International Journal of Complementary & Alternative Medicine
Research Article
Open Access
The different roles of Griffonia simplicifolia in the
treatment of depression: a narrative review
Abstract
Volume 14 Issue 3 - 2021
Introduction: Several studies have demonstrated the importance of some plants for the
treatment of depression because they are sources of 5-hydroxytryptophan (5-HTP), among
them, Griffonia simplicifolia stands out, especially when dosed and formulated as an herbal
remedy.
Renata de Melo Guerra Ribas,1 Diélita
Carla Lopes de Oliveira,1 Paulo César
da Silva,1 Hugo André de Lima Martins,1
Joyce Gomes de Moraes,1 Mayara Paula da
Silva,1 Valdenilson Ribeiro Ribas,1 Clenes
de Oliveira Mendes Calafange,2 Ana Elisa
Toscano Meneses da Silva Castro,2 Raul
Manhães de Castro2
Objective: The purpose of this article is to conduct a narrative review on the treatment of
depression through the phytotherapic Griffonia simplicifolia.
Method: A bibliographic review and a search of the electronic index databases MEDLINE/
PubMed, Web of Science, CAPES journal portal, BIREME and Google Scholar were
carried out.
1
Brain Institute of Pernambuco (ICerPE), Brazil
Postgraduate Program in Neuropsychiatry and Behavioral
Sciences (Posneuro), Brazil
2
Results: Phytotherapy is only equivalent to allopathy only in the use of the law of the like.
However, its substances come only from vegetable origin. Thus, unlike allopathic drugs,
it cannot be called a drug, but an active principle. Thus, both allopathy and phytotherapy
agree to increase the availability of 5-HT in the treatment of depression. In this sense, among
these medicinal plants tested in the laboratory, this study chose Griffonia simplicifolia that
presents pharmacodynamic conditions for the treatment of depression because it is a source
of 5-hydroxytryptophan (5-HTP). Research has shown that Griffonia simplicifolia extracts
increase the level of serotonin in the brain. Each seed is estimated to contain about 6 to 14%
of 5-HTP. In some countries, after an industrial extraction, the researchers combine the
contents of several seeds to provide 95-98% of 5-HTP in each capsule.
Correspondence: Valdenilson Ribeiro Ribas, Senador Sérgio
Guerra, 220, Apt. 132, Piedade - Jaboatão dos Guararapes,
Tel 54.400-003, Email
Received: May 22, 2021 | Published: June 09, 2021
Conclusion: The studies presented in this narrative review demonstrate that 5-HTP
extracted from Griffonia simplicifolia can be effective in the treatment of fibromyalgia,
chronic headaches, insomnia, in the anxiety control and, above all, in depression.
Keywords: phytotherapy, griffonia simplicifolia, depression
Introduction
plants used today are from India, such as: nutmeg, pepper, cloves,
among others.1
Medicinal plants - historical aspect
The oldest recorded entry on the use of medicinal plants for the
purpose of making a pharmacological compound for the treatment of
diseases was found on a chalkstone, from approximately 3000 BC,
from the ancient Sumerian civilization in Nagpur, a city in India,
in the state of Maharashtra.1,2 In this registry, 12 formulations were
found for the organization and preparation of drugs consisting of more
than 250 different herbs.
There are reports in the literature that put the Egyptian civilization
in this dispute for the pioneering of the discoveries of medicinal
plants, dating from 6000years ago, approximately 4,000 BC, however,
it includes, in addition to plants, products of animal origin.3
Then, this dispute approaches, the Chinese book on roots and
grasses, written by Emperor Shen Nung around 2500 BC, which
discusses about 365 medicinal substances, derived from the dry parts
of different plants and, at the same time, the encyclopaedia of the days
Chinese medical material published in 1977 registered almost 6000
medicinal substances, of which 4800 are of plant origin.1
The use of medicinal plants was also widespread among the
peoples of India, around 2000years ago.4 The Indian sacred books,
Vedas, composed in a language called Vedic Sanskrit, mention the
treatment with plants, which are abundant in that country. Many spice
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Int J Complement Alt Med. 2021;14(3):167‒171.
