Traditional Medicinal Uses, Phytoconstituents, Bioactivities, and Toxicities of Erythrina abyssinica Lam. ex DC. (Fabaceae): A Systematic Review

Samuel Baker Obakiro; Ambrose Kiprop; Elizabeth Kigondu; Isaac K’Owino; Mark Peter Odero; Scolastica Manyim; Timothy Omara; Jane Namukobe; Richard Oriko Owor; Yahaya Gavamukulya; Lydia Bunalema

Background. Many studies have been undertaken on the medicinal values of Erythrina abyssinica Lam. ex DC. (Fabaceae). The details, however, are highly fragmented in different journals, libraries, and other publication media. This study was therefore conducted to provide a comprehensive report on its ethnobotany, ethnomedicinal uses, phytochemicals, and the available pharmacological evidence supporting its efficacy and safety in traditional medicine. Method. We collected data using a PROSPERO registered systematic review protocol on the ethnobotany, phytochemistry, and ethnopharmacology of Erythrina abyssinica from 132 reports that were retrieved from electronic databases. Documented local names, morphology, growth habit and habitat, ethnomedicinal and nonmedicinal uses, diseases treated, parts used, method of preparation and administration, extraction and chemical identity of isolated compounds, and efficacy and toxicity of extracts and isolated compounds were captured. Numerical da...

Hindawi Evidence-Based Complementary and Alternative Medicine Volume 2021, Article ID 5513484, 43 pages https://doi.org/10.1155/2021/5513484 Review Article Traditional Medicinal Uses, Phytoconstituents, Bioactivities, and Toxicities of Erythrina abyssinica Lam. ex DC. (Fabaceae): A Systematic Review Samuel Baker Obakiro ,1,2,3 Ambrose Kiprop ,2,3 Elizabeth Kigondu,4 Isaac K’Owino,5,3 Mark Peter Odero ,2,3 Scolastica Manyim ,2,3 Timothy Omara ,2,3,6 Jane Namukobe,7 Richard Oriko Owor ,8 Yahaya Gavamukulya ,9 and Lydia Bunalema10 1 Department of Pharmacology and Therapeutics, Faculty of Health Sciences, Busitema University, P.O. Box 1460, Mbale, Uganda Department of Chemistry and Biochemistry, School of Sciences and Aerospace Studies, Moi University, P.O. Box 3900-30100, Eldoret, Kenya 4 Centre of Traditional Medicine and Drug Research, Kenya Medical Research Institute, P.O. Box 54840-00200, Nairobi, Kenya 10 Department of Pharmacology and Therapeutics, School of Biomedical Sciences, Makerere University College of Health Sciences, P.O. Box 7062, Kampala, Uganda 5 Department of Pure and Applied Chemistry, Faculty of Science, Masinde-Muliro University, P.O. Box 190-50100, Kakamega, Kenya 3 Africa Centre of Excellence II in Phytochemicals, Textiles and Renewable Energy (ACE II PTRE), Moi University, P.O. Box 3900-30100, Eldoret, Kenya 9 Department of Biochemistry and Molecular Biology, Faculty of Health Sciences, Busitema University, P.O. Box 1460, Mbale, Uganda 7 Department of Chemistry, School of Physical Sciences, College of Natural Sciences, Makerere University, P.O. Box 7062, Kampala, Uganda 6 Department of Quality Control and Quality Assurance, Product Development Directory, AgroWays Uganda Limited, Plot 34-60, Kyabazinga Way, P.O. Box 1924, Jinja, Uganda 8 Department of Chemistry, Faculty of Science Education, Busitema University, P.O. Box 236, Tororo, Uganda 2 Correspondence should be addressed to Samuel Baker Obakiro; sobakiro@gmail.com Received 12 January 2021; Revised 16 February 2021; Accepted 22 February 2021; Published 4 March 2021 Academic Editor: Riaz Ullah Copyright © 2021 Samuel Baker Obakiro et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Many studies have been undertaken on the medicinal values of Erythrina abyssinica Lam. ex DC. (Fabaceae). The details, however, are highly fragmented in diﬀerent journals, libraries, and other publication media. This study was therefore conducted to provide a comprehensive report on its ethnobotany, ethnomedicinal uses, phytochemicals, and the available pharmacological evidence supporting its eﬃcacy and safety in traditional medicine. Method. We collected data using a PROSPERO registered systematic review protocol on the ethnobotany, phytochemistry, and ethnopharmacology of Erythrina abyssinica from 132 reports that were retrieved from electronic databases. Documented local names, morphology, growth habit and habitat, ethnomedicinal and nonmedicinal uses, diseases treated, parts used, method of preparation and administration, extraction and chemical identity of isolated compounds, and eﬃcacy and toxicity of extracts and isolated compounds were captured. Numerical data were summarized into means, percentages, and frequencies and presented as graphs and tables. Results. Erythrina abyssinica is harvested by traditional herbal medicine practitioners in East, Central, and South African communities to prepare herbal remedies for various human and livestock ailments. These include bacterial and fungal infections, tuberculosis, malaria, HIV/AIDS, diarrhea, cancer, meningitis, inﬂammatory diseases, urinary tract infections, wounds, diabetes mellitus, and skin and soft tissue injuries. Diﬀerent extracts and phytochemicals from parts of E. abyssinica have been scientiﬁcally proven to possess anti-inﬂammatory, antibacterial, antioxidant, antiplasmodial, antiproliferative, antifungal, antimycobacterial, antidiarrheal, anti-HIV 1, antidiabetic, and antiobesity activities. This versatile pharmacological activity is due to the abundant ﬂavonoids, 2 Evidence-Based Complementary and Alternative Medicine alkaloids, and terpenoids present in its diﬀerent parts. Conclusion. Erythrina abyssinica is an important ethnomedicinal plant in Africa harboring useful pharmacologically active phytochemicals against various diseases with signiﬁcant eﬃcacies and minimal toxicity to mammalian cells. Therefore, this plant should be conserved and its potential to provide novel molecules against diseases be explored further. Clinical trials that evaluate the eﬃcacy and safety of extracts and isolated compounds from E. abyssinica are recommended. 1. Introduction Erythrina abyssinica Lam. ex DC. (Fabaceae) is an important medicinal plant as evidenced by the existence of its names in various local languages and high frequency of citation in ethnobotanical surveys [1–4]. The genus Erythrina derives from the Greek word “erythros,” translated to mean red (a reﬂection of the showy red ﬂowers of its various species). The epithet ‘‘abyssinica’’ means ‘‘from Ethiopia’’ [5]. The Erythrina genus houses at least 120 species distributed mainly in tropical and subtropical zones [6]. Plants in this genus are usually referred to as “coral trees” due to their red ﬂowers and branches that resemble the shape of sea coral [7]. Erythrina abyssinica is a deciduous leguminous tree native to East Africa but also found in Central and South Africa [8, 9]. Tropical Asia and Central America have E. abyssinica as an exotic species. The common English names of E. abyssinica are coral tree, Uganda coral, kaﬃr boom, erythrina, ﬂame tree, red-hot-poker tree, and lucky-bean tree [10]. Some of the local names used across indigenous communities are summarized in Table 1. Medicinal plants have been a veritable source of cure for a number of human and livestock diseases, and thus, they are widely used in many communities. This is because plants house abundant secondary metabolites (phytochemicals) with potential pharmacological activities. These include ﬂavonoids, alkaloids, terpenoids, phenols, chalcones, quinones, aromatic hydrocarbons, chromones, and coumarins. It is these phytochemicals that are locally extracted in herbal preparations and used as remedies for the management of several diseases. The World Health Organization (WHO) estimated that 80% of the world’s population especially in low- and middle-income countries rely on herbal medicines for primary health care [30]. The use of herbal medicines in the management of several ailments among people continues to gain momentum due to their availability, aﬀordability, perceived eﬀectiveness, and cultural acceptability across ethnic backgrounds [31]. Globally, there has been an increase in natural product research in the last two decades [30, 32]. This has been partly in response to the increasing antimicrobial resistance, emergence of new diseases, and decrease in the chemical diversity of natural product libraries [30, 32–36]. It has also been so in an eﬀort to continue the search for more eﬀective, safer, and cheaper therapeutic agents for existing diseases, to substitute expensive prescription drugs [37–40]. Erythrina abyssinica is among those revered plants [40, 41] that has been widely researched [3]. However, the information on it is highly fragmented in diﬀerent journals, books, university libraries, and other publication media platforms. This review was therefore undertaken to compile a comprehensive document that describes the ethnobotany, phytochemistry, and ethnopharmacology of E. abyssinica so as to generate integrated and suﬃcient scientiﬁc evidence to support its medicinal use. The study further emphasizes the importance of conserving this medicinal plant amidst the growing destruction of natural resources for settlement, industrialization, construction, and energy production [27, 42–47]. 2. Methods 2.1. Protocol Registration and Reporting. The protocol used in this systematic review was registered with the International Prospective Register of Systematic Reviews (PROSPERO) and can be accessed from their website (https://www. crd.york.ac.uk/prospero/display_record.php? ID�CRD42020187081) with the registration number CRD42020187081. The Preferred Reporting Items for the Systematic Reviews and Meta-Analyses (PRISMA) guidelines [48] have been used in the reporting of this study (Figure 1). 2.2. Literature Search. Electronic data on ethnobotany, phytochemistry, eﬃcacy, and toxicity of E. abyssinica were retrieved from electronic databases such as Scopus, Web of Science Core Collection, PubMed, American Chemical Society, ScienceDirect, Scientiﬁc Electronic Library Online (SciELO), Google Scholar, and NAPRALERT (a comprehensive natural products database with ethnomedical and pharmacological information of extracts and isolated compounds). Sets of keywords such as “ethnobotany,” “traditional medicine,” “ethnobotany,” “alternative medicine,” “ethnopharmacology,” “phytochemistry,” “extraction,” “isolation,” “eﬃcacy,” “safety,” “toxicity,” “phytochemicals,” “structural elucidation,” and clinical study were combined with “Erythrina abyssinica.” The retrieved articles were downloaded and stored in EndNote X9 (Thomson Reuters, San Francisco, CA, USA) by three independent authors (SBO, TO, and YG). Duplicate articles were then removed from the ﬁle. Further, manual search from the reference lists of screened eligible articles and deposited electronic copies of dissertations and theses in University online libraries were done. The authors continuously received notiﬁcations of any new “similar reports” meeting the search criteria from ScienceDirect, Scopus, and Google Scholar. 2.3. Screening. Retrieved articles were ﬁrst screened based on the titles and abstracts for relevance to the study by three independent reviewers (MPO, SM, and YG). Articles that reported on other species of Erythrina but not abyssinica and Evidence-Based Complementary and Alternative Medicine 3 Table 1: Local names of Erythrina abyssinica used across African communities. Eligibility Screening Identiﬁcation Folk name (local language) Country Authors Ejjirikiti (Luganda), Murinzi, Kiko Omoko/Echuko (Rutoro, Rukonzo), Oluo (Lugbara), Kisoro, Lochoro, Oding, Loting (Acholi), Kikiri (Kwamba), Engosorot (Ateso), Olawu Uganda [2, 3, 10–15] (Madi), Koli (Jopadhola), Owila kot (Lango), Muyirikiti, Ekilama (Lusoga), Cheroguru, Muragolo (Lugishu), Mutembetembe (Lugwe), Bwiko (Lukiga), Kaborte (Sebei), Kiko, Muko (Lunyangkore, Lutoro), Mudongodongo, Mukobe (Lunyuli) Omotembe (Kisii), Muhuti (Kikuyu), Ekirikiti or Ol-Goroshe (Maasai), Muuti (Meru), Kivuti or Muvuti (Kamba), Mulungu (Taita), Mwamba ngoma, Mbamba ngoma, Muhuti, Kenya [10, 16–19] Mjafari or Mwamba (Kiswahili), Kumurembei (Luhya) Qanqari (Iraqw), Mriri (Chagga), Muhemi (Hehe), and Muungu (Pare), Kisebhe (Rungwe) Tanzania [20–22] Kuara, Korra, Korch (Amharic) Ethiopia [10] Umuko (Lunyarwanda) Rwanda [23–26] Dus (Arabic), Hab al Arous Sudan, South Sudan [10, 27, 28] Chisunga (Lunda) Democratic Republic of Congo [10] Mulunku (Chokwe) Angola [4] Mozambique, Zimbabwe, [10] Mulunguti, Mwale (Nyanja) Zambia, Malawi Zambia, Mozambique, [5, 10] Mulunguti (Bemba, Tongan) Zimbabwe Mutiti (Shona) Zimbabwe [5] Suwawue, Soaueh (Tigrigna) Eritrea, Ethiopia [10, 29] Records identiﬁed through scopus, web of science, PubMed, scienceDirect, American chemical society (SciFinder scholar), NAPRALERT, SciELO, and Google scholar (n = 819) Additional records identiﬁed through other sources such as University electronic libraries (n = 13) Duplicates removed (n = 30) Records after duplicates removed (n = 802) Records excluded based on titles and abstracts (n = 601) Full-text articles assessed for eligibility (n = 201) Full-text articles excluded, with reasons (n = 39) articles not in English or French (n = 8) review articles (n = 11) did not rovide an data (n = 22) Included Full articles assessed for eligibility (n = 121) Full-text articles retrieved from reference list check through manual search (n = 11) Studies included in the review (n = 132) Figure 1: PRISMA ﬂow diagram showing the search and retrieval steps of the study (adopted from Moher et al. [48]). 