1-s2.0-S0378874115301574-main

Journal of Ethnopharmacology 175 (2015) 648–667

Contents lists available at ScienceDirect

Journal of Ethnopharmacology

http://d0378-87

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journal homepage: www.elsevier.com/locate/jep

Review

Medicinal plants of the genus Anthocleista—A review of theirethnobotany, phytochemistry and pharmacology

Gabriel O. Anyanwu a,c, Nisar-ur-Rehman a,n, Chukwu E. Onyeneke b, Khalid Rauf a

a Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad 22060, K.P.K., Pakistanb Department of Biochemistry, University of Benin, Benin City, Edo State, Nigeriac Department of Biochemistry, Bingham University, Karu, Nasarawa State, Nigeria

a r t i c l e i n f o

Article history:Received 25 May 2015Received in revised form26 September 2015Accepted 28 September 2015

Keywords:AnthocleistaGentianaceaeTraditional usesAntidiabeticAntiplasmodialAntiobesity

Chemical compounds studied in this article:1-hydroxy-3,7-dimethoxyxanthone (Pub-Chem CID: 5488808)3-oxo-Δ4′5-sitosterone (PubChem CID:9801811)6-ketobauerenone (not found)7α-hydroxysitosterol (PubChem CID:161816)anthocleistenolide (not found)anthocleistin (not found)anthocleistol (not found)bauerenol (PubChem CID: 111220)bauerenone (not found)caryophyllene oxide (PubChem CID:6604672)D-(þ)-bornesitol (PubChem CID: 440078)decussatin (PubChem CID: 5378284)de-O-methyllasiodiplodin (PubChem CID:14562693)djalonenol (not found)djalonenoside (not found)djalonensin (PubChem CID: 5360741)djalonensone (PubChem CID:5359485)

x.doi.org/10.1016/j.jep.2015.09.03241/& 2015 Elsevier Ireland Ltd. All rights rese

viations: ACE inhibitors, Angiotensin-convertin Type Culture Collection; ATPase, adenosineEC50, half maximal effective concentration; End inhibition (50% inhibition); LD50, mediannimum inhibitory concentration; PCV, Packedrides; WBC, white blood cellsesponding author.ail addresses: [email protected], [email protected] (C.E. Onyeneke), khalidrauf@ciit.

a b s t r a c t

Ethnopharmacological relevance: The genus Anthocleista of the Gentianaceae family contains 14 species oftrees and shrub-like plants distributed in tropical Africa, in Madagascar and on the Comoros. Tradi-tionally, they are commonly used in the treatment of diabetes, hypertension, malaria, typhoid fever,obesity, diarrhea, dysentery, hyperprolactinemia, abdominal pain, ulcer, jaundice, asthma, hemorrhoids,hernia, cancer, wounds, chest pains, inflammations, rheumatism, STDs, infertility and skin diseases. Theyserve as an anthelmintic, laxative, diuretic and contraceptive. This review aims to provide for the firsttime a repository of ethnopharmacological information while critically evaluating the relation betweenthe traditional medicinal uses, chemical constituents and pharmacological activities of the Anthocleistaspecies so as to unveil opportunities for future research.Materials and methods: A search for relevant information on Anthocleista species was performed onscientific databases (Pubmed, Google Scholar, SciFinder, Web of Science, Scopus, PubChem and other websources such as The Plant List, Kew Botanical Garden and PROTA) and books, PhD and MSc dissertationsfor un-published resources.Results: Out of the 14 species of Anthocleista, 6 have been reported in literature to be widely used in traditionalmedicine for the treatment of various ailments. The six species include: A. djalonensis, A. vogelii, A. nobilis, A.grandiflora, A. schweinfurthii, and A. liebrechtsiana. The chemical compounds isolated from Anthocleista speciesfall into the class of phytochemicals such as secoiridoids, nor-secoiridoids, xanthones, phytosterols, triterpenes,alkaloids, and others of whichmajority of the compounds were isolated from A. djalonensis and A. vogelii. The invitro and in vivo pharmacological studies on the crude extracts, fractions and few isolated compounds of An-thocleista species showed antidiabetic, antiplasmodial, antimicrobial, hypotensive, spasmogenic, anti-obesity,antiulcerogenic, analgesic, anti-inflammatory, antioxidant, antitrypanosomal, anthelmintic, fertility, diuretic andlaxative activities which supports most of their uses in traditional medicine. However, the bulk of the studieswhere centered on the antidiabetic, antiplasmodial and antimicrobial activities of Anthocleista species, althoughthe evidence of its antiplasmodial effect was not convincing enough due to the discrepancies between the invitro and in vivo results.Conclusion: A. djalonensis and A. vogelii are potential antidiabetic and antibacterial agents. The antibacterialpotency relates to infections or diseases caused by E. coli, S. typhi and S. aureus such as urinary tract infections,typhoid, diarrhea, skin diseases, and food poisoning. Pharmacological research on this genus is quite ele-mentary and limited, thus, more advanced research is necessary to isolate and determine the activities ofbioactive compounds in vitro and in vivo, establish their mechanisms of action and commence the process ofclinical research.

& 2015 Elsevier Ireland Ltd. All rights reserved.

rved.

ng enzyme inhibitors; ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate aminotransferase; ATCC,triphosphatase; b.w, body weight; CCl4, carbon tetrachloride; COX, cyclooxygenase; DPPH, 2,2-diphenyl-1-picrylhy-D, effective dose; Hb, hemoglobin; HCD, high carbohydrate diet; HDL-C, high-density lipoprotein cholesterol; IC50,lethal dose, LDL-C, low-density lipoprotein cholesterol; MCH, mean corpuscular hemoglobin; MDA, Malondialdehyde;cell volume; STDs, sexually transmitted diseases; STIs, sexually transmitted infections (STIs); TC, total cholesterol; TG,

[email protected] (G.O. Anyanwu), [email protected] (Nisar-ur-Rehman),net.pk (K. Rauf).

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G.O. Anyanwu et al. / Journal of Ethnopharmacology 175 (2015) 648–667 649

fagaramide (PubChem CID: 5281772)gentianine (PubChem CID: 354616)grandiflorol (not found)grandifloroside (not found)hexadecanoic acid (PubChem CID: 985)humulene epoxide II (PubChem CID:10704181)irlbacholine (PubChem CID: 177983)lichexanthone (PubChem CID: 5358904)lupenone (PubChem CID: 92158)methyl grandifloroside (not found)schweinfurthin (PubChem CID: 643463)scopoletin (PubChem CID: 5280460)secologanin (PubChem CID: 161276)sitosterol (PubChem CID:222284)sitosterol 3-O-β-D-glucopyranoside (Pub-Chem CID: 70699351)stigmasterol (PubChem CID: 5280794)sweroside (PubChem CID:161036)swertiamarin (PubChem CID: 442435)swertiaperennin (PubChem CID: 5281653)ursolic acid (PubChem CID: 64945)vogeloside (not found)α-humulene (PubChem CID: 5281520)β-caryophyllene (PubChem CID: 5281515)

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6492. The classification, botanical description and distribution of Anthocleista . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6503. Ethnomedicinal uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6504. Chemical constituents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6545. Pharmacological activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 654

5.1. Antidiabetic activity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6545.2. Antiplasmodial activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6575.3. Antimicrobial activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6575.4. Antihypertensive and antihypotensive activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6605.5. Spasmolytic and spasmogenic activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6615.6. Anti-obesity activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6615.7. Antiulcerogenic/analgesics, wound healing and anti-inflammatory activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6625.8. Antioxidant activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6625.9. Antitrypanosomal activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6635.10. Anthelmintic activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6635.11. Fertility activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6635.12. Diuretic and laxative activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 663

6. Toxicity studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6637. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 664Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 665References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 665

1. Introduction

The Anthocleista species are trees and shrub-like plants pre-sently in the Gentianaceae family, and formerly of the Loganiaceaefamily, in the major group Angiosperms. The genus Anthocleistacontains about 14 species distributed in tropical Africa, in Mada-gascar and on the Comoros (Leeuwenberg, 1973, 1992; Leeuwen-berg and Leenhouts, 1980; De Wilde, 2011).