The peoples of Mexico and Central America, the Aztecs, have been
exploring the effectiveness of medicinal herbs for at least 1000years,
even referring to treatments for simple diseases, such as acne, even
the most complex, such as epilepsy.3
In ancient history, the most relevant record on plant drugs
was prepared by the Greco-Roman author, Pedânio Dioscórides,
considered the founder of pharmacognosy, who, as a military doctor
and responsible for pharmacology in Nero’s army, studied medicinal
plants. Around 77 AD, he wrote a work,5 divided into 5 books, where,
of the total of 944 drugs described, 35 drugs were of animal origin,
90 of mineral origin, of which only about 130 already appeared in the
Corpus hippocraticum and 657 were of vegetable origin.1
The great strength and the first leap, which made it possible to
study the effects of medicinal plants, was given by a Swedish botanist,
zoologist and physician, Carolus Linnaeus, creator of binomial
nomenclature and scientific classification, considered the founder of
modern taxonomy, who documented and classified in a standardized
manner thousands of botanical species about medicinal plants in the
18th century. Species Plantarum was first published in 1753 in two
volumes.6
Anyway, there are several studies that address the effects of
medicinal plants on diseases that affect the liver, kidneys, stomach,
167
©2021 Ribas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which
permits unrestricted use, distribution, and build upon your work non-commercially.
The different roles of Griffonia simplicifolia in the treatment of depression: a narrative review
intestines, among others. However, due to the complexity surrounding
the central nervous system, the most surprising studies are the findings
that involve the effect of the treatment of various mental illnesses,
including depression through some plants, which are sources of
5-hydroxytryptophan (5 -HTP).7
Serotonergic neurotransmission and depression
The synthesis of the neurotransmitter 5-hydroxytryptamine or
cerebral 5-HT serotonin occurs in the central nervous system, from
the essential amino acid L-tryptophan8 and depends on the nutrition
and balance of the intestinal microbiota.9
However, when it comes to nutrition biochemistry, it seems relevant
not to think in a reductionist way, because it is not an isolated effect,
but a complex process that involves the interaction of several nutrients,
such as: vitamin B6, in the form of pyridoxal-5-phosphate, because it
is water-soluble, acts on the biosynthesis of 5-HT, transporting atoms
and electrons in the decarboxylation process, folic acid (vitamin
B9) and cobalamin (vitamin B12)10 in the transmethylation process
for control of the number of neurotransmitters,10 and the main raw
material for this serotonergic genesis, which is the essential amino
acid L-tryptophan, together with vitamin D, regulating the synthesis
of serotonin and degradation.11
In this sense, foods containing L-tryptophan are of fundamental
importance in serotonergic neurotransmission. However, the
participation of L-tryptophan still goes beyond neurotransmitter
genesis, because part of it is converted in the liver to niacin (vitamin
B3)12 with the help of enzymes that contain vitamin B6 and iron
and this niacin associated with pyruvate, omega 3, omega 6 and
oxygen are essential in the mitochondria to enable the Krebs cycle,
oxidative phosphorylation, formation of ATP, firing of neurons13 and,
consequently, it allows the production of Delta brain waves (2-4Hz),
Theta (4-7Hz), Alpha (8-12Hz), Beta-Low (12-15Hz), BETA (1523Hz), Beta-High (23-38Hz) and Gamma (38 -42Hz).14
In this context, one cannot fail to mention the minerals that are
essential for the realization of the entire biochemical process, such
as: phosphorus, which is important for pH regulation and for the
action of vitamin D3 and calcium and, above all, , which is essential
for the assimilation of niacin (also called nicotinamide or Vitamin
B3);15 sulphur, which makes up necessary amino acids for the
synthesis of essential metabolites and also makes up thiamine and
biotin; copper, which is a constituent of enzymes and substances in
the blood with an important role in the oxidation of iron before it is
transported in plasma; manganese, which is a constituent of essential
enzyme systems, abundant in mitochondria, responsible for cellular
respiration of liver cells, bone formation, cholesterol synthesis,
thiamine activation, glucose metabolism, synthesis and the release of
hormones from thyroid and prevention of allergic processes.16
Specifically, in neurotransmission, when L-tryptophan is
transported into the serotonergic neuron, it undergoes the action of
the enzyme tryptophan hydroxylase in the cytoplasm, transforming
into 5-hydroxytryptophane.17 Tryptophan (5-HTP) is decarboxylated
through unspecific action of the amino acid-decarboxylase enzyme
and, after the enzymatic action is converted to serotonin (5-HT).18
The process of degradation and inactivation of 5-HT is carried out
by a reuptake mechanism, where 5-HT passes through a membrane
transporter and after two reactions results in its main metabolite,
5-hydroxyindolacetic acid (5-HIAA).19
Currently, there are about seven types of serotonergic receptors
identified, they are: 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6
Copyright:
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168
and 5-HT7.20 Several receptor subtypes have also been described and
classified, such as 5-HT1A and 5-HT1B, among others.18
A wide variety of central nervous system functions have the
role of serotonin. It is also important to highlight the role of this
neurotransmission system in controlling aggressiveness,21 anxiety22
and depression.23 In depression, during the synapse, the 5-HT released
from the synaptic vesicle, detaching itself from the presynaptic neuron,
when in the cleft, it should go to a postsynaptic receptor, but it does
not, and returns to the same pre neuron -synaptic by transmembrane
protein, only this time, without the protection of the synaptic vesicle, it
is degraded by the enzyme monoaminaoxidase (MAO), transforming
into 5-hydroxyindole acetic acid (5-HIAA).24
Specifications of drug treatment approaches
Drug treatment can take place in three different approaches:
allopathy, homeopathy and phytotherapy or even by an informal,
uncontrolled and alternative method using medicinal plants without
control of standardized doses, called home remedies.