4 also abyssinica but not of genus Erythrina were also excluded. For example, we excluded articles on Entada abyssinica, Erythrina variageta, Erythrina suberosa, Albuca abyssinica, Dregea abyssinica, Harrisonia abyssinica, and Wahlenbergia abyssinica although they appeared in the search results. During the screening, every time a disagreement occurred it was resolved through a discussion between the reviewers and/or by the principal investigator (SBO). The eligible articles were then assessed further for inclusion in the study using the inclusion/exclusion criteria. 2.4. Inclusion and Exclusion Criteria. Full-text articles that at least reported on ethnobotany, ethnopharmacology, and phytochemistry of Erythrina abyssinica written in English or French but translated to English and published in peerreviewed journals, reports, books, theses, and dissertations dated until January 2021 were considered. All publishing years were included without any geographical restrictions. Articles that reported data not relevant to the study, reviews, and not written in English or French were excluded from the study. 2.5. Data Extraction. A data collection tool was designed in Microsoft Excel (Microsoft Corporation, USA) to capture data on diﬀerent aspects of E. abyssinica. Three reviewers independently extracted relevant data from the included articles regarding the ethnobotany, ethnopharmacology, and phytochemistry of E. abyssinica. For ethnobotanical data, the diseases or ailments managed, parts used, and mode of preparation and administration were captured. For phytochemistry, the name of isolated pure compounds, chemical class, extraction solvent, and their eﬃcacy and toxicity were captured. For ethnopharmacology, extraction solvent used, bioassay/model used, results of eﬃcacy, and toxicity of extracts were captured. The collected data were checked for completeness and processed independently by two reviewers. 2.6. Data Analysis and Synthesis. Descriptive statistical methods were used to analyse the collected data. Results were expressed as percentages and frequencies and subsequently presented as tables and charts. The analyses were performed using SPSS statistical software (version 20, IBM Inc.). 3. Results and Discussion 3.1. Literature Search and Publications. A total of 201 reports were retrieved out of which 132 met the inclusion criteria and were reviewed. Of these, 78 articles reported only on the ethnobotany, 27 articles on pharmacology only, 15 articles on both pharmacology and phytochemistry, 5 articles on phytochemistry only, and 3 articles on both ethnobotany and pharmacology while 4 articles on ethnobotany, pharmacology, and phytochemistry. Most of the articles (56.8%) were published in the 2010–2019 decade, indicating a lot of research is being done as compared to the preceding decades Evidence-Based Complementary and Alternative Medicine (Figure 2). This could be due to the (1) growing need for more eﬀective and less toxic medicinal products of plant origin, (2) emerging antimicrobial resistance that has rendered most chemotherapeutic agents less eﬀective, (3) new disease outbreaks like Ebola, and (4) increase in noncommunicable diseases such as cancers, hypertension, diabetes mellitus, and sexual dysfunction that require readily available, aﬀordable, eﬀective, and safe therapies. 3.2. Taxonomy, Morphology, Distribution, and Propagation. Erythrina abyssinica belongs to the kingdom Plantae, phylum Spermatophyta, subphylum Magnoliophyta (ﬂowering plants), class Magnoliopsida (dicotyledons), order Fabales, family Fabaceae (legumes), subfamily Papilionoideae, genus Erythrina (L.), and species abyssinica (Lam ex. DC.). The frequently encountered synonyms of this species include E. kassneri Baker f., Corallodendron suberifera (Welw. ex Baker) Kuntze, E. bequaerti De Wild., E. tomentosa R. Br., Chirocalyx abyssinicus (Lam.) Hochst., and C. tomentosus Hochst. [3]. Erythrina abyssinica grows as a multibranched deciduous tree or shrub up to a height of 12–15 m tall usually with a rounded spreading crown (Figure 3). The branches have a corky thick deeply ﬁssured bark with prickles (4–8 mm long). The leaves are trifoliate alternately arranged with long (6–20 cm) petiole. The leaﬂets can be ovate, cordate, and almost circular, rounded at the base and obtuse or notched at the apex, with network venation, dense hair usually at the abaxial surface, and prickles [49, 50]. The inﬂorescence is raceme, dense, pyramidal, and either terminal or axial with a long peduncle (up to 20 cm) and caducous bracts. Flowers are bisexual and papilionaceous having densely hairy, cylindrical, split at one side calyx, brightly coloured (orange to red) corolla with free keel petals, 10 fused and one free stamen, one carpel with a superior cylindrical oblong ovary, long style, and ﬂat stigma head [51]. The fruits are linearoblong pods, brown to black in colour, usually hairy, dehisce at two values to release ellipsoid, long (6–12 mm), and bright red seeds [52]. The tree is anchored ﬁrmly in the ground by a deep root system [13, 20]. Erythrina abyssinica can be propagated either using seeds, wildings [40], or cuttings, but the former has comparatively lower germination rates of 10–30% with propagation restricted to rainy seasons [3, 11, 53]. It grows naturally in woodland and wooded grasslands (savannah woodlands, grasslands, and scrublands, secondary scrub vegetation, regions with 500–2000 mm annual rainfall and optimal temperatures of 15–25°C) [11, 54–57]. Thus, it is widespread from Sudan, South Sudan, Uganda, Kenya, Rwanda, Burundi, Democratic Republic of Congo, Congo (Brazzaville), Tanzania to Ethiopia, Eritrea, Angola, Namibia, Botswana, Central African Republic, Swaziland, Lesotho, Gabon, Zambia, Zimbabwe, and Mozambique (Figure 4) [3, 10, 11, 53]. It has also been introduced as an ornamental in Mauritius and various places in Tropical Asia and Central America, including Afghanistan, Bangladesh, Bhutan, India, Nepal, Pakistan, and Sri Lanka [10, 53]. In South Sudan for instance, the tree grows at up to 2000 m Evidence-Based Complementary and Alternative Medicine 5 6 2020 – present 75 2010 – 2019 26 2000 – 2009 12 1990 – 1999 9 1980 – 1989 4 Before 1980 0 20 40 60 80 Figure 2: Number of reports on ethnomedicinal and nonmedicinal traditional uses, phytochemistry, pharmacology, and toxicity of E. abyssinica published up to date. (a) (b) Figure 3: Erythrina abyssinica: (a) tree growing in its natural habitat and (b) leaves (photos taken by Samuel Baker Obakiro from Katakwi District, Eastern Uganda). altitude while in Tanzania, they are found at up to 2300 m. The tree naturally grows on loamy to clay soils, with preference for deep well-drained soils on plateaus and slopes with a pH of 3.5–5.5. The tree is termite- and ﬁre-resistant primarily due to its deep root system but cannot tolerate frost, explaining its limited distribution in cold regions [11, 53]. 3.3. Ecological, Traditional, and Medicinal Uses. Erythrina abyssinica being a legume is well known for ﬁxing nitrogen into the soil and thus enhances soil fertility. Because of this, it plays an important role in phytorestoration and forest regeneration in polluted soils [64–66]. Its ﬂowers also secrete nectar that is fed on by pollinating insects especially bees hence being important in both horticulture and apiculture [67]. Although this plant usually grows naturally in the wild, some communities cultivate it in their homesteads as an ornamental plant, for live fencing purposes due to its brightly coloured ﬂowers and prickles, a material for dye, and craft materials such as curios and necklaces (from seeds) [9, 20, 68, 69]. The stem of this plant is also harvested to obtain timber and charcoal for furniture and energy purposes, respectively [20]. In livestock farming, the plant leaves are used as fodder for animals [5, 70, 71]. The stem bark, seeds, roots, root bark, leaves, and ﬂowers of E. abyssinica and the whole plant either in combination or 6 Evidence-Based Complementary and Alternative Medicine Figure 4: Native geographical distribution of E. abyssinica (based on retrieved literature [4, 10, 11, 15, 21, 23–25, 27–29, 58–63]). singly are used to prepare herbal remedies for various human ailments (Table 2). However, the stem bark and roots are the most commonly used parts in the preparation of herbal remedies. Even in eﬃcacy, toxicity, and phytochemical studies, the stem bark and roots were the most investigated. This could probably be due to high yield associated with them because of their high potential in concentrating and storing phytochemicals. The seeds were indicated to be poisonous when crushed [11]. The commonest methods of preparation and administration of herbal medicines from this plant are boiling (decoctions) and then drinking, cold infusions (taken orally), pounding dried samples into powder and then licking, pounding fresh samples into a paste and applying topically, squeezing fresh samples and mixing with bathing water, or direct chewing of the diﬀerent parts (Table 2). Among the frequently reported ailments for which herbal medicines containing E. abyssinica are used include bacterial and fungal infections, malaria, leprosy, tuberculosis (cough), inﬂammatory diseases, HIV/AIDS, cancer, and metabolic disorders such as diabetes mellitus, obesity, and anaemia. Other conditions treated using this plant include snake bites, antagonizing poisons, venereal diseases (sexually transmitted diseases, e.g., gonorrhea, syphilis, and urinary tract infections including schistosomiasis), soft tissue and skin infections, diarrhea, infertility and pregnancy-related conditions, pneumonia, epilepsy, central nervous system- (CNS-) related disorders, vomiting, hepatitis, and helminthiasis. In ethnoveterinary medicine, extracts of E. abyssinica are used in the management of poultry and livestock diseases such as new castle disease, anaplasmosis, and helminthosis [43, 89, 119, 123, 124]. 3.4. Phytochemical Proﬁle of E. abyssinica 3.4.1. Preliminary Phytochemical Analyses. Qualitative phytochemical screening of medicinal plants is an essential step to their detailed phytochemical and pharmacological investigation [125]. Preliminary phytochemical screening of diﬀerent solvent extracts of E. abyssinica indicated the presence of tannins, saponins, alkaloids, and ﬂavonoids as the main therapeutic secondary metabolites (Table 3). 3.4.2. Structural Elucidation. Like in many natural product research studies, chromatography has been used in the isolation of compounds from crude extracts of E. abyssinica. The most widely used techniques included high-performance liquid chromatography (HPLC), gas chromatography (GC), high-performance thin-layer chromatography (HPTLC), and ultraperformance liquid chromatography (UPLC) [129]. Spectroscopic techniques such as mass spectrometry (MS), ultraviolet (UV) spectrophotometry, one-dimensional nuclear magnetic resonance (1D-NMR) spectroscopy, and its complementary techniques (heteronuclear multiple bond correlation (HMBC) spectroscopy, heteronuclear multiple quantum coherence (HMQC) spectroscopy, nuclear overhauser eﬀect spectroscopy (NOESY), and circular dichroism (CD) spectroscopy) have been used to elucidate chemical structures of the isolated compounds [130]. Chromatography-spectroscopy hyphenated techniques have become more commonly used in recent decades due to the increased eﬃciency, sensitivity, and detection limits [1]. These include LC-MS, GC-MS, UPLCMS, HPTLC-UV, HPLC-photodiode array detection, LC- Evidence-Based Complementary and Alternative Medicine 7 Table 2: Ethnobotanical uses of Erythrina abyssinica reported in the literature. No. 1 Disease/ailments treated Parts used Malaria, fevers R, SB, L, F 2 Inﬂammatory disorders, eye problems, and pain SB, R, Sd 3 Bacterial and fungal infections SB, L, F, WP 4 Skin and soft tissue infections, leprosy, and wounds SB, F, L 5 Tuberculosis (cough) SB, R, L, F 6 Cancer 7 HIV/AIDS 8 9 SB, L, F SB, R, L Infertility, birth control, pregnancy related SB, R conditions Blood disorders (anaemia R, SB, and jaundice) L, F 10 Venereal diseases SB, L, F, RB 11 Diabetes mellitus SB, L 12 13 14 15 16 17 Method of preparation and administration Country Authors Boiled and taken orally Uganda, Kenya, Tanzania, Ethiopia, Eritrea, DR Congo, Sudan, Rwanda [9, 13, 18, 21, 24, 28, 58, 72–82] Boiled and taken orally; powdered, mixed with Uganda, Tanzania, petroleum jelly, and smeared Kenya, South on the wound/swollen part. Sudan For eye problems, it is applied as liniment Decoction taken