The tribe Potalieae includes the genera Anthocleista, Fagraeaand Potalia. The African genus Anthocleista has 15 species, Fa-graea has about 35 species in Southeast Asia, tropical Australiaand the Southwest Pacific; and the American genus Potalia ismonotypic (Punt, 1978). Although Punt (1978) mentioned thatAnthocleista had 15 species, the 14 accepted species inAnthocleista genus include: Anthocleista amplexicaulis Baker,Anthocleista djalonensis A. Chev., Anthocleista grandiflora Gilg,

Anthocleista laxiflora Baker, Anthocleista liebrechtsiana De Wild.& T. Durand, Anthocleista longifolia (Lam.) Boiteau, Anthocleistamadagascariensis Baker, Anthocleista microphylla Wernham,Anthocleista nobilis G. Don, Anthocleista obanensis Wernham,Anthocleista procera Lepr. ex Bureau, Anthocleista scandensHook.f., Anthocleista schweinfurthii Gilg, and Anthocleista vogeliiPlanch (http://www.theplantlist.org/).

Anthocleista are generally called “cabbage tree” in English lan-guage. This is because the stem of some species are unbranched orbranched only at the top with huge leaves clustered at the end ofthe shoot (Keay, 1989). A large proportion of the names used todescribe Anthocleista species seemed to be within the areas orregions of the country in which they are found. For example, in theIjebu land of the western part of Nigeria, Anthocleista spp is calledSapo sapo (Richards, 1939; Ross, 1954). The Hausas (Northern Ni-geria) call it ‘Kwari’ (quiver), the Yorubas (Western Nigeria) call it

http://www.theplantlist.org/

G.O. Anyanwu et al. / Journal of Ethnopharmacology 175 (2015) 648–667650

‘Apa oro’ (Keay Onochie et al., 1964) or sapo and the Ibos (EasternNigeria) call it ‘Mpoto’ (Anyanwu et al., 2013). The local name for A.vogelii in Cameroon is Kewanten (Neba, 2006). Also, it is calledEkoka ngowa (Bakweri) in the Southwest and Littoral region ofCameroun (Jiofack et al., 2010). It is commonly known as ‘Awudifo-Akete’ (murderer’s mat) by the Ashante people in Ghana (Irvine,1961).

Anthocleista has conservative and other traditional uses besidesits medicinal uses. They are a source of food for animals in theforest, such as birds (turacos), ruminants and primates (gorillasand chimpanzees) (Gautier-Hion et al., 1980; Dubost, 1984; Cal-vert, 1985; Basabose, 2002; Babalola et al., 2012). As a tree withrough and coarse bark, Anthocleista is a preferred host for someepiphytes in a tropical semideciduous forest of Ghana (Addo‐For-djour et al., 2009), thereby providing support for this epiphyteswhich are food and habitats for many of the animals inhabiting therainforest canopies. According to Burkill (1985c), the wood-ash ofA. vogelii is used in making dyes, stains, inks, tattoos and mor-dants; the wood is used in carpentry and related applications; thetrunk and branches are used in farming, forestry, hunting andfishing apparatus; the leaf is used in the production of tobacco,snuff, abrasives, cleaners, etc.

The traditional medicinal uses of Anthocleista is in the treat-ment of stomach ache, fever, constipation, inflammatory diseases,diabetes, wounds, etc. (Dalziel, 1955; Ateufack et al., 2014). The useof medical plants is still popular today because they are consideredsafe, less expensive, easily available and effective. The social andeconomic statuses of the people are no barrier to their patronageof herbal medicines in different parts of the world, and mostespecially in developing nations. This review aims to provide forthe first time a repository of ethnopharmacological informationwhile critically evaluating the relation between the traditionalmedicinal uses, chemical constituents and pharmacological activ-ities of the Anthocleista species so as to unveil opportunities forfuture research.

2. The classification, botanical description and distribution ofAnthocleista

The tribe Potalieae is divided into three subtribes: Faroinae,Lisianthiinae, and Potaliinae. The last subtribe, Potaliinae(composed of Fagraea, Anthocleista, and Potalia), was formerlycircumscribed as tribe Potalieae within the family Loganiaceae(Leeuwenberg and Leenhouts, 1980; Struwe et al., 1994). ThePotaliinae are aberrant in Gentianaceae in having fleshy berriesand a preponderance of large trees (Struwe et al., 2002). Thiscontroversy on the family of Anthocleista either in the Logania-ceae or Gentianaceae has been on for decades in the past.

Bremer et al. (1994) and Struwe et al. (1994) had providedfurther evidence that the hypothesis that Loganiaceae sensuLeeuwenberg and Leenhouts (1980) are a paraphyletic assem-blage with members showing closest relationships to otherfamilies both within and outside of the Gentianales as reported(Meszaros et al., 1996). As far as Gentianaceae is concerned,Struwe et al. (1994) main conclusion is to formally includePotalia Aubl., Fagraea Thunb. and Anthocleista Afzel. ex R. Br.(tribe Potalieae of Loganiaceae sensu Leeuwenberg andLeenhouts, 1980) in the Gentianaceae. This transfer had alreadybeen proposed by Bureau (1856), then by Fosberg et al. (1980)on the basis of gross morphology and later by Jensen (1992) onthe basis of the presence of advanced iridoid glucosides asreported (Meszaros et al., 1996).

Anthocleista is presently under the Gentianaceae family butits affinities were previously considered to be with the Logania-ceae (Leeuwenberg, 1992). The phytochemical, morphological and

molecular data of Anthocleista supports its transfer to the Gentia-naceae (Jensen, 1992; Meszaros et al., 1996; Backlund et al., 2000).Therefore, the suitable classification of the genus Anthocleista isthe family Gentianaceae of the order Gentianales.

Generally, Anthocleista is a genus of trees, 6–20 m high or more,trunk 15–55 cm diameter, twigs with spines; leaves opposite, ex-tremely large (up to 150�45 cm2), sessile or very shortly petio-late; lamina dark green and often glossy above; inflorescenceterminal, dichasial or otherwise, large, much-branched; sepals 4,circular or broader than long. Corolla white (or creamy), actino-morphic, thick, fleshy; lobes 8–16, contorted in bud; ovary is su-perior and fruit a berry (Bruce, 1955; Leeuwenberg, 1983; DeWilde 2011; Hyde et al., 2015). However, there are few disparitiesamong the species as observed in their morphology (Punt andNienhuis, 1976; Punt, 1978; Molina and Struwe, 2009; Edwin-Wosu et al., 2015), phylogenetics (Albach et al., 2001) chemotax-onomy (Jensen and Schripsema, 2002; Sonibare et al., 2007); andchemical compounds (Jensen et al., 1975; Jensen, 1992).

Anthocleista species are present in tropical Africa, from SierraLeone in the west to Uganda in the north and to Angola in thesouth (Leeuwenberg, 1983) including Zambia, and Kenya in theEast. Anthocleista species are found in lowland forest and/oraquatic ecosystem. They are perennial trees with marked pre-ference for tropical climates and prevalent in lowland secondaryrainforests. Anthocleista species are common seral plants onabandoned farmland in the forest regions of tropical Africa (Keay,1959). A. djalonensis and A. nobilis show preference for both nor-mal terrestrial (low land dry rainforest) and wetland (seasonallyflooded) environments. A. vogelii shows a preference for normalterrestrial habitat while A. liebrechtsiana prefers wetland or semiaquatic habitats (Edwin-Wosu et al., 2015). A. grandiflora are ri-parian in habitat (Dowsett-Lemaire, 2008).

There is little information about the cultivation of Anthocleistaspecies, as the plants in this genus are not cultivated plants.However, A. vogelii has been reported to be grown by traditionalmedicine practitioners in Osun State, Nigeria (Alade et al., 2011).Aside for its medicinal benefits, the reasons for cultivation of theplant might not exactly be known as the authors did not specify;however, it might not be far from one or all of the reasons men-tioned in the study, which included: easily cultivated, frequentlyused, very costly/scarce in the market, easily perishable and plantsthat must be used fresh (Alade et al., 2011).