Allopathy
The law of similars is used in allopathy,25 In allopathy, the law of
similars is used, that is, medicines are used that, in the body, cause
effects contrary to the disease, seeking to eliminate the discomfort
generated by the symptoms.26 The production of the medication
comes from animal or vegetable origin and this drug can be called a
drug or medication, which can be a synthetic drug manufactured in
the laboratory.27
Allopathic drugs make it possible to increase serotonergic
availability in synaptic clefts in the case of depression.27 They can
act directly on the receptors, as agonists or antagonists, but they can
also play the role of reuptake inhibitors, blocking transmembrane
proteins.28
Allopathy is usually accepted by government oversight institutions
in most countries throughout the world, because they meet the
requirements of scientific evidence established by the natural sciences,
with high percentages of confidence interval, between 95% and 99%,
guaranteeing the minimum probability of error expressed in the level
of statistical significance, referenced, from the normal Gaussian
curve.28
Homeopathy
Homeopathy works with the law of opposites26 using substances
that slightly aggravate symptoms in order to make the body stronger
to fight it. The substance is derived from the three kingdoms: animal,
vegetable or mineral in the homeopathic approach.29
In the preparation of the substance, the first centesimal is used,
where a substance is diluted in 99 drops of water.29 If there is no
response from the organism, the second centesimal is prepared,
diluting that substance already diluted in another 99 drops of water
and so on, following the healing energy vis medicatrix naturae, letting
nature do its own work.30
However, the rule of not diluting 12 times is maintaine.26 The
professionals of this approach use the Avogadro number (as a
reference for the preparation of the substance), indicating the number
of atoms of Carbon-12, which together represent 12g of the substance
- 1 mol of C-12. The name of the constant is a tribute to the researcher
Amedeo Avogadro.31 Thus, it is not diluted 12 times, because in this
principle, if it is diluted 12 times, matter is lost.32
Citation: Ribas RMG, Oliveira DCL, Silva PC, et al. The different roles of Griffonia simplicifolia in the treatment of depression: a narrative review. Int J
Complement Alt Med. 2021;14(3):167‒171. DOI: 10.15406/ijcam.2021.14.00553
The different roles of Griffonia simplicifolia in the treatment of depression: a narrative review
Phytotherapy
Phytotherapy is equivalent to allopathy only in the use of the law
of similars. However, its substances come only from plant origin.33
Thus, unlike allopathic medicines, it cannot be called a drug, but
rather, an active ingredient.34 Even with these different singularities,
both allopathy and phytotherapy agree to increase the availability of
5-HT in the body and, mainly, in the synaptic cleft, in the treatment
of depression.35
In this sense, among these medicinal plants tested in the
laboratory, this study chose Griffonia simplicifolia, because, in
addition to presenting pharmacodynamic conditions for the treatment
of depression as a source of 5-hydroxytryptophan (5-HTP),36 the
Griffonia simplicifolia has the advantage of helping a larger number
of people, since its seed can contain up to 14% of 5-HTP, considering
that a capsule can contain up to 98% of 5-HTP.37
Method
It is a study with a qualitative, exploratory and descriptive
approach; source and bibliographic collection procedure. A narrative
review was carried out through a search in the electronic indexing
bases MEDLINE / PubMed, Web of Science, CAPES journals portal,
BIREME and Google Scholar.