orally; Uganda, Kenya, powdered and licked; sliced Burundi bark chewed; cold infusion taken orally Boiled in petroleum jelly and Uganda, Kenya, Zimbabwe, smeared at the tissue, herbal Rwanda bath of infected skin part Uganda, Kenya, Decoction taken orally; Tanzania, Burundi, powdered and licked Zimbabwe [13, 19, 20, 27, 72, 83–88] [13, 72, 89–91] [20, 24, 72, 81, 87, 92–95] [31, 61, 72, 73, 95–99] Boiled and taken orally Uganda, Kenya [39, 72, 100] Decoction taken orally Uganda, Kenya, Tanzania [2, 39, 72, 98, 101–103] Decoction, squeezing, chewing, taken orally Uganda, Kenya [31, 72, 73, 104–106] Boiled and taken orally Boiled and taken orally Uganda, Kenya, Tanzania Uganda, Kenya, Zimbabwe, Rwanda Uganda Boiled and taken orally Decoction and cold infusions Hepatitis, measles, scabies, SB, R, taken. Dried leaf ash is mixed Rwanda, Kenya, herpes, mumps, liver with oil or butter and applied Uganda, Tanzania L diseases externally to treat scabies Boiled in water and taken Kenya Pneumonia SB orally Decoction, pound, and add Convulsions and CNS Uganda SB salt disorders Boiled, honey added, and taken orally. Decoction taken, or pounded, salt added, and Gastrointestinal disorders Uganda, Kenya, (diarrhea, stomach ache, SB, R, taken. Root decoction with Tanzania, Eritrea, Rhamnus prinoides roots L vomiting, constipation, Angola, Rwanda taken for colic. Decoction of ulcers, dysentery, colic) young roots taken for constipation in children Uganda, Kenya, Helminthiasis SB Decoction taken orally Tanzania Sap used/pounded and Snake bites/antidote for R, SB, Uganda, Kenya, applied at the bite. Boiled and poisoning RB Tanzania taken orally Parts used: L: leaves, R: roots, RB: root bark, Sd: seeds, SB: stem bark, F: ﬂowers, and WP: whole plant. [27, 31, 72, 84, 107–109] [19, 20, 63, 72, 87, 92, 100, 105, 110–112] [72, 113, 114] [22, 23, 101, 115] [92, 100] [31] [4, 19, 26, 29, 31, 87, 92, 101, 106, 107, 116–118] [87, 105, 119, 120] [15, 16, 19, 109, 121, 122] 8 Evidence-Based Complementary and Alternative Medicine Table 3: Some secondary metabolites reported in E. abyssinica extracts. Secondary metabolites Tannins, saponins, alkaloids, and ﬂavonoids Alkaloids, terpenoids, saponins, tannins, and ﬂavones Alkaloids, saponins, cardiac glycosides, coumarins, and anthraquinone derivatives Parts used Bark Root bark Roots Solvent used Yield (%) Authors Hexane Methanol (crude) 2.0 [60] Not reported [126] Methanol 23.6 [127] [128] [62] Alkaloids, ﬂavonoids, tannins, and cardiac glycosides Stem Water 0.34 (alkaloidal and ﬂavonoid content) Alkaloids, ﬂavonoids, terpenoids, and saponins Stem bark Methanol 4.82 NMR-MS, GC-NMR-MS, and high-resolution electron spray ionization (ESI)-MS [130]. A total of 122 phytochemicals which are primarily alkaloids, ﬂavonoids, and triterpenoids have been isolated from E. abyssinica (Figure 5; Table 4). Some of the isolated compounds are speciﬁc to E. abyssinica while others have been reported to be present in other species of the genus Erythrina [149]. Because genus Erythrina belongs to the family Fabaceae, its members have a rich diversity of secondary metabolites (phytochemicals) amongst themselves due to possession of various biosynthetic pathways [150]. However, some species share common phytochemicals, and hence, these act as biomarkers for nutraceutical, pharmacological, and toxicological potentials in the food and drug industries [130, 151]. (1) Alkaloids. In the present study, we retrieved thirteen alkaloids (1–12 and 95) that have been isolated from E. abyssinica (Table 4, Figure 5). The Erythrina alkaloids have a tetracyclic carbon skeleton with three rings (A, B, and C) common to all the alkaloids and the fourth ring (D) which varies among the diﬀerent alkaloids [1, 152]. Lactonic alkaloids contain ring D as an unsaturated δ-lactone, dienoid alkaloids possess a benzenoid ring D (with two double bonds at C-1 and C-2, and C-6 and C-7), and alkenoid alkaloid possess a benzenoid ring D with a double bond between C-1 and C-6. Aromatic alkaloids and those containing a double bond at C-16 undergo stereoisomerism to give rise to other alkaloid derivatives [152]. (2) Flavonoids. A total of 106 ﬂavonoids have been isolated and identiﬁed from E. abyssinica. These include ﬁve benzofurans, six chalcones, two coumestans, six isoﬂavones and seventy-two ﬂavanones, four ﬂavones, and eleven pterocarpans. (i) Benzofurans. Benzofurans are heterocyclic compounds consisting of benzene and furan rings fused together. Five benzofurans (65–69) have been isolated from the stem bark of E. abyssinica [144]. (ii) Chalcones. Chalcones, also known as chalconoids or benzyl acetophenones, are α, β-unsaturated ketones made up of two aromatic rings (designated as rings A and B) with diverse substituents. They possess conjugated double bonds and a completely delocalized π-electron system on both benzene rings. Chalcones have been widely known in medicinal chemistry as potential templates for the synthesis of therapeutic agents [153]. In this study, seven chalcones (15, 28–32, and 47) were retrieved to have been isolated from the roots and stem bark of E. abyssinica. (iii) Coumestans. Coumestans are oxidized derivatives of pterocarpans consisting of a benzoxole fused to a chromen-2-one to form 1-benzoxolo[3,2-c]chromen-6-one. They are responsible for the phytoestrogenic activity of most medicinal plants of the family Fabaceae [154]. Two coumestans, erythribyssin N (62) and isosojagol (64), were isolated from the stem bark of E. abyssinica. (iv) Isoﬂavones and Flavanones. Isoﬂavones are a large group of ﬂavonoids possessing a 3-phenylchroman skeleton that is biosynthetically obtained by rearrangement of the 2-phenylchroman ﬂavonoid system. They are naturally occurring exclusively in the family Fabaceae (Leguminosae). Diﬀerences among isoﬂavones arise from the presence of extra heterocyclic rings, diﬀerent oxidation states in this skeleton, and the number of substituents on the isoﬂavone moiety [155]. On the other hand, ﬂavanones have the basic 2,3-dihydroﬂavone structure. They are distinguished from the rest of the ﬂavonoid class by the lack of a double bond between C-2 and C-3 and the presence of a chiral center at C-2 position. Members diﬀer from one another in the position and/or the number of the constituent methoxy and hydroxyl substituents [156]. Unlike isoﬂavones, ﬂavanones are naturally occurring in members of family Fabaceae, Compositae, and Rutaceae. A total of six isoﬂavones (25–27, 83, 110, and 111) and 72 ﬂavanones (14, 17–22, 24, 33–46, 48–61, 63, 70–75, 77–82, 84, 87–92, 100–103, 108, 109, 118–119, and 121–122) have been isolated from E. abyssinica root bark, stem bark, and roots. (v) Pterocarpans. Pterocarpans are structural analogs to isoﬂavonoids with a benzofurochromene skeleton. They can also be derived from coumestans through reduction reactions. They have two asymmetric centers at C-6a and C-11a and may exist as cis or Evidence-Based Complementary and Alternative Medicine 9 OCH3 H O H3CO N H N H3CO H H H H H3CO HO N HO H 5 N H H3CO 8 N H3CO H3CO HH 10 N O H H 9 H H3CO O H3CO H O H H N HO H H H3CO H3CO HO H N O 7 OCH3 O O H H H 6 H O H H3CO H3CO H3CO H H H H H3CO H N O H H 4 O H H H3CO 3 H H N H3CO H H 2 HO N HO H H HO 1 H N H3CO H H3CO O O O H3CO HO OH H H H H H H H H 11 12 O O H3CO O HO O OCH3 OH OH HO OH OH OCH3 14 13 15 OH HO O OH R1 R1 O O O O HO O HO OCH3 OH 16 OH O 17 R1 = H 18 R1 = OH (a) Figure 5: Continued. O 19 R1 = H, R2 = OCH3 20 R1 = H, R2 = OH 21 R1 = OH, R2 = OH R2 10 Evidence-Based Complementary and Alternative Medicine O R3 OH R4 R2 HO O O HO R1 O O O OH O O 23 R1 = R2 = H, R3 = OH, R4 = OCH3, R5 = prenyl 24 R1 = R4 = R5 = OH, R2 = R3 = Prenyl 22 O R5 OH 25 O O H3CO O O O O OH OH OH HO O 26 OH OH OH O 27 28 OH OH HO O HO OH OH OH O HO OH OH O HO O 29 OCH3 OH O 30 31 OH R3 O R1 HO O HO OH OH 32 O R2 O HO O OH O 33 R1 = prenyl, R2 = OH, R3 = CH3 34 R1 = H, R2 = OH, R3 = CH2OH 35 R1 = H, R2 = OCH3, R3 = CH2OH (b) O O 36 Evidence-Based Complementary and Alternative Medicine R5 R4 O O HO R3 R2 R1 11 O 37 R1 = R5 = OH, R2 = R4 = H, R3 = prenyl 38 R1 = R5 = OH, R2 = R4 = H, R3 = OCH3 39 R1 = R4 = R5 = OH, R2 = R3 = H 40 R1 = R4 = R5 = OH, R2 = H, R3 = prenyl 41 R1 = R4 = R5 = OH, R2 = prenyl, R3 = OH 42 R1 = R3 = OH, R2 = R5 = H, R4 = ( = 0) 43 R1 = R2 = R4 = H, R3 = R5 = OH 44 R1 = R2 = H, R3 = R4 = R5 = OH OCH3 O HO O OH O 45 OCH3 OCH3 OH O HO OH O OH O 48 HO OH O O O O O HO O OH OH HO O O OH O 50 49 HO O 47 OH OH O HO O 46 HO OH O HO 51 O OH O HO OCH3 HO O OH O HO OCH3 OH OH O OCH3 OH O OCH3 O 52 53 (c) Figure 5: Continued. 54 12 Evidence-Based Complementary and Alternative Medicine C5H9 O HO HO O C5H9 OH O O O HO O 55 O 56 57 C5H9 C5H9 OH OH O O C5H9 O HO O HO HO O O H3CO O 58 O C5H9 59 60 HO O O C5H9 OH HO C5H9 HO R 1O O O R2 OH R2 O 61 R3 62 R1 = H, R2 = COOH, R3 = prenyl 63 R1 = H, R2 = CHO, R3 = prenyl 64 R1 = CH3, R2 = CHO, R3 = H HO HO R1 HO O 65 R1 = H, R2 = CH3 66 R1 = Prenyl, R2 = H 67 R1 = R2 = = H OR2 R1 O OR2 OCH3 O R1 OCH3 R HO O R3 OH O OCH3 68 R = Alpha H 69 R = CHO 70 R1 = H, R2 = CH3 71 R1 = R2 = H 72 R1 = OH, R2 = H (d) Figure 5: Continued. 73 R1 = OCH3, R2 = H, R3 = prenyl 75 R1 = R2 = H,R3 = CHO 76 R1 = R2 = H, R3 = prenyl 77 R1 = R2 = R3 = H 78 R1 = R2 = H, R3 = OCH3 Evidence-Based Complementary and Alternative Medicine 13 OH O HO O OH O O O HO OH O HO O O O OH 74 79 76 OH O O HO OH O HO O O HO O O O OCH3 R O 81 R = prenyl 82 R = H 80 83 O HO R2 R1 O H O O(CH2)27-CH3 OH O OH OR3 HO OCH3 O HO 84 85 R1 = H, R2 = OH, R3 = CH3 86 R1 = CH2CH = C(CH3)2, R2 = H, R3 = H 87 OH OH OH O O OH O O HO O OH OH HO O HO 88 O 89 (e) Figure 5: Continued. 90 14 Evidence-Based Complementary and Alternative Medicine OH O OH O HO O O HO OH HO OH O 91 93 OCH3 OH OH HO HO N H3CO OH H H3CO O 94 95 96 OH = beta 115 OH = alpha OH O OH R3 OH O O HO OH O R2 O HO O 92 OH OH OH OH R1 OR2 HO HO O R1 97 R1 = H, R2 = Rha (1→2)Gal 98 R2 = H, R2 = Rha(1→2))Glc 99 R1 = OH, R2 = Rha(1→2)Gal 100 R1 = OH, R2 = Glc, R3 = Quin 101 R1 = OH, R2 = Quin, R3 = Glc 102 R1 = H,R2 = H, R3 = Rha(1→2)Glc 103 R1 = H, R2 = H, R3 = Xyl (1→2)Glc 104 R1 = OH, R2 = Glc, R3 = Ara 105 R1 = OH,R2 = Ara, R3 = Glc 106 R1 = OH, R2 = Glc, R3 = Glc OH OH HO HO HO OH O OH O O O OH HO HO O O H O O O OH O OH OH 107 108 (f ) Figure 5: Continued. 109 Evidence-Based Complementary and Alternative Medicine 15 O OH O OH OH O HO OH O O HO O O OH O OH O 110 O H OH O O O H O H O H H 112 111 OH OH 113 114 116 OH O HO O O O O HO O HO OH OH O OH O OH O 118 117 119 OH O O O O O OH O OH 120 121 OH HO OH O HO O OH O HO O O OH O O OH OH OH OH O OH 122 (g) Figure 5: Chemical structures of the phytochemicals isolated from E. abyssinica. The numbers: 1–122 correspond to compounds mentioned in Table 4. 16 Evidence-Based Complementary and Alternative Medicine Table 4: Phytochemical composition and pharmacological activities of compounds isolated from diﬀerent parts of Erythrina abyssinica. Name of the compound identiﬁed Chemical class Techniques Part Solvent used used used Bioactivity tested (+)-Erysotrine (1) Alkaloid NS NS NMR Not tested (+)-Erythravine (2) Alkaloid NS NS NMR Not tested (+)-Erythristemine (3) Alkaloid NS NS NMR Not tested (+)-Erysovine (4) Alkaloid NS NS NMR Not tested (+)-Erysodine (5) Alkaloid Sd (+)-Erysopine (6) Alkaloid Sd (+)-Erythraline (7) Alkaloid NS NS NMR Not tested (+)-8-Oxoerythraline (8) Alkaloid NS NS NMR Not tested (+)-11-Oxoerysodine (9) Alkaloid NS NS NMR Not tested (+)-11-Methoxyerysovine (10) Alkaloid NS NS NMR Not tested (+)-Erythratidine (11) Alkaloid NS NS NMR Not tested (+)-Erythratine (12) Alkaloid NS NS NMR Not tested 8-Methoxyneorautenol (13) Pterocarpan RB Eryvarin L (14) Benzofuran Rt Chalcone Tw Pterocarpan RB Licoagrochalcone A (15) 3-Hydroxy-9-methoxy10-(3,3-dimethylallyl) pterocarpene (16) (2S)-5,7-Dihydroxy-3′prenyl-2″ξ-(4″hydroxyisopropyl) dihydrofurano[1″,3″ : 4′,5′] ﬂavanone (17) (2S)-5,7-Dihydroxy-3′prenyl-2″ξ-(4″-hydroxyisopropyl)-3″-hydroxydihydrofurano[1″,3″: 4′,5′]ﬂavanone, and (2S)5,7,3′-trihydroxy-2′prenyl-2″ξ-(4″hydroxyisopropyl)-3″hydroxy-dihydrofurano [1″,3″: 4′,5′] ﬂavanone (18) (2S)-5,7-Dihydroxy-3′methoxy-2″ξ-(4″hydroxyisopropyl) dihydrofurano[1″,3″:4′, 5′]ﬂavanone (19) Flavanone Flavanone Flavanone SB SB SB Chloroform, ethanol Chloroform, ethanol NMR NMR Curare-like activity Curare-like activity Result Not applicable Not applicable Not applicable Not applicable Strong activity Strong activity Not applicable Not applicable Not applicable Not applicable Not applicable Not applicable Radical HRMS, Moderately scavenging NMR, active properties HMBC Good Chloroform: UV, NMR, Antimicrobial and antioxidant antioxidant EI-MS, methanol (1 : activity activities HMBC 1) Chloroform: UV, NMR, Antimicrobial Good radical and antioxidant scavenging EI-MS, methanol (1 : activity activities HMBC 1) Radical HRMS, scavenging Very active Acetone NMR, properties HMBC Acetone Authors [131] [131] [131] [131] [131, 132] [131, 132] [131] [131] [131] [131] [131] [131] [133] [134] [134] [133] Methanol UV, HPLC, NMR, HMQC, HMBC PTP 1B inhibitory activity No activity [135] Methanol UV, HPLC, NMR, HMQC, HMBC PTP 1B inhibitory activity No activity [135] Methanol UV, HPLC, NMR, HMQC, HMBC PTP 1B inhibitory activity No activity [135] Evidence-Based Complementary and Alternative Medicine 17 Table 4: Continued. Name of the compound identiﬁed (2S)-5,7,3′-Trihydroxy2″ξ-(4″hydroxyisopropyl) dihydrofurano[1″,3″ : 4′,5′] ﬂavanone (20) (2S)-5,7,3′-Trihydroxy2″ξ-(4″hydroxyisopropyl)-3″hydroxy-dihydrofurano [1″,3″:4′,5′] ﬂavanone (21) Erythrabyssin I (22) Chemical class Flavanone Flavanone Pterocarpan Techniques Part Solvent used used used Bioactivity tested Result Authors Methanol UV, HPLC, NMR, HMQC, HMBC PTP 1B inhibitory activity No activity [135] Methanol UV, HPLC, NMR, HMQC, HMBC PTP 1B inhibitory activity No activity [135] Methanol UV, NMR, HPLC Antimicrobial activity Moderate antiyeast and antifungal activities [136] No activity [135] Not applicable [82] Active [137] Not active [137] Not active [137] Not applicable [138] Not applicable [138] Not applicable [138] Not applicable [138] Good bioactivities [134] SB SB Rt UV, HPLC, PTP 1B NMR, inhibitory Methanol HMQC, activity HMBC HPLC, NMR, HREI-MS, Not tested Methanol HMQC, HMBC, NOESY FTIR, UV, DCM: Antimicrobial EI-MS, MeOH activity NMR FTIR, UV, Antimicrobial DCM: EI-MS, activity MeOH NMR FTIR, UV, DCM: Antimicrobial EI-MS, MeOH activity NMR UV, CD, NMR, Not tested Methanol HRMS UV, CD, Methanol NMR, Not tested HRMS UV, CD, Methanol NMR, Not tested HRMS UV, CD, Methanol NMR, Not tested HRMS Chloroform: UV, NMR, Antimicrobial and antioxidant EI-MS, methanol (1 : activities HMBC 1) Erylatissin C (23) Flavanone SB Abyssinin III (24) Flavanone SB Indicanine B (25) Coumarin RB Indicanine C (26) Isoﬂavone RB Cajanin (27) Isoﬂavone RB Abyssinone A (28) Chalcone SB Abyssinone B (29) Chalcone SB Abyssinone C (30) Chalcone SB Abyssinone D (31) Chalcone SB 3-Methylbutein (32) Chalcone Rt Flavanone SB Methanol UV, CD, NMR, HRMS PTP 1B inhibitory activity Good activity [138] Flavanone SB Methanol UV, CD, NMR, HRMS PTP 1B inhibitory activity No activity [138] 2(S)-5,5′,7-Trihydroxy-2′prenyl-(2″,2″dimethylpyrano)-(5″,6’’: 3′,4′)ﬂavanone (33) i2(S)-5,5′,7-Trihydroxy[2’’-(5″- hydroxy)methylpyrano]-(5″,6’’: 3′,4′)ﬂavanone (34) 18 Evidence-Based Complementary and Alternative Medicine Table 4: Continued. Techniques Part Name of the compound Solvent used Chemical class used used identiﬁed 2(S)-5,7-Dihydroxy-3′UV, CD, methoxy-[2’’-(5″Flavanone SB Methanol NMR, hydroxy)-methylpyrano]HRMS (5″,6’’:3′,4′)ﬂavanone (35) 2(S)-5,7-Dihydroxy[(5″,6’’:3′,4′)-(2″,2″UV, CD, dimethylpyrano)-(5‴,6‴: Flavanone SB Methanol NMR, 5′,6′)]-(2‴,2‴HRMS dimethylpyrano) ﬂavanone (36) 2(S)-5,7-Dihydroxy-5′UV, CD, prenyl-[2″,2’’-(3″Flavanone SB Methanol NMR, hydroxy)HRMS dimethylpyrano]-(5″,6’’: 3′,4′)ﬂavanone (37) 2(S)-5,7-Dihydroxy-5′UV, CD, methoxy-[2″,2’’-(3″Flavanone SB Methanol NMR, hydroxy)-dimethylHRMS pyrano]-(5″,6’’:3′,4′) ﬂavanone (38) 2(S)-5,7-DihydroxyUV, CD, [2″,2’’-(3″,4″-dihydroxy)Flavanone SB Methanol NMR, dimethylpyrano]-(5″,6’’: HRMS 3′,4′)ﬂavanone (39) 2(S)-5,7-Dihydroxy-5′UV, CD, prenyl-[2″,2’’-(3″,4″Flavanone SB Methanol NMR, dihydroxy)HRMS dimethylpyrano)]-(5″,6’’: 3′,4′)ﬂavanone (40) 2(S)-5,6′,7-Trihydroxy-5′UV, CD, prenyl-[2″,2’’-(3″,4″Flavanone SB Methanol NMR, dihydroxy)HRMS dimethylpyrano]-(5″,6’’: 3′,4′)ﬂavanone (41) 2(S)-5,5′,7-TrihydroxyUV, CD, [2″,2’’-(4″-chromanone)Flavanone SB Methanol NMR, dimethylpyrano]-(5″,6’’: HRMS 3′,4′)ﬂavanone (42) 2(S)-5′,7-DihydroxyUV, CD, [2″,2’’-(3″-hydroxy)Flavanone SB Methanol NMR, dimethylpyrano]-(5″,6’’: HRMS 3′,4′)ﬂavanone (43) 2(S)-5′,7-DihydroxyUV, CD, [2″,2’’-(3″,4″-dihydroxy)Flavanone SB Methanol NMR, dimethylpyrano]-(5″,6’’: HRMS 3′,4′)ﬂavanone (44) HPLC, NMR, HREI-MS, Abyssinin I (45) Flavanone SB Methanol HMQC, HMBC, NOESY HPLC, NMR, HREI-MS, Abyssinin II (46) Flavanone SB Methanol HMQC, HMBC, NOESY Bioactivity tested Result Authors PTP 1B inhibitory activity Good activity [138] PTP 1B inhibitory activity No activity [138] PTP 1B inhibitory activity Good activity [138] PTP 1B inhibitory activity Good activity [138] PTP 1B inhibitory activity No activity [138] PTP 1B inhibitory activity Good activity [138] PTP 1B inhibitory activity Good activity [138] PTP 1B inhibitory activity No activity [138] PTP 1B inhibitory activity No activity [138] PTP 1B inhibitory activity No activity [138] Not tested Not applicable [82] Not tested Not applicable [82] Evidence-Based Complementary and Alternative Medicine 19 Table 4: Continued. Name of the compound identiﬁed Chemical class Licochalcone A (47) Chalcone Abyssinone V 4′-methyl ether (48) Flavanone Abyssinoﬂavanone IV (49) Prenylated ﬂavanone Abyssinoﬂavanone V (50) Prenylated ﬂavanone Abyssinoﬂavanone VI (51) Prenylated ﬂavanone Sigmoidin D (52) Flavanone 5,7-Dihydroxy-2′,4′,5′trimethoxyisoﬂavanone (53) Isoﬂavanone 5-Prenylpratensein (54) Isoﬂavone Abyssinone I (55) Flavanone Abyssinone II (56) Flavanone Abyssinone III (57) Flavanone Abyssinone IV (58) Flavanone Techniques Bioactivity Part Result Solvent used used tested used Chloroform: UV, NMR, Antimicrobial and antioxidant Weak activity EI-MS, Rt methanol (1 : activities HMBC 1) UV, HPLC HREIMS, Not NMR, Not tested SB Methanol applicable HMQC, HMBC, NOESY UV, NMR, CD, HREINot MS, HPLC, Not tested SB Methanol applicable HMQC, HMBC, NOESY UV, NMR, CD, HREINot MS, HPLC, Not tested SB Methanol applicable HMQC, HMBC, NOESY UV, NMR, CD, HREINot MS, HPLC, Not tested SB Methanol applicable HMQC, HMBC, NOESY Weak Antimicrobial antimicrobial UV, NMR, and antioxidant Chloroform: and CD, EI-MS, Rt, activities, PTP methanol (1 : antioxidant HRMS, SB 1B inhibitory 1), methanol activities, no HMBC activity activity Chloroform: UV, NMR, Antimicrobial and antioxidant Weak activity EI-MS, Rt methanol (1 : activities HMBC 1) Chloroform: UV, NMR, Antimicrobial and antioxidant Weak activity EI-MS, Rt methanol (1 : activities HMBC 1) Antimicrobial Moderate 80% aqueous UV, HPLC RB activity activity MeOH, ether 80% aqueous Antimicrobial MeOH Moderate and and PTP1B RB UV, HPLC Ether no activity inhibitory Ethyl acetate activities PTP1B Ethyl acetate HPLC, IR, inhibitory and RB Weak activity UV, MS, antifungal Ether CD, NMR activities 80% aqueous MeOH UV, NMR, Antimicrobial Moderate RB Chloroform : HMBC, EI- and antioxidant activity methanol (1 : MS, HPLC activities 1) Authors [134] [82] [82, 138] [82, 138, 139] [82, 138–140] [82, 134, 138] [134] [134] [136, 139, 141] [136, 141] [136, 142] [134, 136, 141] 20 Evidence-Based Complementary and Alternative Medicine Table 4: Continued. Name of the compound identiﬁed Chemical class Part Solvent used used Chloroform : methanol (1 : 1) Rt, Methanol SB Ether Ethyl acetate Abyssinone V (59) Flavanone Abyssinone VI (60) Isoﬂavone NS Ether Abyssinone VII (61) Chalcone Rt Chloroform : methanol (1 : 1), ether Erythribyssin N (62) Benzofuran SB Methanol Sigmoidin K (63) Benzofuran SB Methanol Isosojagol (64) Benzofuran SB Methanol Erythribyssin F (65) Coumestan SB Methanol Eryvarin Q (66) Coumestan SB Methanol Erypoegin F (67) Coumestan SB Methanol Erythribyssin H (68) Benzofuran SB Methanol Eryvarin R (69) Benzofuran SB Methanol Erythribyssin E (70) Isoﬂavanone RB Ethyl acetate Prostratol C (71) Isoﬂavanone RB Ethyl acetate Erythribyssin J (72) Isoﬂavanone RB Ethyl acetate 5-Deoxyabyssinin II (73) Flavanone RB Ethyl acetate 7-Demethylrobustigenin (74) Isoﬂavone Rt Chloroform : methanol (1 : 1) Erythribyssin K (75) Flavanone RB Ethyl acetate Erythrabyssin II (76) Pterocarpan Rt Chloroform : methanol (1 : 1), methanol Techniques used Bioactivity Result Authors tested Antimicrobial, UV, NMR, antiplasmodial, HMBC, antioxidant. Weak activity [82, 134, 136, 141–143] HREI-MS, and PTP1B CD, HPLC, inhibitory NOESY activities Antifungal Not reported [136] UV, HPLC activity UV, NMR, Antimicrobial EI-MS, and antioxidant Good activity [134, 136] HMBC, activities HPLC HPLC, IR, Marked [144] UV, MS, AMPK activity stimulation NMR HPLC, IR, Marked [144] UV, MS, AMPK activity stimulation NMR HPLC, IR, Less [144] UV, MS, AMPK activity stimulation NMR HPLC, IR, Marked [144] UV, MS, AMPK activity stimulation NMR HPLC, IR, Less [144] UV, MS, AMPK activity stimulation NMR HPLC, IR, Marked [144] UV, MS, AMPK activity stimulation NMR HPLC, IR, Less [144] UV, MS, AMPK activity stimulation NMR HPLC, IR, Less [144] UV, MS, AMPK activity stimulation NMR PTP 1B Strong IR, UV, MS, [142] inhibitory activity CD, NMR activity PTP 1B IR, UV, MS, Strong inhibitory [142] CD, NMR activity activity PTP 1B Strong IR, UV, MS, [142] inhibitory activity CD, NMR activity PTP 1B IR, UV, MS, Strong [142] inhibitory CD, NMR activity activity UV, NMR, Antimicrobial and antioxidant Weak activity [134] EI-MS, activities HMBC PTP 1B IR, UV, MS, inhibitory No activity [142] CD, NMR activity Antimicrobial Good radical scavenging, (antibacterial) UV, NMR, [134, 136] antiyeast and and radical HPLC antifungal scavenging activities properties Evidence-Based Complementary and Alternative Medicine 21 Table 4: Continued. Name of the compound identiﬁed Chemical class Techniques Part Solvent used used used Liquiritigenin (77) Flavanone RB Ethyl acetate IR, UV, MS, CD, NMR Liquiritigenin-50-Omethyl ether (78) Flavanone RB Ethyl acetate IR, UV, MS, CD, NMR Burttinone (79) Flavone SB Methanol UV, NMR, CD, HRMS Burttinonedehydrate (80) Flavone SB Methanol UV, NMR, CD, HRMS Erythribyssin G (81) Flavanone RB Ethyl acetate IR, UV, MS, CD, NMR Erythribyssin I (82) Flavanone RB Ethyl acetate IR, UV, MS, CD, NMR 7-Hydroxy-4′-methoxy-3prenylisoﬂavone (83) Isoﬂavone SB Methanol UV, FTIR, TLC, NMR, HMBC Coumaric acid Rt Erythrabyssin I (85) Pterocarpan NS Erythrabyssin II (86) Pterocarpan Rt Genistein (87) Isoﬂavone Rt, Tw Neobavaisoﬂavone (88) Flavanone Rt Semilicoisoﬂavone B (89) Isoﬂavone Rt Sigmoidin A (90) Flavanone SB Sigmoidin B (91) Flavanone Rt Sigmoidin B 4’-(methyl ether) (92) Flavanone SB Octacosyl-E-ferulate (erythrinasinate A) (84) Chloroform : UV, NMR, EI-MS, methanol (1 : HMBC 1) UV, NMR, EI-MS, Ether, 80% HMBC, MeOH HPLC Chloroform : UV, NMR, EI-MS, MeOH (1 : HMBC, 1), 80% HPLC MeOH Chloroform : UV, NMR, EI-MS, methanol (1 : HMBC 1) Chloroform : UV, NMR, EI-MS, methanol (1 : HMBC 1) Chloroform : UV, NMR, EI-MS, methanol (1 : HMBC 1) UV, HPLC HREI-MS, HMQC, Methanol HMBC, NOESY NMR UV, NMR, Chloroform : HREI-MS, methanol (1 : HMBC, 1) NOESY UV, HPLC HREI-MS, HMQC, Methanol HMBC, NOESY NMR Bioactivity tested PTP 1B inhibitory activity PTP 1B inhibitory activity PTP 1B inhibitory activity PTP 1B inhibitory activity PTP 1B inhibitory activity PTP 1B inhibitory activity Antimicrobial and antiplasmodial activities Antimicrobial and antioxidant activities Result Authors No activity [142] No activity [142] Good activity [138] Good activity [138] Weak activity [142] No activity [142] Moderately active [145] Weak activity [134,145] Antifungal activity Good activity [134, 136, 141] Antimicrobial and antioxidant activities Moderate activity [134, 136, 141] Antimicrobial and antioxidant Weak activity activities Antimicrobial and antioxidant Weak activity activities Antimicrobial and antioxidant Weak activity activities [134] [134] [134] Antilipase activity Exhibited antilipase activity [82, 146] Antimicrobial and antioxidant activities Good activities [82, 134] Not tested Not applicable [82] 22 Evidence-Based Complementary and Alternative Medicine Table 4: Continued. Name of the compound identiﬁed Chemical class Techniques Part Solvent used used used Phaseolin (93) Chalcone NS Phaseollidin (94) Chalcone Rt Erythrartine/11methoxyerysodine (95) Alkaloid Sd Caryolane-1,9-diol (96) Sesquiterpene Rt Abyssaponin A (97) Triterpenoid SB Abyssaponin B (98) Triterpenoid SB Soyasapogenol B (99) Triterpenoid SB Abyssinoside A (100) Flavanone SB Abyssinoside B (101) Flavanone SB Abyssinoside C (102) Flavanone SB Abyssinoside D (103) Flavanone SB Schaftoside (104) Flavanone SB Isoschaftoside (105) Flavanone SB Vicenin-2 (106) Flavanone SB Hovetrichoside C (107) Aurananol SB Ether UV, NMR, HMBC, EIMS, HPLC Bioactivity tested Result Authors Antimicrobial activity Good activity (antiyeast and antifungal activities) [134, 136, 141] Chloroform : UV, NMR, Antimicrobial methanol (1 : HMBC, EI- and antioxidant Weak activity activities MS, HPLC 1), ether TLC, MS, Anti-HIV-1 and Weak activity Chloroform UV, NMR, cytotoxicity Chloroform : UV, NMR, Antimicrobial methanol (1 : HMBC, EI- and antioxidant Weak activity activities MS, HPLC 1) NMR, UV, Anticancer Strong HRESIEthanol activity activity TOFMS, ESI-MS/MS NMR, UV, Anticancer Strong HRESIEthanol activity activity TOFMS, ESI-MS/MS NMR, UV, Anticancer Strong HRESIEthanol activity activity TOFMS, ESI-MS/MS NMR, UV, Anticancer Moderate HRESIEthanol activity activity TOFMS, ESI-MS/MS NMR, UV, Anticancer Moderate HRESIEthanol activity activity TOFMS, ESI-MS/MS NMR, UV, Anticancer HRESIWeak activity Ethanol activity TOFMS, ESI-MS/MS NMR, UV, Anticancer Moderate HRESIEthanol activity activity TOFMS, ESI-MS/MS NMR, UV, Not HRESIEthanol Not tested applicable TOFMS, ESI-MS/MS NMR, UV, Not