3. Ethnomedicinal uses

Out of the 14 species of Anthocleista, 6 have been reported inliterature to be widely used in traditional medicine for the treat-ment of various ailments. The six species include: A. djalonensis, A.vogelii, A. nobilis, A. grandiflora, A. schweinfurthii, and A. lieb-rechtsiana. They are commonly used for treating constipation,malaria fever, typhoid fever, hypertension, stomach aches, he-morrhoids, syphilis, diabetes, and used as a contraceptive, laxativeand purgative (Kadiri, 2009; Musa et al., 2010; Olubomehin et al.,2013). The use of the bark and root of A. vogelii, A. nobilis and A.schweinfurthii as purgative and antidote for snake bite; the bark-sap for ear and eye treatments; and the bark and root in thehealing of dropsy, swellings, edema, gout and venereal diseaseshave been documented (Burkill, 1985a, b and c).

A. vogelii is widely used by traditional medicine practitionerseither singly or in combination with other plant materials to treatseveral diseases or ailments in humans, including infertility pro-blems both in male and female (Oladimeji Igbalaye, Coleshowers2014). Many young women in Nigeria use A. vogelii and in com-bination with other plants as contraceptives usually preferred aftersexual intercourse and before pregnancy (Kadiri, 2009). Root

Table 1Ethnomedicinal uses of Anthocleista species.

Scientific name Local name (ethnic) Country Plant part used Disease condition Preparation form/ Ethnomedicinal receipe Reference

Metabolic disordersA. djalonensis Bheino modyo (P) Guinea Root Diabetes Decoction Diallo et al. (2012)

Sapo (Y) Nigeria Bark Diabetes Maceration with five other plants Soladoye et al. (2012)Sapo (Y) Nigeria Bark, Leaves diabetes ni Olowokudejo et al. (2008)Assoubobissaou (K) Togo Roots, the stem bark,

and the leavesdiabetes Decoction or powder, administrated by oral or anal rout Tchacondo et al. (2012)

A. vogelii Sapo (Y), Kwari (H),Awudifo-Akete (As)

Nigeria, Ghana Root Diabetes Mellitus Decoction Ampofo, (1977), Abuh et al. (1990) andSoladoye et al. (2012)

Ekoka ngowa (Bk) Cameroun Stem bark, Leaves Diabetes Decoction Jiofack et al. (2010)Mpoto (I) Nigeria Root bark Obesity Maceration Anyanwu et al. (2013)

A. nobilis Konibou Kankan (M);Artaninfiro (M)

Guinea Stem bark Diabetes Decoction Diallo et al. (2012)

uko nkirisi (I) Nigeria Root bark Diabetes Mellitus Decoction Madubunyi et al. (1994)

HypertensionA. djalonensis Ezenukpogan (B) Nigeria Leaves and root Hypertension Decoction of the grounded leaves and root with little

water and heat; one spoon taken trice dailyGbolade (2012)

Sapo (Y) Nigeria Roots Hypertension Maceration in combination C. Pilosa, S. Londepedunculataand N. Latifolia/ 1tea spoon 3times daily

Olorunnisola et al. (2015)

Assoubobissaou (K) Togo Roots, the stem bark,and the leaves

Hypertension Decoction or powder, administrated by oral or anal rout Tchacondo et al. (2012)

A. vogelii Benin rope (B) Kwari(H)

Nigeria Stem Hypertension Maceration; soaked in water for 3day; half glass cupdaily

Gbolade (2012)

Diuretic and purgativeA. djalonensis Sapo (Y) Nigeria ni antidiuretic, purgative ni Lawal et al. (2010)A. vogelii ni Africa region,

CamerounStem bark purgative ni Dalziel, (1955) and Adjanohoun et al.

(1986)ni Nigeria Bark and stems Purgative ni Ariwaodo et al. (2012)Urugba (Ig) Nigeria Root/ stem bark Laxative, purgative Boil and drink Okorie, (1976) and Igoli et al. (2005)

A. liebrechtsiana Sapo (Y) Nigeria Bark, Leaves Purgative ni Olowokudejo et al. (2008)

FertilityA. djalonensis Ohangbakire (Ig) Ibu

(In)Nigeria Leaves, Roots and

leavesInfertility (male) A concoction of the three plants is taken once daily.

Decoction of roots and leavesAdjanahoun et al., (1991), Igoli et al.(2005) and Erhabor et al. (2013)

Sapo (Y) Nigeria Bark, Leaves Impotence ni Olowokudejo et al. (2008)Sapo (Y) Nigeria Bark Female infertility ni Soladoye et al. (2014)Assoubobissaou (K) Togo Roots, the stem bark,

and the leavesfemale infertility and maleinfertility

Decoction or powder, administrated by oral or anal rout Tchacondo et al. (2012)

Sapo (Y) Nigeria Bark Hyperprolactinemia Decoction Sharaibi et al. (2014)A. vogelii Sapo (Y) Nigeria Leaf Menstrual Dysfunction ni Omobuwajo et al. (2008)A. nobilis Moukoro (P) Gabon Root Sexual dysfunction Steeping Akoué et al. (2013)

Wudifokεtε/ Hohoroho(A)

Ghana Bark; leaf Protrusion retention duringpregnancy

Decoction Diame (2010)


Ghana Bark Abdominal pains during preg-nancy; menstrual disorders

Decoction Diame (2010)

A. schwein-furthii

Abanga'a Cameroon, Gabon,Equatorial Guinea

Bark Ovarian problems Decoction Kerharo, (1974) and Christophe et al.(2015)

ni Congo Bark female infertility Decoction Schmelzer (2008), Bouquet (1972) Chris-tophe et al. (2015)

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Table 1 (continued )

Scientific name Local name (ethnic) Country Plant part used Disease condition Preparation form/ Ethnomedicinal receipe Reference

ContraceptiveA. vogelii ni Nigeria Roots Contraceptive Maceration with three other plants Kadiri et al. (2009)A. nobilis Wudifokεtε/Hohoroho

(A)Ghana Bark/leaf Contraceptive Decoction Diame (2010)

MalariaA. djalonensis ni Nigeria Leaves, stem bark Malaria ni Ajibesin et al. (2008)

Samatlo (Br) Mali Leaves, roots Malaria Decoction (leaves) or Maceration (roots) Diarra et al. (2015)Côte-d’Ivoire Stem bark Malaria Decoction Zirihi et al. (2010)

A. vogelii Urugba (Ig) Nigeria Leaves/ stem bark Malaria fever Decoctions with five other plants Okorie, (1976) and Igoli et al. (2005)A. nobilis uko nkirisi (I) Nigeria Root bark malaria Decoction Madubunyi et al. (1994)

ni Guinea Root malaria Decoction Baldé et al. (2015)Odeefuor kete (S) Ghana Stem bark and root Malaria Decoction Asase and Oppong-Mensah(2009)ni Côte d'Ivoire Bark Malaria Body smeared with mashed bark Malan et al. (2015)Bomon (G) Guinea Stem bark Malaria Decoction Traore et al. (2013)

A. grandiflora ni Southern Africa Bark Malaria Decoctions Palmer and Pitman (1972)South Africa Stem bark and leaves Malaria Decoction Bapela et al. (2014)

Mbabaigana (KL) Tanzania Leaves, stem barkand roots

Malaria Decoction Nondo et al. (2015)

A. schwein-furthii

ni Tanzania Root Bark and leaves Malaria Decoction Kerharo (1974), Burkill (1995), Fowler(2006), and Christophe et al. (2015)

N.Transvaal Bark Malaria Decoction Fowler (2006)

Stomach disordersA. djalonensis ni Nigeria Roots diarrheoa, dysentery Decoction Akubue et al. (1983), and Nweze and

Ngongeh (2007)A. vogelii ni Africa region,

CamerounStem bark Gastro-intestinal disorders, sto-

mach ache, abdominal painsni Dalziel (1955) and Adjanohoun et al.