Results
Griffonia simplicifolia
Griffonia is a plant from tropical Africa38 and belongs to the
Cercideae or Cercidoideae tribe, which is a subfamily of the pea
family, Fabaceae.39 There are 4 species of Griffonia. They are: 1)
Griffonia physocarpa, 2) Griffonia tessmannii and 3) Griffonia
speciosa, which are more common species in Nigeria, east of the
Democratic Republic of Congo and south for Angola, although
they are less common than 4) Griffonia simplicifolia.40 Griffonias
physocarpa, tessmannii and speciosa have similar medicinal uses,
such as treatment of gonorrhoea and stomach discomfort through
decoction. Griffonia physocarpa, speciosa and simplicifolia seeds
contain high concentrations of 5-HTP.40
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169
transport molecule. Absorption is also not influenced by amino acids,
which allows 5-HTP to be administered with meals, without losing
its effectiveness.47 The great advantage of 5-HTP extracted from
Griffonia simplicifolia is that it easily crosses the blood-brain barrier
- it does not require the presence of a transport molecule and it does
not compete with other amino acids to enter the brain.48 Therefore, it is
well absorbed after oral administration (70% of the dose is introduced
into the bloodstream).37
Another scientific evidence of great relevance was observed in a
study in the field of basic neuroscience with Griffonia simplicifolia
seed extract on the behavior of anxiety in rats in the open field test.49
In this test, animals tend to hide in the dark space, as a form of
protection from predators. Normally, animals do not spend much time
in the light area. When exposed to the open field of light, they tend to
manifest psychophysiological behaviors of fear and anxiety, such as:
urine, fecal cakes and tremors. In the dark light test, administration
of the extract at doses of 10 and 25mg/kg was able to significantly
increase the time spent in the light compartment.49
More very expressive evidence of 5-HTP in Griffonia simplicifolia
was observed in one study46 where Griffonia 5-HTP extract was
administered via spray in the oral cavity, and the adequacy of
absorption was confirmed by increasing the urinary 5-HIAA by 24h,
and that the supplementation of the diet of women with excess of
weight with 5-hydroxytryptophan increased the feeling of satiety
associated with a decrease in body mass index (BMI).46
It has also been shown that therapeutic administration of 5-HTP
can be effective in depression,50 fibromyalgia,51 chronic headaches
and insomnia.1 It also seems that Griffonia’s role goes beyond the
5-HTP offer, because, in Giurleo’s study, carried out in 2017,52 found
in Griffonia Simplicifolia, a great source of iron, zinc, copper and
magnesium.51 This study seems to allow another relevant reflection
regarding the role of Griffonia simplicifolia in the treatment of
depression, since iron and micronutrients (zinc and copper) allow
an increase in the availability of oxygen at the mitochondrial level,53
enabling the Krebs cycle, oxidative phosphorylation, ATP generation,
exothermic energy and quality neuron firing.13
Griffonia simplicifolia of the Fabaceae family of the
dicotyledonous class is a common shrub in western and central Africa,
especially in the Republic of Ghana, the Republic of Côte d’Ivoire and
the Togolese Republic.41,42
As for magnesium also found in Griffonia simplicifolia, it seems
relevant to emphasize its role as an activator of several enzymes,
participating in most organic processes, helping to control sodium
and potassium,54 and also acting in the neuromuscular process,55 in the
functioning of the immune56 and cardiovascular system.57
This plant can take the form of a climbing plant, especially when
it grows near tall trees. Griffonia can grow up to 3 meters.43 The
flowers produce black fruits with seeds that can be used as a source of
5-hydroxytryptophan (5-HTP).44
In this sense, cardiovascular performance seems to be enriched
with magnesium55 and, indirectly, it also contributes to the protection
of depressive processes,50 since it works, pumping blood in the
transport of oxygen to the mitochondria.13
Several researches have been showing that Griffonia simplicifolia
plant extracts increase the level of serotonin in the brain. Each seed is
estimated to contain about 6 to 14% 5-HTP37 in addition, the leaves of
plants contain serotonin in concentrations 0.1 to 0.2%.45
In some countries (United Kingdom, USA, Canada and Germany),
after an industrial extraction, researchers combine the contents of
several seeds to make available in each capsule 95-98% of 5-HTP
(TEIXEIRA et al., 2016), mixed with vitamins or with green tea or
even yerba mate.45
Another recent finding58 of phytochemical research seems to
corroborate this cardiovascular role in the process of optimizing brain
functioning, because, in Griffonia simplicifolia, it also revealed the
presence of secondary metabolites,50 such as alkaloids, triterpenoids,
flavonoids, steroids, saponins, glycosides, phenols, tannins and
coumarins, demonstrating that this cardiovascular functioning can
be further enhanced by the therapeutic properties in the treatment
of opportunistic bacterial infections and diseases associated with
oxidative stress58 increasing, thus, the availability of functional
oxygen to the cortical mitochondria.