HRESINot tested Ethanol applicable TOFMS, ESI-MS/MS NMR, UV, Not HRESINot tested Ethanol applicable TOFMS, ESI-MS/MS NMR, UV, Not HRESINot tested Ethanol applicable TOFMS, ESI-MS/MS [134, 136] [59] [134] [147] [147] [147] [147] [147] [147] [147] [147] [147] [147] [147] Evidence-Based Complementary and Alternative Medicine 23 Table 4: Continued. Techniques Part Solvent used used used UV, NMR, Chloroform : HREI-MS, HMBC, Sigmoidin C (108) Flavanone Rt methanol (1 : 1), methanol NOESY, HPLC UV, NMR, Chloroform : HREI-MS, Rt, HMBC, methanol (1 : Sigmoidin F (109) Flavanone SB HPLC, 1), methanol NOESY HRMS, Quercetin (110) Flavone RB Acetone NMR, HMBC FTIR, UV, 5,4′-di-ODCM: EI-MS, Methylalpinumisoﬂavone Isoﬂavone RB MeOH NMR (111) HRMS, Erycristagallin (112) Pterocarpan RB Acetone NMR, HMBC HRMS, Shinpterocarpin (113) Pterocarpan RB Acetone NMR, HMBC Chloroform : UV, NMR, EI-MS, Sandwicensin (114) Pterocarpan Rt methanol (1 : HMBC 1) Chloroform : UV, NMR, EI-MS, 3,6-Caryolanediol (115) Sesquiterpenes Rt methanol (1 : HMBC 1) Chloroform : UV, NMR, EI-MS, Clovane-2,9-diol (116) Sesquiterpenes Rt methanol (1 : HMBC 1) 7-Hydroxy-2-[4IR, UV, MS, methoxy-3-(3-methylbutFlavanone RB Ethyl acetate CD, NMR 2-enyl) phenyl] chroman4-one (117) UV, NMR, CD, HREIChloroform : MS, HPLC, Rt, methanol (1 : Sigmoidin E (118) Flavanone HMQC, SB 1), methanol HMBC, NOESY UV, CD, Sigmoidin G (119) Flavanone SB Methanol NMR, HRMS Name of the compound identiﬁed 9-Ethyldodecyl-4methoxybenzoate (120) Chemical class Benzoate ester SB Methanol Lupinifolin (121) Flavonoid SB Methanol Kaempferol 3-O-(2-O-bD-glucopyranosyl-6-O-aL-rhamnopyranosyl-b-Dglucopyranoside (122 Flavonol Fl Methanol (acidiﬁed) Bioactivity tested Result Antimicrobial and antioxidant Weak activity activities [82,134] Antimicrobial and antioxidant Weak activity activities [82, 134] Radical scavenging properties Moderately active [133] Antimicrobial activity Not active [137] Radical Moderately scavenging active properties Radical Moderately scavenging active properties Antimicrobial and antioxidant Weak activity activities Antimicrobial and antioxidant Weak activity activities Antimicrobial and antioxidant Weak activity activities PTP 1B inhibitory activity Strong activity Weak Antimicrobial, antimicrobial antioxidant and and PTP 1B antioxidant inhibitory activities, no activities activity PTP 1B inhibitory No activity activity Moderate Antibacterial TLC, NMR and termicidal antibacterial activity activity Moderate Antibacterial TLC, NMR and termicidal antibacterial activity activity NMR, DQF-COSY Authors Not tested Not applicable [133] [133] [134] [134] [134] [142] [82, 134, 138, 139] [138, 139] [62] [62] [148] NS: not speciﬁed; Fl: ﬂowers, Sd: seeds; SB: stem bark, Rt: roots; RB: root bark; Tw: twig; FTIR: Fourier transform infrared spectroscopy; ESI-MS/MS: electron spray ionization tandem mass spectrometry; HRESI-TOFMS: high-resolution electron spray ionization time-of-ﬂight mass spectrometry; HMBC: heteronuclear multiple bond correlation spectroscopy; HMQC: heteronuclear multiple quantum coherence spectroscopy; CD: circular dichroism spectroscopy; HRMS: high-resolution mass spectrometry; NOESY: nuclear overhauser eﬀect spectroscopy; DQF-COSY: double quantum ﬁltered correlation spectroscopy; UV: ultraviolet-visible spectroscopy; MS: mass spectrometry; NMR: nuclear magnetic resonance; TLC: thin-layer chromatography; AMPK: adenosine monophosphate-activated protein kinase. 24 Evidence-Based Complementary and Alternative Medicine trans isomers. The presence of pterocarpans has been attributed to their synthesis by members of the family Fabaceae in response to infections by microorganisms as defense molecules [157]. Eleven pterocarpans (13, 16, 23, 76, 85, 86, 93, 94, and 112–114) were isolated from the roots and root bark of E. abyssinica [133, 134, 136, 141]. (3) Terpenoids (Sesquiterpenes and Triterpenoids). Sesquiterpenes are terpenoids with ﬁfteen carbons (C15) consisting of three isoprene units. They are the dominant constituents of essential oils and other pharmacologically active oxygenated hydrocarbons occurring in higher plants. They naturally exist as hydrocarbons or oxygenated derivatives of hydrocarbons such as carbonyl compounds, alcohols, lactones, and carboxylic acids [158]. Three sesquiterpenes, 3,6caryolanediol (115) and clovane-2,9-diol (116) along with caryolane-1,9-diol (96), were isolated from E. abyssinica roots [134]. On the other hand, two new triterpenoids, abyssaponin A (97) and abyssaponin B (97) along with a triterpenoid saponin, soyasapogenol B (99), were isolated from E. abyssinica stem bark [147]. 3.5. Pharmacology of E. abyssinica and Isolated Compounds. In this section, we report investigations which evaluated the pharmacological potential of both extracts and isolated pure compounds from E. abyssinica. Indeed, phytochemicals in this species possess antibacterial, antifungal, antiviral, anticancer, antioxidant, anti-inﬂammatory, antimycobacterial, anti-HIV/AIDS, antiplasmodial, antihelmintic, antiobesity, antipyretic, antidiabetic, antianemic, and hepatoprotective bioactivities (Tables 4 and 5). 3.5.1. Anti-Inﬂammatory Activity. The aqueous root bark of E. abyssinica at doses less than 100 mg/kg showed considerable in vivo anti-inﬂammatory activity against Trypanosoma brucei-induced inﬂammation in mice [50]. The extracttreated group had a lower number of astrocyte reactivity and reduced perivascular cuﬃng than the nontreated mice. It was suggested that the extracts reduced the inﬁltration of the inﬂammatory cells into the cerebrum of the brain. The antiinﬂammatory activity was attributed to the alkaloids and ﬂavonoids present in the extracts although the pure compounds responsible were not identiﬁed [50]. Interestingly, other crude extracts and pure compounds isolated from members of the genus Erythrina have been validated to possess good anti-inﬂammatory activities via diﬀerent mechanisms. For example, the ethyl acetate and ethanol extracts of E. latissimi, E. caﬀra, and E. lysistemon showed good anti-inﬂammatory activity through reduction in the synthesis of prostaglandins as a result of inhibition of cyclooxygenase activity [168]. Erycristagallin isolated from E. mildbraedii inhibited leukotriene synthesis via the 5-lipoxygenase pathway, thereby demonstrating in vitro anti-inﬂammatory activity (IC50 � 23.4 μM) in polymorphonuclear leukocytes [169]. Three ﬂavonoids (abyssinone V, erycrystagallin, and 4′-hydroxy-6,3′,5′-triprenylisoﬂavonone) isolated from the methanolic stem bark extract E. variegate had strong phospholipase A2 (PLA2) inhibitory activity with IC50 values of 6, 3, and 10 μM, respectively [170]. This implied that these compounds can signiﬁcantly reduce the synthesis of arachidonic acid and consequently diminish the synthesis of prostaglandins and leukotrienes. Two prenylated ﬂavanones (sigmoidin A and sigmoidin B) isolated from E. sigmoidea were reported to selectively inhibit 5-lipoxygenase but had no eﬀect on cyclooxygenase-1 activity. Sigmoidin A had a doseresponse inhibitory potency (IC50 � 31 mM). In the PLA2induced mouse paw oedema assay, only the sigmoidin B inhibited oedema formation with a percentage inhibition of 59% compared to cyproheptadine (positive control) which had 74% after 60 minutes. In the TPA test, both compounds reduced the induced oedema by 89% and 83%, respectively. It was suggested that the compounds had diﬀerent mechanisms of action depending on whether one or two prenyl groups were present in ring B of the ﬂavonoid [83]. Since these same compounds have been isolated from E. abyssinica, it is highly probable that the reported anti-inﬂammatory activity of this plant is due to one or a combination of these mechanisms. 3.5.2. Antioxidant Activity. The in vitro 2, 2-diphenyl-1picrylhydrazyl (DPPH) radical scavenging assay has been widely used to evaluate the antioxidant activity of various phytochemicals and extracts. The ethanolic extract of E. abyssinica (10–320 μg/mL) showed dose-dependent DPPH radical scavenging that was comparable to that of ascorbic acid (a known antioxidant) [159]. Abyssinone VII, sigmoidin B, eryvarin L, and 3-methylbutein isolated from the stem bark and root wood of E. abyssinica showed considerable DPPH radical scavenging potency (IC50 � 12–52 μg/mL) although the standard antioxidants (ascorbic acid, gallic acid, and quercetin) had superior activity (IC50 � 4–18 μg/mL) [134]. The acetone crude extract of the root bark of E. abyssinica (IC50 � 7.7 μg/mL) and two isolated pterocarpenes, erycristagallin (IC50 � 8.2 μg/mL) and 3-hydroxy-9-methoxy-10-(3,3-dimethylallyl) pterocarpene (IC50 � 10.8 μg/mL), showed DPPH radical scavenging activity in a dose-dependent manner similar to that of quercetin (IC50 � 5.4 μg/mL) [133]. The radical scavenging activity of these compounds is due to their free phenolic groups which can donate electrons to the radicals [171]. For ﬂavonoids, the O-dihydroxyl structure in the B ring, the 2,3double bond in conjunction with the 4-oxo function in the C ring, and the 3- and 5-hydroxyl groups with hydrogen bonding to the keto group are responsible for the antioxidant activity. In pterocarpans, the 3,3-dimethylallyl groups enhance the radical scavenging activities and also increase the lipophilicity of these compounds making them better antioxidants than polar ﬂavonoids [133]. 3.5.3. Anticancer Activity. The chloroform, methanol, and ethyl acetate extracts showed cytotoxic activity against diﬀerent tumor cells (cervical, liver, laryngeal, colon, and breast) and strongly inhibited protein tyrosine phosphatase (PTP1B) activity with IC50 ranging between 1 and 100 μg/ mL. Using the dimethylthiazol-2,5-diphenyl-tetrazolium Evidence-Based Complementary and Alternative Medicine 25 Table 5: Pharmacological proﬁle of diﬀerent parts of E. abyssinica. Activity Model used Plant part Extract/ compound Bioassay Results Extract showed dosedependent DPPH radical scavenging activity that DPPH radical Ethanol, Leaves, root bark Antioxidant In vitro scavenging assay was comparable to that of methanol ascorbic acid at all doses (10–320 μg/mL) After 1 h, the DPPH radical scavenging activity was as follows: abyssinone VII: IC50 � 25 μg/mL, Abyssinone sigmoidin B: VII IC50 � 18.5 μg/mL, DPPH radical Sigmoidin B Stem bark Antioxidant In vitro eryvarin L: IC50 � 29 μg/ scavenging assay Eryvarin L mL, and 3-methylbutein: 3IC50 � 37 μg/mL, ascorbic Methylbutein acid: IC50 � 18 μg/mL, gallic acid: IC50 � 4 μg/ mL. and quercetin: IC50 � 7 μg/mL After 30 minutes, the DPPH radical scavenging activity was as follows: crude extract: IC50 � 7.7 μM, abyssinone IV: 32.4 μM, abyssinone V: 30.1 μM, abyssinin III: DPPH radical Antioxidant In vitro Acetone Root bark 21.7 μM, erycristagallin: scavenging assay IC50 � 8.2 μM, 3-hydroxy9-methoxy-10-(3,3dimethylallyl) pterocarpene: IC50 � 10.8 μM, and quercetin: IC50 � 5.4 μM The aqueous extracttreated group (50 mg/kg) had lower astrocyte reactivity (34,545 astrocytes/mm3) than the untreated group (69,886 astrocytes/mm3). Also, they had a reduced degree Methanol Chronic of neuroinﬂammation trypanosomiasis(1.2) compared to the induced Anti-inﬂammatory In vivo Root bark neuroinﬂammation untreated group (2.8). The extract was thought to mouse model reduce the inﬁltration of inﬂammatory cells into the cerebrum. The methanol extract did not have a signiﬁcant Water eﬀect on the modulation of neuroinﬂammation 38% inhibition factor Oral glucose tolerance assay using against hyperglycemia at a Antihyperglycemic In vivo Root bark Water male guinea pigs dose of 500 mg/kg (6 mg/ (Cavia porcellus) kg glibenclamide � 49.6%) Author(s) [127,159] [134] [133] [50] [114] 26 Evidence-Based Complementary and Alternative Medicine Table 5: Continued. Activity Model used Antihyperglycemic In vivo Plant part Extract/ compound Leaf Ethanol Anticancer In vitro Stem bark Ethanol Anticancer In vitro Seeds Chloroform Bioassay Results After 4 hours of Oral glucose tolerance assay using hyperglycemia induction, the extract signiﬁcantly male and dose dependently reduced the mean blood glucose; 100 mg/kg � 25%, Wistar albino rats 200 mg/kg � 46.4%, 400 mg/kg � 60.7%, and 5 mg/kg glibenclamide � 35.7% Compounds exhibited PTP1B inhibitory activity with IC50 values ranging from 4.2 to 19.3 μM and strong cytotoxic activity with IC50 values from 5.6 MTT and protein to 28.0 μM tyrosine After 72 hours of phosphatase exposure; MCF7: (PTP1B) inhibitory IC50 � 19.4 μM, MCF/ assay AMR: IC50 � 12.0 μM, MCF/ADR: IC50 � 16.1 μM, MDAMB-231: IC50 � 28.0 μM, and PTB1B: IC50 � < 30 μM. The crude alkaloidal fraction showed cytotoxic activity against the tumor cells with IC50 values of 13.8, 10.1, 8.16, 13.9, 11.4, and 12.2 μg/mL against HeLa, Hep-G2, HEP-2, HCT116, MCF-7, and HFB4 cells, respectively. After 72 hours of exposure, the IC50 of Sulforhodamine B isolated compounds on assay using HeLa, Hep-G2 and HEP-2 cells Hep-G2, HEP-2, were as follows, HCT116, MCF-7, respectively: erythraline: and HFB4 cells IC50 � 21.60 and 15.8 μg/ mL, erysodine: IC50 � 19.90 and 11.8 μg/ mL Erysotrine: IC50 � 21.60 and 15.8 μg/mL, 8oxoerythraline: IC50 � 18.50 and 3.89 μg/ mL, 11methoxyerysodine: IC50 � 11.50 and 11.4 μg/ mL Author(s) [159] [160] [59] Evidence-Based Complementary and Alternative Medicine 27 Table 5: Continued. Activity Model used Plant part Extract/ compound Bioassay Antianaemic In vivo Stem bark Water extract Phenyl hydrazine anaemia-induced mouse model Antiobesity In vitro Stem bark Sigmoidin A Pancreatic lipase and alpha-glucosidase inhibition assay Methanol Smart button data loggers using ovariectomized rats using Antipyretic and estrogenomimetic In vivo Stem bark Hepatoprotective In vivo Stem bark Water Nonalcoholic fatty liver disease model using rats to evaluate the fasting blood glucose, insulin tolerance, hepatic triglycerides, serum biochemistry, and liver histology Wound healing In vivo Leaf and stem bark Methanol Wound incision assay Results Improved haematinic activity in a dosedependent manner. Extracts increased the red blood cell diﬀerentials in anaemic rats at increasing doses of 50, 100, and 350 mg/kg IC50 � 4.5 and 62.5 μM for pancreatic lipase and alpha glucosidase inhibition, respectively (orlistat � 0.3 μM, acarbose � 190.6 μM) At a dose of 200 mg/kg, the extract reduced the average number of hot ﬂushes (171 in treated vs. 264 in the untreated group). The treated group also had shorter durations of hot ﬂushes (683 minutes) compared to the untreated (1935 minutes) The extract had signiﬁcant eﬀects on fasting blood glucose as well as hepatic indices including liver weights, hepatic triglycerides, liver weightbody weight ratio, serum AST, serum ALT levels, serum triglycerides, serum total cholesterol, and serum LDLcholesterol; however, the extracts showed no signiﬁcant eﬀects on HDL-cholesterol. At high doses (400 mg/kg), the extract protected the liver against inﬂammation, steatosis, and hepatic ballooning 82.1 and 88.7% wound area healed after 15 days for the stem bark and leaf extract, respectively, at a dose of 10% w/w The mean skin protein was 32.5 and 35.5% for the stem bark and leaf, respectively (oxytetracycline � 40.5%). Although the leaf extract had better healing properties than the bark, there was no signiﬁcant diﬀerence between both extracts and the negative control Author(s) [128] [146] [161] [162] [94] 28 Evidence-Based Complementary and Alternative Medicine Table 5: Continued. Model used Plant part Antiplasmodial In vivo Stem and root bark Antiplasmodial In vitro Leaves Antiplasmodial In vitro Stem Antiplasmodial In vivo Stem and root bark Antiviral In vitro Seeds and stem Antimycobacterial In vitro Stem bark Activity Extract/ compound Bioassay Results % chemosuppression: 4-day ANKA root (49.7%), stem Acetone suppressive bioassay (44.2%), and chloroquine using P. berghei (97.3%) n-Hexane Nonradioactive Dichloromethane antiplasmodial 3H After 24 hours, n-hexane extract: IC50 � 0.0 μg/mL, hypoxanthine (DCM) inhibition assay DCM extract: using P. falciparum IC50 � 190.1 μg/mL, multidrug-resistant methanol extract: Indochicha I (W2) Methanol IC50 � 348.2 μg/mL, and chloroquinemeﬂoquine: sensitive Sierra IC50 � 19.2 μg/mL. Leone I (D6) After 24 hours, ethyl Ethyl acetate acetate extract: D6: extract IC50 � 7.9 μg/mL, W2: Nonradioactive antiplasmodial 3H IC50 � 5.3 μg/mL, hypoxanthine chalcones: IC50 ranged inhibition assay from 10 to 16 μM, Isolated using P. falciparum ﬂavanones: IC50 ranged compounds multidrug-resistant from 4.9 to 13.6 μM, (chalcones, Indochicha I (W2) isoﬂavonoids: IC50 ranged ﬂavanones, and chloroquinefrom 18.2 to 24.9 μM, isoﬂavonoids) sensitive Sierra chloroquine: IC50 ranged Leone I (D6) from 0.009 to 0.08 μM, and quinine: IC50 ranged from 0.04 to 0.21 μM At 50 mg/kg of the extract, % chemosuppression: root bark (77%), stem bark (32%), and 10 mg/kg chloroquine (6%). Four-day ANKA suppressive bioassay Survival time in extractMethanol using P. berghei and treated and chloroquinetreated groups was 2- to 3P. falciparum fold higher than the untreated. For P. falciparum, IC50 of 7.81 μg/mL (K1 strain) Stem alkaloidal fraction: IC50 � 53 μM, efavirenz: IC50 � 45 μM MTT assay using Stem had antiviral activity Chloroform, HIV-1-infected MT(reduction factors of the ethanol 4 cells viral titer of 104) against polio, Semliki forest, and herpes viruses At a dose of 2 mg/mL, the extract completely Microdilution assay inhibited the growth of all against Mycobacterial strains (0 Mycobacterium GU). However, at 1 mg/ tuberculosis, mL, there was signiﬁcant Mycobacterium growth of Mycobacterium Methanol kansasii, tuberculosis (19741 GU), Mycobacterium Mycobacterium kansasii fortuitum, and (724 GU), Mycobacterium Mycobacterium fortuitum (174 GU), and smegmatis Mycobacterium smegmatis (4915 GU) Author(s) [163] [145] [49] [28, 164] [59, 112] [165] Evidence-Based Complementary and Alternative Medicine 29 Table 5: Continued. Activity Model used Antimycobacterial In vitro Plant part Root bark Extract/ compound Methanol Bioassay Microdilution assay against pan-sensitive strain (H37Rv), rifampicin-resistant strain (TMC-331), Mycobacterium avium Methanol Antimycobacterial In vitro Stem bark Ethanol Microdilution assay against M. tuberculosis Stem bark Root bark Antihelmintic In vitro Ethanol Worm motility assessment assay on Ascaridia galli Ethanol Worm motility assessment assay on Ascaridia galli Leaves Antihelmintic In vitro Leaves Results Antimycobacterial activity of extract against H37Rv: MIC � 0.39 mg/ mL, TMC-331: MIC � 2.35 mg/mL, Mycobacterium avium: MIC � 0.39 mg/mL. The MICs of isoniazid were 0.25 μg/mL and 9.38 μg/ mL for H37Rv and TMC331, respectively Percentage inhibition of colony formation of diﬀerent combinations: 0.06 μg/mL ethanol extract with 0.01 μg/mL rifampicin and isoniazid � 99.2%, 0.06 μg/mL methanol extract with 0.01 μg/mL rifampicin and isoniazid � 99% and 0.01 μg/mL rifampicin and isoniazid � 86.2% After 24 hours of exposure, at 50 mg/kg of extracts, average number of worms immobilized out of 10: leaf � 9.46, stem � 7.17, root � 7.92, piperazine � 10 At 5% concentration of extracts, average number of worms immobilized out of 10 at diﬀerent times: 12 h � 5, 24 h � 6, 36 h � 9, 48 h � 10 Author(s) [126] [166] [124] [120] 30 Evidence-Based Complementary and Alternative Medicine Table 5: Continued. Extract/ compound Activity Model used Antibacterial Ethanolic extracts inactive against E. coli, S. typhi, and P. aeruginosa. Extracts exhibited diﬀerent antibacterial activities against S. aureus depending on the part of the plant and also the location from where they Microbroth dilution were harvested. In assay against Mbarara, the root extract S. aureus E. coli, was more active (MIC 31.3 mg/mL) than the stem extract (MIC � 3.5 mg/mL). On the other hand, the root extract of Bushenyi was more active (31.3 mg/mL) than that of Ntungamo (4.7 mg/mL). Methanolic extract showed better antibacterial activity (6.0 mm inhibition S. typhi, Bacillus diameter, MIC � 0.23 mg/ cereus, and mL) against S. aureus than P. aeruginosa the positive reference Stem and Ethanol, controls: ampicillin root barks, [19, 26, 91, 123, 127] methanol, In vitro (4.0 mm) and amoxicillin whole plant, chloroform, water (5.0 mm) leaves Chloroform extract of the whole plant had bioactivity against S. aureus, with 7.45 mm inhibition zone diameter Methanolic extract of root bark showed bioactivity against S. aureus, B. cereus, and P. aeruginosa with MIC and MBC of 3.125, 50.00, and 125.00, and 6.25, In vitro antidiarrheal 100.00, and 250.00 mg/ mL, respectively. Aqueous activity extract of root bark showed bioactivity against S. aureus, B. cereus, E. coli, and P. aeruginosa with MIC and MBC of 3.125, 12.50, 250.00, and 125.00, and 3.125, 25.00, 250.00 and 250.00 mg/mL, respectively. Leaf powder exhibited potential antidiarrheal activity in mice. Plant part Bioassay Results Author(s) Evidence-Based Complementary and Alternative Medicine 31 Table 5: Continued. Activity Model used Plant part Antibacterial In vitro Stem and root bark Antibacterial and antifungal In vitro Root bark Extract/ compound Bioassay Results Microbroth dilution assay against Bacillus The extracts were not active on all the bacterial cereus, E. coli, Methanol strains Micrococcus luteus, and P. aeruginosa E. coli and P. aeruginosa: MIC values of all Erythrabyssins I compounds were greater and II than 100 μg/mL; S. aureus: with exception of abysssinone II and VI, Abyssinones I, II, all the other compounds III, IV, V, VI had MIC values below 100 μg/mL. Bacillus subtilis: with exception of abyssinones II and VI, all the other Phaseolin compounds had MIC Microbroth dilution assay against E. coli, values below 100 μg/mL. Penicillium crustosum: S. aureus, Bacillus MIC values of all subtilis, compounds were greater Saccharomyces than 100 μg/mL. cerevisiae, S. cerevisiae and C. utilis: Penicillium with exception of crustosum, erythrabyssin I and P. aeruginosa, phaseolin, all the other Candida utilis, compounds had MIC Mucor mucedo, values above 100 μg/mL. Cryptococcus M. mucedo: with neoformans, and Phaseollidin, Candida albicans exception of erythrabyssin I, abyssinones I and II, extract Phaseolin, all the other compounds had MIC values greater than 100 μg/mL. Extract had eﬀective MICs at 25% (w/v) and 12.5% (w/v) with moderate fungal growth observed at 6.25% (w/v) against C. neoformans and C. albicans Author(s) [100] [60, 141] 32 Evidence-Based Complementary and Alternative Medicine Table 5: Continued. Activity Antibacterial and antifungal Model used In vitro Plant part Stem bark Extract/ compound Bioassay Results Extracts not active on E. coli, weak activity against P. aeruginosa and K. pneumoniae (MIC greater than 50 mg/mL). The methanol extract more active on MRSA (MIC � 6.25 mg/mL) and DCM on S. aureus (MIC � 25.0 mg/mL). Hexane extracts were the least active on all strains. All extracts had good Microbroth dilution activity against assay against E. coli, M. gypseum (MIC less S. aureus, than 12.5 mg/mL) but methicillin-resistant weak activity against S. aureus (MRSA), C. albicans and P. aeruginosa, C. neoformans (MIC Klebsiella Hexane, greater than 100 mg/mL). pneumoniae, dichloromethane, The hexane extract was Microsporum methanol active on gypseum, T. mentagrophytes Trichophyton (MIC � 25.0 mg/mL). mentagrophytes, Lupinifolin and 9C. albicans, ethyldodecyl 2-hydroxyCryptococcus 4-methoxybenzoate from neoformans methanolic extract had zone of inhibition of 9.0 mm each against B. subtilis and E. coli, respectively. The compounds and crude extract inhibited Fusarium spp., Trichophyton spp., and Penicillium spp. with inhibition zones of 9.0–18.0 mm. Author(s) [62, 167] MIC: minimum inhibitory concentration; IC50: inhibitory concentration; GU: growth units. bromide (MTT) assay, the abyssinones A–D and abyssaponins (A and B) isolated from E. abyssinica stem bark exhibited considerable cytotoxicity against MCF-7 and MDA-MB-231 breast adenocarcinoma cell lines with IC50 ranging between 12.9 and 74 μM as compared to resveratrol (IC50 � 13.9–19.3 μM) [147]. The mechanisms by which these phytochemicals mediated their anticancer activity were however not elucidated. However, related phytochemicals isolated from E. suberosa showed to induce apoptosis through the inhibition of NF-kB factor and via an increase in cytosolic cytochrome C that stimulates caspases 9 and 3 which further activates intrinsic apoptosis pathway [172]. 3.5.4. Antidiabetic and Antiobesity Activity. The aqueous extract of this plant showed signiﬁcant antihyperglycemic activity at a dose of 500 mg/kg in rats using the oral glucose tolerance test (OGTT) with a hyperglycemia inhibition factor of 38.5% as compared to glibenclamide (49.6%). It was suggested that probably the inhibition of the SLGT-1 and GLUT-2 transporters along with α-glucosidase were the possible mechanisms for the antidiabetic activity [114]. In an acute OGTT, the ethanolic extract of E. abyssinica signiﬁcantly decreased blood glucose levels in both normal and streptozotocin- (STZ-) induced diabetic rats in a dosedependent manner (100, 200, and 400 mg/kg) when compared with negative (normal saline) and positive control (glibenclamide) [159]. In a subchronic antidiabetic Evidence-Based Complementary and Alternative Medicine test, daily oral administration of the same doses of extract for six weeks signiﬁcantly lowered blood glucose levels in STZ-induced diabetic rats in a dose-dependent manner when compared with the diabetic control group. In this study, glibenclamide (5 mg/kg) signiﬁcantly lowered blood glucose in nondiabetic rats only but not in diabetic rats [159]. Benzofurans, coumestans, and ﬂavanones isolated from the stem bark of E. abyssinica had marked stimulation of the AMP-activated protein kinase (AMPK) activity with varying potencies at 10 μM concentrations with coumestans and benzofurans showing the highest potency. The prenyl groups in coumestans and benzofurans were suggested to be responsible for the enhanced stimulatory activity while their substitution with a methoxy group in the B ring could be responsible for the decreased activation of the AMPK. Activated AMPK plays a critical role in glucose and lipid metabolism such as enhancing insulin sensitivity, stimulating glucose uptake in the muscles, suppressing gluconeogenesis in the liver, increased oxidation of fatty acids oxidation, and diminished fatty acid synthesis. All these mechanisms are responsible for the antidiabetic activity of the isolated phytochemicals [144]. Further, prenylated ﬂavanones from the stem bark of E. abyssinica inhibited protein tyrosine phosphate 1B (PTP1B) activity in an in vitro assay with IC50 values ranging from 15.2 to 19.6 μM compared to RK-682 (positive control, IC50 � 4.7 μM). Since PTP1B regulates the insulin and leptin signaling pathways, its inhibition has been reported to result in hypoglycemic eﬀect, and hence, its inhibitory compounds have a great potential in acting as antidiabetic and antiobesity agents [135, 142, 160]. Sigmoidin A, a ﬂavanone isolated from the stem bark of E. abyssinica showed a considerable in vitro inhibitory activity on pancreatic lipase (IC50 � 4.5 μM) and α-glucosidase enzyme (IC50 � 62.5 μM). Although orlistat (an antiobesity drug) exhibited a superior inhibitory activity against pancreatic lipase (IC50 � 0.3 μM), the observed activity suggested that prenylated ﬂavonoids have potential antilipase activity and hence could be antiobesity agents. Interestingly, its α-glucosidase inhibitory potency was better than that of acarbose (IC50 � 190.6 μM), a standard antidiabetic agent [146]. 