(1986)A. nobilis Epo sapo (Y) Nigeria Bark Ulcer Decoction Odukoya et al. (2012)A. schwein-furthii

Bopolopolo (D) Cameroon Stem bark Stomach aches Decoction Etonde and Ekwalla (1997), Kerharo(1974) and Christophe et al. (2015)

A. grandiflora Murigurigu (C) Kenya Stem bark ameba ni Adongo et al. (2012)

Anthelmintic conditionsA. djalonensis Nigeria Roots Worms Decoction Akubue et al. (1983), and Nweze and

Ngongeh (2007)A. vogelii ni Cameroun ni Intestinal worms ni Dibong et al. (2011)A. nobilis uko nkirisi (I) Nigeria Root bark gastrointestinal worms Decoction Madubunyi et al. (1994)A. grandiflora Murigurigu (C) Kenya Stem bark worms ni Adongo et al. (2012)A. schwein-furthii

ni Tanzania Root Bark and leaves worms Decoction Kerharo (1974), Burkill, (1995), Fowler(2006) and Christophe et al. (2015)

Sexually transmitted diseasesA. djalonensis Sapo (Y) Nigeria Root STDs ni Kayode et al. (2004)

Assoubobissaou (K) Togo Roots, the stem bark,and the leaves

syphilis Decoction or powder, administrated by oral or anal rout Tchacondo et al. (2012)

A. vogelii Ekoka ngowa (Bk) Cameroun Stem bark, Leaves STDs Decoction Jiofack et al. (2010)Sapo (Y) Nigeria Leaf Root Gonorrhea Syphilis ni Omobuwajo et al. (2008)Urugba (Ig) Nigeria Root Syphilis/gonorrhea Scrape and squeeze or macerate inner root bark, add salt

and take.Okorie (1976) and Igoli et al. (2005)

Sapo (Y) Nigeria Stem Gonorrhea ni Olukoya et al. (1993)A. nobilis Sapo (Y) Nigeria Root STIs ni Gbadamosi (2014)


STDs (Gonorrhea) Decoction Diame (2010)

A. Abanga'a Cameroon, Gabon, Bark venereal disease Decoction Kerharo, (1974) and Christophe et al.

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schweinfurthii Equatorial Guinea (2015)

Pain, wounds and inflammationsA. djalonensis Sapo (Y) Nigeria Bark, Leaves antipyretic ni Olowokudejo et al. (2008)

Sapo (Y) Nigeria Stem bark Asthma Cold infusion with 8 other plants/ two tablespoon daily Borokini et al., (2013), and Sonibare andGbile (2008)

A. vogelii Ekoka ngowa (Bk) Cameroun Stem bark, Leaves Wounds, Inflammations Decoction Jiofack et al. (2010)Odogwu (Ia) Nigeria Leaves Wounds Applied as poultice on swellings and to cleanse wound Musa et al. (2010)

A. nobilis ni Guinea Root Inflammatory diseases Decoction Baldé et al. (2015)Epo sapo (Y) Nigeria Bark Wounds Hot infusion Odukoya et al. (2012)ni Côte d'Ivoire Root Rheumatism Topical application with crushed roots Malan et al. (2015)

A. grandiflora Murigurigu (C) Kenya Stem bark Chest pains ni Adongo et al. (2012)A. schwein-furthii

ni Tanzania Bark and leaves wound healing Decoction Kerharo, (1974), Burkill (1995), Fowler(2006) and Christophe et al. (2015)

Microbial infectionsA. vogelii Odogwu (Ia) Nigeria Leaves Typhoid fever Decoction Musa et al. (2010)

Sapo (Y) Nigeria Root Throat problems ni Omobuwajo et al. (2008)A. nobilis Wudifokεtε/ Hohoroho

(A)Ghana Bark/leaf Candidiasis/white Decoction Diame (2010)

A. liebrechtsiana Sapo (Y) Nigeria Bark, Leaves antimicrobial Ni Olowokudejo et al. (2008)A. grandiflora Murigurigu (C) Kenya Stem bark cold ni Adongo et al. (2012)A. schwein-furthii

Abanga'a Cameroon, Gabon,Equatorial Guinea

Bark bronchitis Decoction Kerharo (1974) and Christophe et al.(2015)

Mpuku mpuku (Kg) Congo Stem bark Mycosis Crushing Ngbolua et al. (2014a)ni Tanzania Bark and leaves Fever Decoction Kerharo (1974), Burkill (1995), Fowler

(2006) and Christophe et al. (2015)

Skin diseasesA. djalonensis Sapo (Y) Nigeria Bark, Leaves Skin diseases – rashes and eczema ni Olowokudejo et al. (2008)A. liebrechtsiana Sapo (Y) Nigeria Bark, Leaves Skin infection Ni Olowokudejo et al. (2008)JaundiceA. djalonensis Sapo (Y) Nigeria ni Jaundice ni Lawal et al. (2010)A. nobilis uko nkirisi (I) Nigeria Root bark Jaundice, liver protecting effects Decoction Madubunyi et al. (1994)

HemorrhoidsA. djalonensis Assoubobissaou (K) Togo Roots, the stem bark,

and the leaveshemorrhoids Decoction or powder, administrated by oral or anal rout Tchacondo et al. (2012)

A. nobilis Sapo (Y) Nigeria Bark Hemorrhoid Decoction and maceration Soladoye et al. (2010a)Wudifokεtε/Hohoroho(A)

Ghana Leaves Hemorrhoids, piles Infusion/Decoction Diame (2010)

HerniaA. djalonensis Assoubobissaou (K) Togo Roots, the stem bark,

and the leavesHernia Decoction or powder, administrated by oral or anal rout Tchacondo et al. (2012)

A. nobilis Wudifokεtε/ Hohoroho(A)

Ghana Leaves hernia Infusion/decoction Diame (2010)

A. schwein-furthii

ni Congo Bark Hernia Decoction Schmelzer (2008), Bouquet (1972) andChristophe et al. (2015)

CancerA. nobilis Sapo (Y) Nigeria Leaves Cancer Decoction Soladoye et al. (2010b)

A: Akan; As: Ashante; B: Benin; Bk: Bakweri; Br: Bambara; C: Chuka; D: Douala; G: Guerzé; H: Hausa; I: Igbo; Ia: Igala; Ig: Igede; In: Ifa Nkari; K: Kotokoli; Kg: Kikongo; KL: Kagera and Lindi regions; M: Maninka; P: Pular; P: Pygmy;S: Southern Ghana; T: Tumu Fang; Y: Yoruba; ni: not indicated.

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decoctions of A. djalonensis, A. vogelii and A. kerstingii are used inNigeria and Ghana by herbalists for the treatment of diabetesmellitus (Ampofo, 1977). A summary of the ethnomedicinal uses ofAnthocleista species with their local names and methods of pre-paration are presented in Table 1.

4. Chemical constituents

Previous studies on Anthocleista showed the presence of alka-loids, xanthones, secoiridoids, terpenes, and phthalides (Irvine,1961; Chapelle, 1976). Important phytochemicals such as saponins,flavonoids, terpenoids, alkaloids, and steroids are present in theleaf, stem–bark and root bark of A. vogelii (Jegede et al., 2011;Anyanwu et al., 2013; Gboeloh et al., 2014; Ngbolua et al., 2014c).Reducing sugar, tannin, phlobatanins, glycosides were found to beabsent in both the leaf and the stem bark of the Anthocleistaspecies (Njayou et al., 2008; Jegede et al., 2011; Oladimeji Igbalaye,Coleshowers, 2014), however, tannins are present in the root bark(Anyanwu et al., 2013) and anthraquinones in the leaves (Oladi-meji Igbalaye, Coleshowers, 2014).

It has been reported that complex indole alkaloids appear to beabsent in Anthocleista, while secoiridoids and alkaloids derivedfrom these during the isolation procedure are present (Jensen,1992). The secoiridoids found in Anthocleista are typical of thosefound in Gentianaceae species, namely sweroside (1) and swer-tiamarin (2). Secoiridoid glycosides are responsible for the bittertaste of the species. A compilation of the chemical compoundsisolated from Anthocleista species, their structures and class ofphytochemicals which include; secoiridoids, nor-secoiridoids,xanthones, phytosterols, triterpenes, alkaloids, and others is foundin Fig. 1.

The presence of tetraoxygenated xanthones and the secoiridiodglycosides, sweroside (1) and vogeloside, have been reported inthe leaves and roots of A. vogelii (Chapelle, 1976). Sweroside hasrevealed significant anti-inflammatory activity (Baba and Usifoh,2011). Tene et al. (2008) was the first to report the isolation andstructural elucidation of a rearranged nor-secoiridoid, anthocleis-tenolide from the stem bark of A. vogelii. Other chemical com-pounds isolated from A. vogelii include: secologanin (3), decussatin(4), swertiaperennin (6), 1-hydroxy-3,7-dimethoxyxanthone (7),7α-hydroxysitosterol (8), stigmasterol (9), hexadecanoic acid (10),sitosterol 3-O-β-D-glucopyranoside (11), fagaramide (18) and tri-terpenes (Chapelle, 1974; Okorie, 1976; Kojima et al., 1990; Guer-riero et al., 1993; Monte et al., 2001; Valentão et al., 2002; Teneet al., 2008; Alaribe, et al., 2012). Decussatin has demonstratedvery weak antiplasmodial activity (Alaribe et al., 2012). Antho-cleistenolide has revealed low antibacterial activities against S.aureus and E. faecalis while 1-hydroxy-3,7-dimethoxyxanthoneand 1-hydroxy-3,7,8-trimethoxyxanthone showed antifungal ac-tivity against Candida parapsilosis (Tene et al., 2008).