In this form, Griffonia extracts are used as supplements to help
treat depression, reduce appetite and induce sleep. These products
commonly contain 50-100mg of 5-HTP.46 5-HTP, when ingested,
interacts with vitamin B6 and is converted to serotonin in the CNS.47
During the absorption of 5-HTP there is no need for a special
Even though it is known that Griffonia simplicifolia is a herbal
medicine, there is a need to be careful with the possibility of
interaction with other substances.50 A recent study59 with a 42-yearold male patient who developed hypomania after a week of using
Nutraceutical S-Adenosyl-L-Methionine (SAMe) associated with
Citation: Ribas RMG, Oliveira DCL, Silva PC, et al. The different roles of Griffonia simplicifolia in the treatment of depression: a narrative review. Int J
Complement Alt Med. 2021;14(3):167‒171. DOI: 10.15406/ijcam.2021.14.00553
The different roles of Griffonia simplicifolia in the treatment of depression: a narrative review
Copyright:
©2021 Ribas et al.
170
5-hydroxytryptophan (5-HTP) for the treatment of depression,
it demonstrated that this combination can induce hypomanic
episodes.59.60 S-Adenosyl-L-Methionine is a substance that has been
used as a supplement to stimulate mood and help decrease joint
stiffness and liver function.61
5. Grosso AF. Cannabis: de planta condenada pelo preconceito a uma das
grandes opções terapêuticas do século. Journal of Human Growth and
Development. 2020;30(1):94–97.
Another very significant aspect of Griffonia simplicifolia in the
treatment of depression may be the improvement in sleep quality.
5-HTP undergoes a decarboxylation process through the enzyme
5-HTP decarboxylase, giving rise to serotonin.62 In one of its metabolic
routes, serotonin is acetylated by the enzyme AA-NAT, giving rise to
N-Acetylserotonin (NAS) which, in turn, is methylated by HIOMT to
form melatonin.63
7. Branco DMD, Costa T. Relationship between the action of 5–
hydroxytriptophan and the effect on saciety and mood in overweight and
obesity women after oral administration of gryffhonia simplicifolia extract
capsules. Revista InterCiência–IMES Catanduva. 2019;1(2):53–53.
The last contribution of this narrative review on the important
roles of Griffonia simplicifolia in the treatment of depression would
be its indication for controlling anxiety indirectly.64,65 According to
Neurologist Sigmund Freud, while infectious diseases are caused
by pathogens, mental illnesses have their aetiologies in uncontrolled
anxiety. Although Freud brought this information in the context of
ego defences, as ways of thinking that minimize symptoms of anxiety
(mechanisms of psychic defences), it cannot be denied, that several
physical phenomena also participate in the control of anxiety, among
them: breathing, the adrenal gland, respiratory microcirculation and
neurotransmitters.50
9. Brito JS, Borges NA, Dolenga CJR, et al. Is there a relationship between
tryptophan dietary intake and plasma levels of indoxyl sulfate in chronic
kidney disease patients on hemodialysis? / Is there a relationship between
dietary intake of tryptophan and plasma levels of indoxyl sulfate in
chronic renal patients undergoing hemodialysis? Brazilian Journal of
Nephrology. 2016;38(4):396–402.
11. Patrick RP, Ames BN. Vitamin D hormone regulates serotonin synthesis.
Part 1: relevance for autism. FASEB J. 2014;28(6):2398–2413.
Conclusion
12. DE Maria CAB, Moreira RFA. A intrigante bioquímica da niacina–uma
revisão crítica. Quim Nova. 2011;34(10):1739–1752.
This narrative review found several studies, demonstrating that
Griffonia simplicifolia plant extracts increase the level of serotonin in
the brain. The studies presented in this narrative review demonstrate
that each Griffonia simplicifolia seed can contain up to 14% 5-HTP.
It was also observed in this review article that countries in the United
Kingdom, United States of America, Canada and Germany gather the
contents of several seeds to make 95-98% 5-HTP available in each
capsule.
The great advantage of 5-HTP extracted from Griffonia
simplicifolia is that it easily crosses the blood-brain barrier and 70%
of the dose is absorbed into the bloodstream after oral administration.
It was also shown that the therapeutic use of 5-HTP can be efficient
in the treatment of fibromyalgia, chronic headaches, insomnia, in
controlling anxiety and, above all, in depression.
Acknowledgments
None.
Conflicts of interest
Author declares there are no conflicts of interest.
Funding
None.
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Citation: Ribas RMG, Oliveira DCL, Silva PC, et al. The different roles of Griffonia simplicifolia in the treatment of depression: a narrative review. Int J
Complement Alt Med. 2021;14(3):167‒171. DOI: 10.15406/ijcam.2021.14.00553