3.5.5. Antiparasitic Activity. The antiplasmodial activity of E. abyssinica has been evaluated using the nonradioactive antiplasmodial (in vitro) and four-day Plasmodium berghei ANKA suppressive (in vivo) bioassays [163]. The ethyl acetate extracts had strong in vitro antiplasmodial activity against chloroquine-resistant and chloroquine-sensitive Plasmodium strains with IC50 values of 5.3 and 7.9 μg/mL, respectively [49, 163]. Subsequently, isolated chalcones, ﬂavanones, and isoﬂavonoids had promising antiplasmodial activity against chloroquine-sensitive and chloroquine-resistant P. falciparum strains with IC50 ranging from 4.9 to 24.9 μM although chloroquine still had superior activity [49]. Another earlier in vitro study by Kebenei et al. [143] assessed the possible use of artemisinin in combination with a potential antimalarial drug from ethyl acetate extract of 33 E. abyssinica stem bark reported that abyssinone V isolated from the extract was eﬀective against chloroquine-sensitive (D6) P. falciparum parasites with IC50 value of 3.19 μg/mL. The interaction of artemisinin and abyssinone V analyzed using combination ratios of 10 : 90 to 90 : 10, respectively, against P. falciparum led to the identiﬁcation of an antimalarial combination therapy of artemisinin and abyssinone V with sum of fraction inhibiting concentration (FIC) of 0.79 at a ratio of 2 : 3, respectively [143]. In an in vivo study, the root extracts of this plant suppressed P. berghei infection by 77%, 71%, and 48% in mice treated at 50, 25, and 12.5 mg/kg, respectively. It was also found out that the mice treated with a higher dose (50 mg/ kg) had a signiﬁcantly longer survival time than those treated with lower doses and even chloroquine [164]. The crude leaf extracts of E. abyssinica had weak activity against P. falciparum chloroquine-sensitive Sierra Leone I (D6) and multidrug-resistant Indochicha I (W2) strains with IC50 ranging from 165 to 468 μg/mL [145]. Conversely, erythinasinate A and 7-hydroxy-4′-methoxy-3-prenylisoﬂavone isolated from E. abyssinica methanolic leaf extract had moderate antiplasmodial activity against W2 and D6 with IC50 between 120 and 150 μg/mL [145]. Isolated compounds had a much higher antiplasmodial activity than the crude extract. Isolation removes matrix interference and increases the concentration of the active ingredient at the drug target [173]. In another study, the ethyl acetate extract of this plant at 10 μg/mL inhibited the growth of P. falciparum by 83.6% as compared to chloroquine (98.1%) [73]. This antiplasmodial activity was also conﬁrmed in E. burttii, a related species. The acetone root bark extract of E. burttii had good in vitro antiplasmodial activity against the chloroquine-resistant and chloroquine-sensitive P. falciparum strains with IC50 of 1.73 and 0.97 μg/mL, respectively [163]. The methanolic leaf extract of E. abyssinica also exhibited moderate mosquitocidal and larvicidal activities with 65.5% and 65.1% mortality and corresponding IC50 values of 231.90 and 218.90 mg/mL, respectively. However, the activities were lower compared to that of the standard drug temephos (99.90 %) [49, 145]. The antihelmintic activity of E. abyssinica has been validated using the worm motility assessment assay on Ascaridia galli. The ethanolic leaf extract of this plant at increasing doses up to 50 mg/mL had good antihelmintic activity against A. galli comparable to that of piperazine [124]. At 50 mg/mL, the extract immobilized 95% of the worms as compared to 100% of the standard drug. In another study, 5% concentration of the extract killed all the worms after 48 hours [120]. Although the active phytochemicals were not identiﬁed, it was suggested that the antihelmintic activity of this plant could be due to tannins and alkaloids present in the crude extracts. This is because tannins are polyphenolic compounds like some synthetic antihelmintic drugs such as oxyclozanide and niclosamide. Therefore, the tannins could in a similar way interfere with energy release in the worms through uncoupled oxidative phosphorylation. But also, the tannins could bind to free proteins in the gastrointestinal tract or glycoprotein on the cuticle of the helminth, thereby impairing food absorption, 34 motility, and reproduction. On the other hand, alkaloids being able to stimulate excitatory cells could cause neurological dysfunction that result in paralysis and consequent death of the parasites [124]. 3.5.6. Antibacterial and Antifungal Activities. The antibacterial and antifungal activities of the crude extracts and isolated compounds of E. abyssinica have been widely evaluated using the microbroth dilution assay against various pathogens. The bacteria tested against included Escherichia coli, Staphylococcus aureus, Bacillus subtilis, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi, and Bacillus cereus while the fungi were Micrococcus luteus, Candida utilis, Candida albicans, Mucor mucedo, Saccharomyces cerevisiae, Penicillium crustosum, Microsporum gypseum, Trichophyton mentagrophytes, and Cryptococcus neoformans. The hexane, dichloromethane, ethyl acetate, methanol, and ethanol extracts of this plant showed antibacterial and antifungal activities with minimum inhibitory concentrations (MICs) between 3 and 10,000 μg/mL against diﬀerent pathogens. Generally, the extracts had strong activity against Gram-positive bacteria and moderate to weak activity against Gram-negative bacteria [100, 123, 141, 145, 167, 174, 175]. It was suggested that this could be due to the unique cell wall of Gram-negative bacteria which consists of an additional lipopolysaccharide layer and periplasmic space that make it diﬃcult for antibiotics to penetrate into them. The wide variation in the MIC values could be due to the diﬀerence in the resistance proﬁles of the tested microorganisms with those strains that are more resistant having higher values of MIC compared to the sensitive strains. Although standard drugs had superior activity, isolated pure compounds had higher activity (slightly lower MIC values) than the crude extracts. Flavonoids from the stem bark had MIC ranging between 0.3 and 10 μg/mL against B. subtilis, S. aureus, E. coli, and S. cerevisiae as compared to the antibacterial chloramphenicol (MIC � 0.001–0.5 μg/mL) and antifungal miconazole (MIC � 0.005 μg/mL) [134]. Two pterocarpans and eight ﬂavonoids isolated from the root bark had signiﬁcant activity against S. aureus and B. subtilis with MIC ranging between 6.25 and 50 μg/mL. But moderate activity against many Gram-negative bacterial and fungal strains with MIC greater than 100 μg/mL [141]. Phaseolin and erythrabyssin I showed signiﬁcant antifungal activity (MIC � 6–50 μg/mL) against S. cerevisiae, C. utilis, R. chinensis, and M. mucedo [136]. In a recent study, Schultz et al. [176] reported that ethyl acetate and ethanolic extracts of E. abyssinica bark did inhibit Enterococcus faecium EU-44 (IC50 � 64 μg/mL and MIC > 256 μg/mL), Staphylococcus aureus UAMS-1 (IC50 � 32 μg/mL and MIC 64 μg/mL), Acinetobacter baumannii CDC-0033 (IC50 � > 256 μg/mL and MIC > 256 μg/ mL) but had no activity against Klebsiella pneumoniae CDC004, Pseudomonas aeruginosa AH-71, and Enterobacter cloacae CDC-0032. Further, the extracts did not exhibit quorum sensing above 40% at 16 μg/mL in a quorumsensing inhibition plant extract library screen on S. aureus Evidence-Based Complementary and Alternative Medicine accessory gene regulator I reporter strain [176]. No study reported the mechanism of action of either the extracts or isolated compounds. Therefore, it remains to be determined whether the phytochemicals are microbiostatic or microbicidal. 3.5.7. Antimycobacterial Activity. The crude methanolic root extract of E. abyssinica showed considerable antimycobacterial activity on the rifampicin-resistant (TMC331) and pan-sensitive (H37Rv) Mycobacterium tuberculosis strain with a MIC of 2.35 mg/mL and 0.39 mg/mL, respectively. The MICs for isoniazid were 9.38 and 0.25 μg/mL for TMC-331 and H37Rv, respectively [126]. In another study using the automated BACTEC Mycobacterial Growth Indicator Tube (MGIT) 960 TB system, the methanolic root bark of this plant inhibited the growth of four Mycobacterial strains (M. tuberculosis, M. smegmatis, M. kansasii, and M. fortuitum) at a concentration of 2 mg/mL. Isoniazid, a standard antitubercular drug had a growth inhibitory concentration of 0.5 mg/mL [177]. In a synergistic interaction study, the methanol and ethanol extracts of E. abyssinica (0.49 μg/mL) when combined with either rifampicin or isoniazid (0.01 μg/mL) had a complete inhibitory eﬀect on the growth of M. tuberculosis (H37Rv). The standard drugs and methanol and ethanol extracts at the same tested concentration had innumerous, 125 and 10 colony-forming units [166]. It was postulated that probably the ﬂavonoids, alkaloids, tannins, and terpenoids present in the extracts interacted with the standard drugs at the drug target levels, hence enhancing the activity of each other. The conﬁrmed synergism could be used to explain the concomitant use of herbal medicines alongside the conventional therapies but also reaﬃrms the beneﬁt of combination therapy in the management of susceptible and resistant tuberculosis. Despite the widespread use of E. abyssinica in the traditional management of tuberculosis, we did not ﬁnd any reports on isolation and characterization of compounds from this plant against M. tuberculosis. 3.5.8. Antiviral Activity. The anti-HIV-1 activity of this plant was evaluated using the MTT method. The alkaloidal fraction showed cytotoxicity of HIV-1-infected MT-4 cells with an IC50 of 53 μM compared to efavirenz which had an IC50 of 45 μM. The anti-HIV activity was attributed to the isoquinoline-type alkaloids present in the fraction that inhibit the HIV-1 replication through inhibition of viral entry and reverse transcription processes [59]. The other antiviral activities of this plant have not been validated. However, erysodine, erysotrine, and erythraline isolated from E. cristagalli but also present in E. abyssinica showed signiﬁcant antiviral activity against tobacco mosaic virus (TMV) with IC50 of 1.48, 1.28, and 1.52 μM, respectively, using the leaf disc method. The positive control ningnanmycin had an IC50 of 0.18 μM [178]. Of great interest was the new alkaloid glycoside, erythraline-11-β-O-glucopyranoside which showed a much superior antiviral activity (IC50 � 0.59 μM) against TMV as compared with its aglycone, erythraline (IC50 � 1.52 μM). Evidence-Based Complementary and Alternative Medicine 3.5.9. Antianaemic and Hepatoprotective Activity. The haematinic activity of this plant was evaluated in mice using the phenyl hydrazine-induced anaemic mice model. At doses less than 100 mg/kg, the aqueous stem bark extract of E. abyssinica signiﬁcantly increased the diminished levels of haemoglobin (Hb), red blood cells (RBCs), and packed cell volume (PCV) in mice at the end of four weeks following daily oral administration of the extract. On the other hand, the extract did not have a signiﬁcant eﬀect on the levels of white blood cells, mean corpuscular volume, mean corpuscular haemoglobin, and other diﬀerentials. The observed antianaemic activity was attributed to the ﬂavonoids, alkaloids, and cardiac glycosides present in the aqueous extracts. However, isolation and characterization were not done to identify the pure compounds responsible for this activity. The hepatoprotective eﬀect of the