Bierer et al. (1995) reported the isolation and structure eluci-dation of the then novel plant metabolite, 1,22-bis[[[2-(trimethy-lammonium) ethoxy]phosphinyl]oxy]docosane, which theynamed Irlbacholine (23), from the plant species Irlbachia alata andA. djalonensis. Irlbacholine revealed potent in vitro activity againstthree pathogenic fungi: C. albicans, C. neoformans, and A. fumigatus(Biere et al. 1995). Ogunwande et al. (2013) pioneering work on thevolatile oil contents of A. djalonensis revealed sesquiterpenecompounds (82.5%) are the dominant class of the 49 compoundsin A. djalonensis, and the main compounds are α-humulene (20), β-caryophyllene (21), humulene epoxide II (22) and caryophylleneoxide (24). A monoterpene diol, djalonenol have been isolatedfrom A. djalonensis and the isolation of dibenzo-α-pyrone, djalo-nensone (27) from a plant source and it’s structurally elucidationas tetrahydro-3-hydroxy hydroxymethylene-4-(3-hydroxymethylene

prop-1-ene)-2H-pyran-2-one was reported for the first time (Onochaet al., 1995). The isolation of sweroside (1), djalonenoside, lichex-anthone (5), stigmasterol (9), 3-oxo-Δ4′5-sitosterone (12), sitosterol(13), ursolic acid (14), djalonensin (25) and D-(þ)-bornesitol (26)from A. djalonensis have also been reported (Okorie, 1976; Onochaet al., 1995).

Two iridoid glucosides, grandifloroside and methyl grand-ifloroside, one coumarin, scopoletin (27) and the secoiridoidsweroside (1) were found in A. grandiflora (Chapelle, 1973, 1976).Some compounds which have been isolated from the stem bark ofA. grandiflora are grandiflorol, bauerenol (15), bauerenone, 6-ke-tobauerenone; scopoletin (28) and (þ)-de-O-methyllasiodiplodin(29); while lupenone (16) and the iridoid sweroside (1) were ad-ditional compounds isolated from the root bark (Mulholland et al.,2005). Within the other species of Anthocleista much work withregards to isolation has not been done. The investigation of theoccurrence of secoiridoids in methanol extract of the root bark ofA. nobilis by Madubunyi et al. (1994), led to the isolation andidentification of anthocleistol. The secoiridoid swertiamarin (2)have been isolated from A. liebrechtsiana (Cornelis and Chapelle,1976) and bauerenone and bauerenol (15) schweinfurthin (19)from the roots of A. schweinfurthii (Mbouangouere et al., 2007).Although no literature was found on the traditional use of A.procera, phytochemical research on the plant revealed the isola-tion of the secoiridoid swertiamarin (2), the alkaloid gentianine(17) and anthocleistin, a triterpene (Koch et al., 1964; Lavie andTaylor-Smith, 1963; Taylor-Smith, 1965).

5. Pharmacological activities

5.1. Antidiabetic activity

In African traditional medicine, the leaves, stems and roots of A.djalonensis, A. vogelii and A. nobilis are prepared as a decoction ormacerated in water or alcohol, and the solution is given orally as atreatment for diabetes in Guinea, Nigeria, Togo, Ghana and Ca-meroun (Ampofo, 1977; Abuh et al.,1990; Madubunyi et al., 1994;Olowokudejo et al., 2008; Jiofack et al., 2010; Diallo et al., 2012;Soladoye et al., 2012; Tchacondo et al., 2012).

The hypoglycemic effect of the leaves, stem bark and roots of A.djalonensis and A. vogelii, and roots of A. schweinfurthii has beenscientifically proven by in vitro and in vivo studies (Abuh et al.,1990; Olagunju et al., 1998; Mbouangouere et al., 2007; Okokonet al., 2012; Olubomehin et al., 2013; Osadebe et al., 2014a, 2014b;Sunday et al., 2014). The leaves, stem barks and roots of A. djalo-nensis and A. vogelii revealed α-amylase inhibitory activity at 1mLof 250 mg/mL concentration of their aqueous methanol extracts(Olubomehin et al., 2013), although, A. djalonensis had the betteractivity which indicated that it might contain more of the activeprinciples necessary for the management of diabetes. Alpha-glu-cosidase has been effectively inhibited by schweinfurthin, bauer-enone and bauerenol isolated from the dichloromethane/metha-nol extracts of the roots of A. schweinfurthii (Mbouangouere et al.,2007). The inhibition of α-glucosidase and α-amylase by A. djalo-nensis, A. vogelii and A. schweinfurthii prevents the digestion ofcarbohydrates (starch and table sugar), thus serving as potent anti-diabetic agents.

In the in vivo studies, while Olubomehin et al. (2013) reportedhypoglycemic activity of a high dose (1000 mg/kg) of A. djalonensisextracts, Okokon et al. (2012) showed the dose- dependent activityof same plant at lower doses (37 mg/kg, 74 mg/kg and 111 mg/kg).All the doses for other in vivo hypoglycemic studies fell within 37–1000 mg/kg (Abuh et al., 1990; Olagunju et al., 1998; Osadebeet al., 2014b; Sunday et al., 2014), however, results of the variousstudies showed that the extracts/fractions of A. djalonensis and A.

Sweroside (1) Swertiamarin (2)

Iridoids and secoiridoids

Secologanin (3)

Xanthones

Decussatin (4) Lichexanthone (5) Swertiaperennin (6)

1-hydroxy-3,7-dimethoxyxanthone (7)

Phytosterol

7α-hydroxysitosterol (8) Stigmasterol (9) Hexadecanoic acid (10)

Sitosterol 3-O-β-D-glucopyranoside (11) 3-oxo-Δ4'5-sitosterone (12) Sitosterol (13)

Fig. 1. Chemical structures and names of compounds reported from Anthocleista species.


vogelii produced a dose dependent antidiabetic effect (at 100 mg/kg p.o minimum dose) which could justify the use of these plantstraditionally to manage diabetes.

The antidiabetic activity of A. nobilis is yet to be reported de-spite its traditional use in Guinea (Diallo et al., 2012) and Nigeria(Madubunyi et al., 1994). From the existing antidiabetic studies ofA. djalonensis and A. vogelii, the use of solvent fractions of the

plants make it is difficult to know which class of phytochemicalcompounds may be responsible for their antidiabetic effect, exceptbased on polarity. Also, more active compounds should be isolatedfrom the Anthocleista species for the purpose of testing their an-tidiabetic activity. The mechanisms of action of the extracts/frac-tions of these plants are not yet known and no study has beendone on it. Further research is needed to understand how the

senepretirT

)61(enonepuL)51(lonereuaB)41(dicacilosrUAlkaloids Steriod

)91(nihtrufniewhcS)81(edimaragaF)71(eninaitneG

Volatile oil contents

α-humulene (20) β-caryophyllene (21) Humulene epoxide II (22) Caryophyllene oxide (23)

edirahccasogilOedilahthPetilobatemtnalP

)62(lotisenrob-)+(-D)52(nisnenolajD)42(enilohcablrIdibenzo-α seditekyloPniramuoCenoryp-

)92(nidolpidoisallyhtem-O-ed)82(nitelopocS)72(enosnenolajD

Fig. 1. (continued)


plants exert their blood glucose lowering activities; either by in-creasing the amount of insulin secreted by the pancreas, increas-ing the sensitivity of target organs to insulin, and/or decreasing

the rate at which glucose is absorbed from the gastrointestinaltract. So basically research on diabetes for this species is still at itscrude form.


