giant
ne.
Negativ polyploid
e control cells.
3.5
Negativ Preventio
mL/kg, 8 e
n
days
control, reperfusio
Positive n
control: arrhythmi
Refere
nce
Perfum
i and
Mattiol
i, 2007
Abidov
et al.,
2003
Spirido
nov et
al.,
2005
Maslov
et al.,
1997
210
Naloxon
e, ICI
174,864
Antiviral
Roots
In vitro.
Plaque
reduction
assay
In vivo.
BALB/c
mice,
SpragueDawley
(SD) rats
Coxsackie
virus B3
(CVB3)
Salidros Per
ide
oral
(purity
99%)
20, 60,
80
mg/kg /
7 days
Negativ
e
control.
Positive
control:
ribavirin
as and
elicitation
protective
effect in
experime
nts on
isolated
heart in
interrupti
ng the
perfusion
with
Krebs-Henseleit
solution
followed
by
reperfusio
n.
Antiarrhyt
hmic
effect was
mediated
through
activation
of opiate
receptors
in
myocardi
um.
Antiviral Wang
et al.,
effects
2009
both in
vitro and
in vivo.
Salidrosid
e
modulate
the
mRNA
expressio
n of
interferon
-,
interleuki
n-10 (IL10), TNF, and
interleuki
n-2 (IL2).
211
EtOAc
extract
EC50=
102.1
g/mL
against
H1N1 and
145.4
g/mL
against
H9N2.
Aqueous
extract
EC50=78.
5 g/mL
against
H1N1 and
139.7
g/mL
against
H9N2.
For
kaempfer
ol,
herbacetin
, and
rhodiolini
n
EC50=
30.2,
35.0, and
41.7 M
against
H1N1and 18.5,
23.0, and
29.3 M
against
H9N2.
70.4%
inhibition
of HIV-1
protease
Antiviral
Roots
In vitro.
Virusinduced
cytopathic
effect
(CPE) in
MadinDarby
canine
kidney
(MDCK)
cells
Viruses:
H1N1
(A/PR/8/3
4) and
H9N2
(A/Chicke
n/ Korea/
MS96/96)
.
Aqueou In
vitro.
s,
EtOAc
extracts
.
Isolated
kaempf
erol,
herbace
tin,
rhodioli
nin,
rhodion
in, and
rhodiosi
n
Initial
concentr
ation 5
mM
Negativ
e
control.
Positive
control:
oseltami
vir
(Tamifl
u)
Antiviral
In vitro.
HIV-1
protease
inhibition
Roots
MeOH
extract
In
vitro.
100
g/mL
Negativ
e
control.
Positive
control:
acetyl
pepstati
n
Hypotensi In vivo.
ve
SHR rats.
Roots
Aqueou
s
extract
with
Per
oral
35, 50,
75
mg/kg
Lee, et
Negativ Dosee control dependent al.,
2013.
decrease
systolic
Jeong
et al.,
2009
Min et
al.,
1999
212
Neurotrop In vivo.
ic
Mice,
thiopental
-induced
sleep
Roots
salidros
ide
(8.4mg/
g) and
ptyrosol
(1.9mg/
g).
EtOH
extract
blood
pressure
and
increase
endorphin
release.
Per
oral
10-500
mg/kg
Negativ Stimulatio Kurkin
et al.,
e control n at 10
2003
mg/kg
(sleep
period
reduced
by 12.5
times),
sedation
at 500
mg/kg
(sleep
period
was
increased
3-fold)
213
Table 26. Summary of Pharmacological Studies for Herba polygoni persicariae
Activit Model used
y tested
Antican
cer
In vitro.
Cervical
carcinoma
HeLa, acute
monocytic
leukemia
THP-1 cell
lines.Sulphor
hodamine B
cell growth
inhibition
assay
Antifun
gal
In vitro.
Microbroth
dilution
assay.
Candida
albicans,
Saccharomyc
es cerevisiae,
Cryptococcus
neoformans,
Aspergillus
flavus, As.
fumigatus,
As. niger,
Trichophyton
rubrum, Tr.
mentagrophyt
es,
Microsporum
gypseum
Pla
nt
par
t
use
d
Aer
ial
par
t
Extract
type
Aer
ial
par
t
Admin
Dosage
/
duratio
n
Control Results
96 well
Isolated
cardamom plate
in,
pinostrobi
n
1, 10,
30, 50,
100
g/mL
Negativ
e
control.
Positive
control:
paclitax
el
In vitro.
Dichloro
methane
extract.
Isolated
polygodia
l,
isopolygo
dial, and
cardamoni
n.
Initial
concent
ration
100 L
Negativ
e
control.
Positive
control:
retocon
azole,
amphot
ericin,
terbinaf
ine
For
cardamo
min IC50
= 1.8
g/mL
against
THP-1
and 17
g/mL
against
HeLa. For
pinostrobi
n IC50 = 9
g/mL
against
THP-1
MIC
(g/mL )
for
dichloromethane
extract
was 31.2
against
Tr.
Mentagro
phytes;
polygodia
l 3.9
against C.
albicans,
7.8
against C.
neoforma
ns, Tr.
rubrum,
Tr.
Mentagro
phytes,
and 15.6
against S.
cerevisiae
;
cardamon
Refer
ence
Dzoy
em et
al.,
2012
Derita
,
Zacch
ino,
2011
214
Antiinflam
matory
In vivo.
Carrageenaninduced
edema in rats
Aer EtOH
ial extract
par
t
Intraperi
toneal
Not
provide
d
Negativ
e
control.
in 15.6
against
Tr.
rubrum,
and Tr.
mentagro
phytes
Yano
Antiinflammat et al.,
2011
ory
activity.
215
Abstract
Ethnopharmacological relevance: Due to its location between West and East, Russian
phytotherapy has accumulated and adopted approaches originating in European and Asian
traditional medicine. Phytotherapy is an official and separate branch of medicine in Russia and
thus herbal medicinal preparations are official medicaments. The aim of the present review is to
summarize and critically appraise the data concerning plants used in Russian medicine. This
review describes the history of herbal medicine in Russia, current situation and pharmacological
effects of those specific plants of Russian Pharmacopoeia which are not included in European
Pharmacopoeia.
Materials and methods: Based on the State Pharmacopoeia of the USSR, 11th edition we selected
plant species which have not been adopted yet in Western and Central Europe (e.g. via the
inclusion in the European Pharmacopoeia) and systematically searched the scientific literature
for data through library catalogs, the online service E-library.ru and in addition
Medline/Pubmed, Scopus and Web of Science databases on the species, effectiveness,
pharmacological effects and safety.
Results: The Russian Federation follows the State Pharmacopoeia of the USSR, 11th edition
which contains 83 individual monographs for plants. Fifty one plants are also found in the
European Pharmacopoeia and have been well studied, while 32 plants are only found in the
Pharmacopoeia of USSR. Many articles about these medicinal plants were newer translated in
English and a lot of information collected by Russian scientists was not available for
international community. Such knowledge can be applied in future studies aiming at a safe,
evidence-based use of traditional Russian medicinal plants in European and global
phytopharmacotherapy as well as for the discovery of novel leads for drug development.
Conclusion: The review highlights the therapeutic potential of these Russian
phytopharmaceuticals, but it also highlights cases where concern is raised about the products
safety and tolerability and that would support their safe use.
216
graphical abstract