extract was evaluated using the nonalcoholic fatty liver disease (NAFLD) model on rats fed on high-fat and glucose diet. The water extracts at daily oral doses of 200 and 400 mg/kg for 56 days showed signiﬁcant inhibitory eﬀects against the development of nonalcoholic fatty liver disease. The extract was hepatoprotective against steatosis, inﬂammation, and hepatic ballooning. The extracts also signiﬁcantly altered other hepatic-related biochemical indices as compared to standard drug pioglitazone [162]. This hepatoprotective activity was attributed to the coumestans, benzofurans, and pterocarpans present in the water extracts that regulate the activity of AMP kinases and protein tyrosine phosphatase 1B. 3.5.10. Antipyretic and Estrogenic Activity. The estrogenic activity of this plant was studied using the smart button data loggers’ model in ovariectomized rats. The methanol extract (200 mg/kg) and estrogen (1 mg/kg) reduced the number and frequency of hot ﬂushes (171) as compared to those ovariectomized rats that did not receive the extract (264). Also, the rats treated with extract and estrogen had signiﬁcantly reduced durations (683 and 869 minutes, respectively) of hot ﬂashes than the untreated rats (1935 minutes). Thus, the methanol extract seemed to oﬀer protection against small temperature rises which trigger hot ﬂashes in the ovariectomized untreated rats. Although the real chemicals in the extract responsible for the antipyretic activity were not identiﬁed, it was postulated that the chemicals mimic estrogen by increasing the sweating threshold and thermoneutral zone size [161]. In a related study, the estrogenic activity of the erythroidines isolated from E. poeppigiana was evaluated using various estrogen receptor- (ER-) dependent test systems. These included the receptor binding aﬃnity and cell culture-based ER-dependent reporter gene assays. It was found out that both α-erythroidine and β-erythroidine showed signiﬁcant binding aﬃnity values for ERα of 0.015 % and 0.005%, respectively, whereas only β-erythroidine bound to ERβ (0.006 %). In reporter gene assays, both erythroidines showed a signiﬁcant estrogenic stimulation of ER-dependent reporter gene activity in osteosarcoma cells that was detectable at 10 nM in a dose-dependent manner [179]. These 35 erythroidines have also been reported to be present in E. abyssinica and thus could be responsible for the estrogenic activity of this plant. 3.5.11. Anticonvulsant and Anxiolytic Activity. The longknown neuropharmacological activity of this plant was the curariform activity which is largely attributed to alkaloids present in it. Erysodine and erysopine isolated from the seeds of E. abyssinica showed signiﬁcant curare-like activity both in vitro and in vivo [132]. The other CNS demonstrated activities of compounds present in E. abyssinica include anticonvulsant [180, 181], analgesic [180], and anxiolytic. In another study, erysodine and erysothrine (0, 3, or 10 mg/kg) administered orally exhibited anxiolytic eﬀect in mice with comparable eﬃcacy to diazepam (2 mg/kg) administered intraperitoneally. Using the elevated plus maze (EPM) model, only erysodine (10 mg/kg) increased the percentage of open arm entries and open arm time. In the light-dark transition model (LDTM), both erysothrine and erysodine demonstrated anxiolytic-like activity. However, while erysodine (10 mg/kg) increased both times spent in the illuminated compartment and the number of transitions between compartments, erysothrine (3 mg/kg) increased the number of transitions only. It was further observed that none of the two alkaloids neither altered the locomotory behaviour (i.e., the number of closed arm entries) of the animals in the EPM [182]. 3.6. Toxicity Proﬁle of E. abyssinica. Toxicological evaluation of medicinal plants, isolated pure compounds, and corresponding herbal products is one of the key requirements for their approval and licensing as pharmaceutical products by regulatory authorities. This is because apart from possessing pharmacological activity that can be exploited for therapeutic beneﬁts, the same phytochemicals may interact with the same or diﬀerent receptors and elicit toxicity. Some toxicities may either be dose-dependent or dose-independent. On the other hand, some may be immediate while others delayed. Although no substance can be declared to be completely devoid of toxicity, toxicity tests (acute, subacute, subchronic, and chronic) are used to determine the relative toxicity of potential therapeutic agents. Despite the huge data regarding the pharmacological potential of E. abyssinica, there is a paucity of data regarding its toxicity. The seeds are traditionally known to be poisonous [11]. In an in vitro acute toxicity assay using the brine shrimp lethality model, the methanolic and ethanolic extracts of E. abyssinica had LC50 ≥ 1000 μg/mL [127] and 997 μg/mL [159], respectively. A related in vitro study using the haemolytic assay reported that the hexane (62.5 μg/mL), dichloromethane (62.5 μg/mL), ethyl acetate (62.5 μg/mL), and methanol (125 μg/mL) extracts of this plant showed low percentage haemolysis (15.5, 9.1, 15.4, and 39.7%) of red blood cells [175]. The higher percentage haemolysis observed with the methanol extract was attributed to the higher concentration of methanol extract. These in vitro results indicated that the extracts were safe within 24 hours of administration. 36 In a study which determined the in vivo acute toxicity of crude extracts from this plant, it was found out that the median lethal dose (LD50) of leaf and stem bark extracts was above 300 mg/kg body weight. All the mice orally administered with the extracts (100, 200, and 300 mg/kg) survived up to 72 hours and there were no signiﬁcant behavioural changes between the treatment and control groups [183]. In another study, the methanolic root extract was found to have an oral LD50 of 776.2 mg/kg in mice [126]. As with the previous study, acute toxicity signs became more apparent at the highest doses. But still they were limited to sedation and reduced motor activity. Based on the OECD 2001 guidelines, since the LD50 is greater than 300 mg/kg, it can be inferred that the crude extracts are weakly toxic within 24 hours of a single high dose [184]. It is important to know that the seeds of E. abyssinica contain curare-like alkaloids. Thus, it is believed that, at high doses, these may cause anaesthesia, paralysis, and even death by respiratory failure [185]. In a subacute toxicity evaluation of the extract from this plant, the mice were dosed with 100, 200, and 300 mg/kg of the extract daily for 30 days. There was no signiﬁcant difference in behaviour and physical and general activity parameters such as water intake, food consumption, and body weight between the treated groups and control group (no extract given) throughout the period of the experiments [183]. However, there were variations in biochemical parameters between the E. abyssinica-treated groups and nontreated group although it was not statistically signiﬁcant. Particularly the treated group had higher levels of urea and creatinine and lower levels of potassium and sodium. There was also high total and/or conjugated bilirubin associated with E. abyssinica-treated groups. This could probably suggest possible liver insuﬃciency or interference with bile ﬂow. However, this ﬁnding was inconclusive as it could be due to other contributing factors other than the liver. Another study reported that the E. abyssinica (1000 mg/kg) signiﬁcantly increased the levels of urea and creatinine and level of serum diagnostic enzymes particularly alkaline phosphatase, lactate dehydrogenase, gamma-glutamyltransferase, and alpha-amylase in treated mice after 28 days of daily oral administration [128]. This probably indicated some degree of impairment of renal, liver, and heart functions. Histopathological evaluation of the tissues of the liver revealed necrotic foci, dilated and congested blood vessels, numerous hepatocytes with double nuclei in view, and inﬁltration of inﬂammatory cell, while the kidney tissues showed necrotic foci in the papillary region, loss of tubules in necrotic foci, and vacuolated cells in place of original cells. The liver being the primary detoxifying organ of the body while the kidney being the excretory organ are highly susceptible to damage by phytochemicals present in the extracts/herbal medicines. The haematological parameters were also slightly altered by extract administration, suggesting an eﬀect on the hematopoietic tissue [183]. As with the biochemical parameters, the assays did not conclusively show haemolysis or other blood-related toxicity of the extracts. In contrast, another study found out that the stem extract (1000 mg/kg) did not signiﬁcantly alter the haematological indices of the Evidence-Based Complementary and Alternative Medicine treated rats as compared to the nontreated after 28 days of daily oral administration [128]. It can therefore be inferred that extracts of this plant have minimal toxicity eﬀect on the hematopoietic tissue. Since this plant has been reported to have minimal toxicity on the liver, kidney, and hematopoietic tissue, it should be used with caution in traditional medicine. More evidence regarding its chronic toxicity is needed to guarantee its safety especially in the management of chronic conditions. 3.7. Clinical Studies. We did not ﬁnd any relevant report reporting results of a clinical trial on either a pharmaceutical product or an herbal product from E. abyssinica. This could be probably due to the huge ﬁnancial requirement to conduct clinical trials but also other challenges surrounding herbal medicine use. 4. Conclusion and Future Perspectives E. abyssinica has been proven to harbor useful pharmacologically active phytochemicals against various diseases with signiﬁcant eﬃcacies although with some minimal toxicity proﬁles. There is therefore a need to generate more toxicological data about this plant and diﬀerent isolated phytochemicals so as to generate suﬃcient evidence as regards their safety for human use. Once proven safe, the plant could provide a cheap and sustainable source of novel molecules for the development of new therapeutic agents for human ailments. To the best of our knowledge, we did not ﬁnd any E. abyssinica-based pharmaceutical products in the literature, diﬀerent pharmacopoeia, and drug development pipeline. The active phytochemicals identiﬁed could therefore be prioritized and/or optimized for further drug development. There is also a need to standardize and promote rational herbal medicine use through encouraging registration and licensing of products with proven eﬃcacy and safety. Clinical studies utilizing extracts and isolated compounds from E. abyssinica are required. Due to its ethnomedicinal purposes, communities should be sensitized and encouraged to conserve this plant species. Abbreviations AMPK: Adenosine monophosphate-activated protein kinase CNS: Central nervous system E. abyssinica: Erythrina abyssinica Lam. ex. DC. HIV: Human immunodeﬁciency virus LD50: Median lethal dose MIC/IC50: Minimum inhibitory concentration PLA2: Phospholipase A2 WHO: World Health Organization. Data Availability This is a review article and no raw experimental data were collected. All data generated or analyzed during this study are included in this published article. Evidence-Based Complementary and Alternative Medicine Disclosure This work was initially presented at Natural Products Research Network for Eastern and Central Africa Uganda Chapter (NAPRECA-U) in its virtual seminar held on 24 September 2020. Conflicts of Interest The authors declare that there are no conﬂicts of interest regarding the publication of this paper. Acknowledgments The authors are grateful to the World Bank and the InterUniversity Council of East Africa (IUCEA) for the scholarship awarded to SBO, SM, MPO, and TO through the Africa Centre of Excellence II in Phytochemicals, Textiles and Renewable Energy (ACE II PTRE) at Moi University, Kenya, which made this communication possible. Our sincere appreciation goes to the preceding authors for their eﬀorts in sharing their research ﬁndings on the medicinal values of E. abyssinica. This research was supported by the International Foundation for Science (IFS), Stockholm, Sweden, and Organisation for the Prohibition of Chemical Weapons (OPCW) through a grant to Samuel Baker Obakiro (Grant no. I-1-F-6451-1). References [1] D. F. Rambo, R. Biegelmeyer, N. S. B. Toson et al., “The genus Erythrina L.: a review on its alkaloids, preclinical, and clinical studies,” Phytherapy Research, vol. 5, no. 33, pp. 1258–1276, 2019. [2] A. Nyamukuru, J. R. S. Tabuti, M. Lamorde, B. Kato, Y. Sekagya, and P. R. Aduma, “Medicinal plants and traditional treatment practices used in the management of HIV/ AIDS clients in Mpigi District, Uganda,” Journal of Herbal Medicine, vol. 7, pp. 51–58, 2017. [3] F. Schultz, G. Anywar, C. L. Quave, and L. 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