5.2. Antiplasmodial activity

Malaria is a major health problem in Africa caused by Plasmo-dium species transmitted by mosquitos. The Anthocleista speciesare used to treat malaria in countries like Nigeria, Mali, Côte-d’I-voire, Guinea, South Africa and Tanzania, of which the mode ofpreparation is decoction/maceration and administered orally (Ta-ble 1), except in Côte-d’Ivoire where the bark of A. nobilis is ma-shed and smeared on the body (Malan et al., 2015).

Both in vitro and in vivo antiplasmodial studies have been car-ried out on Anthocleista. While the in vivo results were positive, thein vitro results were negative or not impressive among the species.In two different in vitro studies by Zirihi et al. (2005) and Zirihiet al. (2010), A. djalonensis was inactive against Plasmodium falci-parum in culture with IC50 value 450 μg/mL at a concentration of10 mg/mL. Similarly, Bapela et al. (2014) reported that 10 mg/mL ofdichloromethane and methanol extracts of A. grandiflora showedno in vitro antiplasmodial activity (IC50 450 μg/mL). Again,among the 31 plants tested for in vitro antiplasmodial activity byNondo et al. (2015), ethanol extracts of A. grandiflora at 100 μg/mLwas among the least active with growth inhibition rate of less than30% against chloroquine-resistant Plasmodium falciparum Dd2strains. The in vitro antiplasmodial studies on the species seemsinadequate as most where not dose dependent, variation of ex-traction solvents from nonpolar to polar, and the laboratorytechniques were not exhaustive. No in vitro antiplasmodial studieswere found to be reported on A. vogelii and A. nobilis.

As in Table 2, the different plant parts of A. djalonensis, A. vogeliiand A. grandiflora at doses ranging from 50–3000 mg/kg have allrevealed in vivo antiplasmodial activities against Plasmodium fal-ciparum or Plasmodium berghei in a dose dependent manner(Bassey et al., 2009; Alaribe et al., 2012; Odeghe et al., 2012a; Okonet al., 2014; Gboeloh et al., 2014; Ogbuehi et al., 2014). The work byAlaribe et al. (2012) revealed a variation in the route of adminis-tration, where the petroleum ether leaf extracts (50, 100, 250 mg/kg) of A. vogelii produced a dose dependent reduction in parasitedensity compared to the control group when given in-traperitoneally. But, there was no reduction when the extract wasadministered orally at 100–1250 mg/mL in chloroquine sensitivePlasmodium berghei infected mice. It is possible that petroleumether was not efficient in extracting most of the active principlesfrom the plant compared to more polar solvents like ethanol, forwhich antiplasmodial activity was reported when the extractswere given orally.

Odeghe et al. (2012b) reported the effectiveness of the methanolextract of A. grandiflora in increasing the hematological values (PCV,Hb, WBC, platelets, lymphocyte, neutrophils and monocyte) and de-creasing the levels of AST and ALT activities of malaria parasite in-fected rodents. This indicated that the extract possess the ability toenhance blood component to phagocytose, delay or prevent the in-cidence of anemia, protect the liver by its free radical scavengingactivities and improve the disease progression.

Typical of herbal medicines all over the world, is the combi-nation of several plants to treat a particular disease condition,which is a function of the understanding that the active principlesin the different plants work synergistically to elicit the expectedhealing. The combination of A. nobilis, Nauclea latifolia and Napo-leona imperialis and the individual plants exerted antiplasmodialeffect in varying degrees at 125, 250 and 500 mg/kg concentra-tions; however their combination gave improved symptomaticrelief from malaria and extended the mean survival time of thetreated mice (Ogbuehi et al., 2014). Similarly, A. vogelii in combi-nation with Ficus exasperata has been shown to be effective againstP. berghei berghei (Okon et al., 2014).

An isolated compound decussatin (4), from pet ether leaf ex-tract of A. vogelii, demonstrated very weak reduction in parasite

density at 10 mg/kg in P. berghei infected mice. Also, the extractand decussatin demonstrated good iron chelating ability at1 mg/mL concentration which might contribute in its anti-plasmodial activities (Alaribe et al., 2012). So far, decussatin is theonly isolated compound from the Anthocleista species that hasbeen tested for antiplasmodial activity. However, the results of thein vivo studies support the traditional use of the Anthocleistaspecies in the treatment of malaria.

The variation of in vitro and in vivo antiplasmodial results callsfor further research while modifying the extraction solvents orstandard techniques used for the in vitro antiplasmodial studies inorder to determine the most adequate or appropriate. However,the positive in vivo results, and weak/negative in vitro anti-plasmodial results is not a new phenomenon, as such weak/ne-gative results are referred to as false negatives. According toWalker (1987), several examples already exist of nucleoside anti-viral agents which in vitro show weak or negative activity butwork very well in vivo. Furthermore, the identification of thebioactive components in the species responsible for the anti-plasmodial activity should be investigated with the aim of eluci-dating their mechanism of action and exploring the species fornew malaria drugs.

5.3. Antimicrobial activity

The Anthocleista species have been useful in the healing ofcertain diseases caused by microbial infections such as typhoid,candidiasis, mycosis, bronchitis and fever (Table 1). Also, thetreatment of sexually transmitted diseases by Anthocleista speciesis a common herbal practice in countries like Nigeria, Togo, Ca-meroun, Gabon and Equatorial Guinea (Kerharo, 1974; Okorie,1976; Olukoya et al., 1993; Igoli et al., 2005; Omobuwajo et al.,2008; Kayode et al., 2004; Diame, 2010; Jiofack et al., 2010;Tchacondo et al., 2012; Gbadamosi 2014; Christophe et al., 2015).More so, skin diseases such as rashes and eczema are being treatedwith Anthocleista species (Olowokudejo et al., 2008). Usually, theplants are soaked in water or macerated before drinking (Table 1).

Anthocleista species have demonstrated antibacterial activityagainst disease causing microorganisms like Escherichia coli, Sal-monella typhi, Staphylococcus aureus, Klebsiella pneumoniae andCorynebacterium diphtheriae. E. coli is the main causal agent ofurinary tract infection, also causes food poisoning. S. aureus causesboils, impetigo cellulitis, abscesses, wound infections, toxic shocksyndrome, pneumonia, and food poisoning. S. typhi is the majorcause of typhoid, and sometimes accompanied with weakness,headache, abdominal pain and constipation, and in rare casesvomiting and diarrhea. K. pneumoniae causes pneumonia and in-fections in the urinary tract while C. diphtheriae causes diphtheria.These explain the use of Anthocleista species by locals and tradi-tional healers in the treatment of typhoid, diarrhea, skin diseasesand other infections.

Studies have provided scientific evidence for the long use ofthese plants in the treatment of microbial infections (Table 2). A.djalonensis have been shown to possess notable growth inhibitoryactivities against E. coli, E. faecalis, S. typhi, S. aureus, Bacillus sub-tilis, Pseudomonas aeruginosa, Proteus spp., and Shigella spp. (Atin-dehou et al., 2002; Okoli and Iroegbu, 2004; Chah et al., 2006;Akinyemi and Ogundare, 2012; Leke, 2012), but weak antifungalactivity against Candida albicans and Cladosporium cucumerinum(Atindehou et al., 2002). The folkloric claim that A. djalonensis arepotent in the management of tuberculosis and leprosy was in-vestigated in a sensitivity screening study by Esimone et al. (2009).The methanol leaf and root extracts of A. djalonensis showed anti-mycobacterial activity (MIC¼125 μg/mL), while the aqueous ex-tracts of the same parts exhibited no inhibitory activity againstMycobacterium smegmatis (Esimone et al., 2009). This suggests

Table 2Pharmacological activities of Anthocleista species.

Pharmacological activities Scientific name Part used Extract/fraction Dosage/duration Modelused

Type of effect References

Antidiabetic activity Anthocleistadjalonensis

Leaves, stembark and roots

Aqueous methanol (E), hexane (F), ethyl acetate(F)

1 mL of 250 mg/mL in vitro alpha-Amylase inhibitory Olubomehin et al. (2013)

Same same 1 g/kg 7 days in vivo Hypoglycemic Olubomehin et al. (2013)Roots Ethanol (E), methanol (F), chloroform (F), ethyl

acetate (F)37,74, 111 mg/kg 7 h and15 days

in vivo Hypoglycemic Okokon et al. (2012)

Leaves Isosaline (E) 15 days in vivo Hypoglycaemic, hypolipaemic,hypocholestero-laemic activities

Olagunju et al. (1998)

Anthocleista vogelii Leaves, stembark and roots

Aqueous methanol (E) 1 mL of 250 mg/mL in vitro alpha-amylase inhibitory Olubomehin et al. (2013)

Stem bark Methanol (E), chloroform (F), ethyl acetate (F),acetone (F) and water (F)

200 and 400 mg/kg6 hrs

in vivo Hypoglycemic Osadebe et al. (2014b)

Root Ethanol (E and F) 100, 200 and 400 mg/kg in vivo Antidiabetic/ Toxicity Sunday et al. (2014)Root Aqueous (E) 100, 400 and 800 mg/kg in vivo Hypoglycaemic Abuh et al. (1990)

AnthocleistaSchweinfurthii

Root Dichloromethane (E), methanol (E) α-Glucosidase inhibition Mbouangouere et al. (2007)

Spasmogenic activity Anthocleista vogelii Stem bark Aqueous (E), Methanol (E) 0.13–8.00 mg/mL in vitro Spasmogenic Ateufack et al. (2010)Stem bark 1-Hydroxy-3,7,8-trimethoxyxanthone (AV) iso-

lated from the methanol extract2.50�10�2–1.60 μg/mL in vitro Spasmogenic Ateufack et al. (2007)

Anthocleista nobilis Root bark Ethanol (F) 0.06–0.31 mg/ml in vitro Spasmolytic Madubunyi and Asuzu(1996)

Cardiovascular effect Anthocleista nobilis Root bark Aqueous (E), alcohol-insoluble fraction of theaqueous extract

Up to 1 mL/kg in vitro Hypotensive Activity Duwiejua (1983)


Root bark Aqueous (E), dichloromethane (E), cardiac glyco-side type compounds (F)

in vitro Vasoconstrictor and inotropiceffects

Ngombe et al. (2010)

Antimalarial Activity Anthocleistagrandiflora

Stem barks Methanol (E) 300, 500, 700 mg/kg 12days

in vivo Hematological and biochemicalIndices

Odeghe et al. (2012b)

Stem barks Methanol (E) 300, 500, 700 mg/kg 12days

in vivo Antiplasmodial activity Odeghe et al. (2012a)

Stem bark Dichloromethane (E) and aqueous (E) 10 mg/mL in vitro Antiplasmodial activity Bapela et al. (2014)Stem bark Ethanol (E) 100 μg/mL in vitro Antiplasmodial activity Nondo et al. (2015)

Anthocleistadjalonensis

Leaf Stem bark Ethanol (E) 1000–3000 mg/kg/day220–660 mg/kg/day

in vivo Antiplasmodial activity schi-zontocidal activity

Bassey et al. (2009)

Stem back Ethanol (E) 10 mg/mL in vitro Zirihi et al. (2005) and Zirihiet al. (2010)

Root Ethanol (E) Chloroform (F), ethyl acetate (F) andmethanol (F)

175–1 000 mg/kg; 250and 500 mg/kg

in vivo Antiplasmodial and antipyreticactivities

Akpan et al. (2012)

Anthocleista vogelii Stem back Ethanol (E) 100,200, 400 mg/kg in vivo Antiplasmodial activities (incombination with Ficusexasperata)

Okon et al. (2014)

Leaf Petroleum ether (E) 100–1250 mg/kg p.o,50–250 mg/kg i.p

in vivo Antiplasmodial effect Alaribe et al. (2012)

Decussatin 10 mg/kg in vivo Antiplasmodial effect Alaribe et al. (2012)Stem bark Ethanol (E) 100, 200, and 400 mg/

kgin vivo Antiplasmodial effect Gboeloh et al. (2014)

Anthocleista nobilis Root Methanol (E) 125, 250 and 500 mg/kg in vivo Antiplasmodial effect in combi-nation with two plants

Ogbuehi et al. (2014)

Antiulcerogenic activity Anthocleista vogelii Stem bark 1-hydroxy-3,7,8-trimethoxyxanthone of Methanol 1, 2, and 5 mg/kg in vivo Ateufack et al. (2014)

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–667658

(E)Aqueous (E), hexane (E), acetone (E), Methanol (E) 500 mg/kg in vivo Ateufack et al. (2006)

Antiobesity activity Anthocleista vogelii Root bark Ethanol (E) 500 mg/kg 28 days in vivo Antiobesity Anyanwu et al. (2013)Root bark Ethanol (E) 500 mg/kg 28 days in vivo Liver function, antioxidant

activityAnyanwu Sangodele et al.(2014)

Analgesics properties Anthocleista vogelii Stem bark Aqueous (E) 125, 250 and 500 mg/kg in vitro Analgesic effect Mbianctha et al. (2013)Anthocleistadjalonensis

Root Methanol (E) 200, 400 and 800 mg/kg in vivo Analgesic effect Kagbo and Simon (2015)

Antimicrobial effects Anthocleista vogelii Leaf Aqueous (E), ethanol (E), chloroform (E) 12.5–100 mg/kg in vitro Typhoid fever Musa et al. (2010)Stem Aqueous (E), Ethanol (E) ni in vitro Antimicrobial effect Olukoya et al. (1993)Leaves Acetone (E), ethanol (E), methanol (E), methyle-

nedichloride (E), methanol:chloroform: water (E),water (E)

in vitro Antimicrobial effect Eloff (1998)


stem bark andleaves

n-hexane (F), dichoromethane (F), ethyl acetate(F), and methanol (F)

250–1.95 μg/mL in vitro Antibacterial Ngbolua et al. (2014b)

Anthocleistaliebrechtsiana

stem bark andleaves

n-hexane (F), dichoromethane (F), ethyl acetate(F), and methanol (F)

250–1.95 μg/mL in vitro Antibacterial Ngbolua et al. (2014c)


Leaves Methanol (E), Petroleum ether (E), Aqueous (E) 30–5.0 mg/mL in vitro Antidiarrhoeal effect Akinyemi and Ogundare(2012)

Root Hexane (F) Methanol (F), Chloroform (F), Aqueous(F)

Full length and 10%dilution

in vitro Antimicrobial effect Leke et al. (2012)

Stem bark Ethanol (E) ni in vitro Antibacterial and antifungal Atindehou et al. (2002)Leaves Methanol (E) 3000.00–21.87 mg/mL in vitro Antibacterial Ikegbunam et al. (2014)Root Methanol (E) 0.1 mL of 20 mg/mL in vitro Antibacterial Chah et al. (2006)Root Ethanol (E), cold and hot water (E) 100 μL l of 25 mg/mL in vitro Treatment of STDs Okoli and Iroegbu (2004)Leaves Root Aqueous (E) Methanol (E) 20 mg/mL in vitro Anti-mycobacterial Esimone et al. (2009)

Anthocleista nobilis Stem bark, rootbark

Ethanol (E) ni in vitro Antibacterial and antifungal Atindehou et al. (2002)

Root Ethanol (E) 0.5 mg/100 g for 28 days in vivo Newcastle disease virus Ayodele et al. (2013)Stem bark Methanol (E) 20 μL aliquot of extract in vitro Antibacterial Annan and Dickson (2008)

Fertility Anthocleista vogelii Leaves Ethanol (E) 100, 200 mg/kg in vivo Improve female fertility Oladimeji Igbalaye and Co-leshowers (2014)


Root Ethanol (E) 1 mL in vivo Improve male fertility Muanya and Odukoya(2008)

Anti-inflammatory activity Anthocleistadjalonensis

Root Aqueous ethanol (E) and sweroside 100, 200 and 400 mg/kg in vivo Baba and Usifoh (2011)

Root Methanol (E) 0.2 mL of 20 mg/mL in vitro Wound healing properties Chah et al. (2006)Anthocleista nobilis Stem bark Methanol (E) 33.3% w/w in vivo Wound healing activity Annan and Dickson (2008)

Antitrypanosomal activity Anthocleista vogelii Leaf, stem androot

Aqueous (E), ethanol (E) 2.5–40.0 mg/mL in vitro Abu et al. (2009)


Stem back Ethanol (E) 500–0.07 g/mL in vitro Atindehou et al. (2004)

Anthocleista nobilis Root bark Ethanol (E) 80, 67, 40 mg/kg, i.p. In vivo Madubunyi and Asuzu(1996)

Antioxidant assay AnthocleistaSchweinfurthii

stem bark andleaves

Methanol (F) 0.1–1 mg/mL in vitro DPPH radical scavenging assay Ngbolua et al. (2014b)

Anthocleistaliebrechtsiana

stem bark andleaves

Methanol (F) 0.1–1 mg/mL in vitro DPPH radical scavenging activity Ngbolua et al. (2014c)

Anthocleista Leaves Methanol (E) 100 μL/ various conc. in vitro Free radical scavenging activity Awah et al., (2010)

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Table

2(con

tinu

ed)

Pharmacolog

ical

activities

Scientificnam

ePa

rtused

Extract/fraction

Dosag

e/du

ration

Mod

elused

Typeof

effect

Referen

ces

djalon

ensis

Antho

cleistano

bilis

Bark

Ethan

ol(E)

–in

vitro

TBAreactivity

Oduko

yaet

al.(20

12)

Stem

bark

Methan

ol(E)

50μL

of10

–10

0μg

/mL

invitro

DPP

Hradical

scav

engingactivity

Annan

andDickson

(2008

)

Anthelminticactivity

Antho

cleista

djalon

ensis

Root

Ethan

ol(E)

25–20

0mg/mL

invitro

Nwez

ean

dNgo

nge

h(2007

)

Diuretican

dLaxa

tive

activity

Antho

cleistavo

gelii

Root

bark

Ethan

ol(E)

250–

500mg/kg

invivo

Any

anwuet

al.(un-

published

thesis,2

015)


that the active principles in A. djalonensis are better extracted ormuch more concentrated in alcoholic extracts.

Aqueous, ethanol and chloroform extracts of A. vogelii leaf andstem bark have revealed antibacterial activity against S. typhi, K.pneumoniae and C. diphtheriae (Olukoya et al., 1993; Musa et al.,2010), while the methanol stem bark extracts of A. nobilis inhibitedthe growth of S. aureus, B. subtilis, M. flavus, E. coli and P. aeruginosa(Annan and Dickson, 2008). The extracts of the leaves and stembarks of A. schweinfurthii and A. liebrechtsiana have shown anti-bacterial activity against S. aureus, but they were less sensitive to E.coli (Ngbolua et al., 2014b, 2014c). Species like A. schweinfurthiiand A. liebrechtsiana have only been screened for fewer micro-organisms, there is need to experiment with more microorganismsin order not to limit the effect of the plants. Traditionally, A.schweinfurthii is used to treat bronchitis and mycosis, but there isyet to be scientific evidence to this practice.

Irlbacholine, isolated from A. djalonensis, revealed potent invitro activity against three pathogenic fungi: C. albicans, C. neo-formans, and A. fumigatus, with minimum inhibitory concentra-tions (MIC) of 1.25, 0.04 and 0.08 pg/mL respectively (Biere et al.1995). Similarly, Irlbacholine showed potent activity(MIC¼0.04 pg/mL) against the dermatophyte Trichophyton ru-brum. Tene et al. (2008) evaluated the antibacterial and antifungalactivities of anthocleistenolide, 1-hydroxy-3,7-dimethoxyx-anthone,1-hydroxy-3,7,8-trimethoxyxanthone and sitosterol 3-O-β-D-glucopyranoside isolated from the stem bark of A. vogelii. Theresults showed relatively low activity against Staphylococcus aur-eus (MIC¼200 μg/mL) and against Enterococcus faecalis(MIC¼100 μg/mL) for anthocleistenolide, while compounds 1-hy-droxy-3,7-dimethoxyxanthone and 1-hydroxy-3,7,8-trimethoxyx-anthone were active against Candida parapsilosis with MIC of200 μg/mL and 25 μg/mL respectively. Sitosterol 3-O-β-D-gluco-pyranoside was inactive against all the bacterial and fungal speciesused.

Although, the traditional use of Anthocleista species for thetreatment of STDs and skin diseases still remains to be provenscientifically, their use in the treatment of bacterial and fungaldiseases have been sufficiently supported by the above scientificstudies. However, more work is essential to isolate the biologicallyactive components in the numerous extracts for antibacterial andantifungal activities. Studies on antiviral activities of this specieswere not found to be reported.

5.4. Antihypertensive and antihypotensive activities

In Nigeria and Togo, the leaf, bark and root of A. djalonensis andA. vogelii are used to treat hypertension (Table 1). The root of A.djalonensis is also macerated in combination with three otherplants (Crematogaster pilosa, Securidaca londepedunculata andNauclea latifolia) and one tea spoon is taken three times daily totreat hypertension in Nigeria (Olorunnisola et al., 2015). Although,no comprehensive ethnobotanical use of A. nobilis and A.schweinfurthii for the management of hypertension was found,Burkill (1985a and 1985b) had earlier documented the traditionaluse of the leaf of A. nobilis for the treatment of spasm, and the leaf,bark and root of A. schweinfurthii as medicines for arteries andveins. The reason behind the tradition use of Anthocleista speciesin the treatment of hypertension might not be farfetched as stu-dies have suggested their action on adrenergic receptors, direct orindirect activation of L-type calcium channels, antispasmodic ef-fect, vasodilator action, inhibition of the Naþ pump, ganglion-blocking and muscarinic effect (Lafon, 1966; Duwiejua, 1983; Ig-nesti et al., 1988; Ngombe et al., 2010).

The pharmacological effects of the aqueous extract and thealcohol-insoluble fraction (crystalline compound) of the aqueousextract of the root bark of Anthocleista nobilis was investigated on


the arterial blood pressure of anaesthetized cat and on isolatedperfused rabbit heart by Duwiejua (1983). A dose-dependent de-pressor effect, which was slightly antagonized by atropine, wasobserved in both models (in vitro and in vivo). The extract exerteda resultant lowered tone of the muscles which could cause a dropin the blood pressure. The hypotensive action of the root extract ofA. nobilis was reported to be due to a direct muscarinic effect,ganglion-blocking effect and a non-specific depressant action onboth smooth and skeletal muscles.

Previously, Lafon (1966) reported that the aqueous and alcoholextracts of A. nobilis possess antispasmodic effect, hypotensiveactivity, neurotropic activity and vasodilator action. Also, aqueousextract of A. nobilis has been reported to have inhibited the con-traction induced by noradrenalin in the rat ductus deferens (Ig-nesti et al., 1988). Vasodilation involves the widening of arterialand/or venous vessels, thus reducing systemic vascular resistanceand consequently leading to reduced blood pressure. The vasodi-lator effect of A. nobilis validates its traditional use for the man-agement of hypertension or spasms.

Ngombe et al. (2010) investigated the cardiovascular effect ofthree extracts (aqueous extract, dichloromethane extract and afraction enriched in cardiac glycoside type compounds) from theroot bark of A. schweinfurthii. The bolus injection of extracts pro-duced a positive inotropic effect in isolated perfused frog heart.Other results indicated that A. schweinfurthii contains substancesthat promote vasoconstriction and increase cardiac contraction.The effect of dichloromethane extract was only partially mediatedby inhibition of the Naþ pump while the mechanism of action ofaqueous extract and cardiac glycoside type compounds was dis-tinct from the inhibition of the Naþ , Kþ-ATPase pump, but couldinvolve adrenergic receptors, or either direct or indirect activationof L-type calcium channels. The rise in concentration of Ca2þ ionswithin vascular smooth muscle cells results in vasoconstriction(Capponi et al., 1985). Drugs/agents that cause vasoconstriction,that is the narrowing of blood vessels (large arteries and smallarterioles) help to elevate blood pressure. Therefore, the vaso-constrictor effect of A. schweinfurthii suggests its possible use forthe treatment of hypotension.

Scientific reports supporting the traditional use of A. djalonensisand A. vogelii for the management of hypertension was not avail-able. Recent studies on the hypotensive properties of Anthocleistaspecies is lacking, and neither past nor the reported studies havegone beyond fractions in their investigation of the species. Thisspells out clearly that more work on the pharmacological activitiesof the extracts, fractions and their isolated compounds isnecessary.

5.5. Spasmolytic and spasmogenic activities

The traditional use of Anthocleista species in the treatment ofstomach disorders such as stomach ache, abdominal pains, ulcer,diarrhea and dysentery has been reported (Dalziel, 1955; Akubueet al., 1983; Adjanohoun et al., 1986; Nweze and Ngongeh, 2007;Adongo et al., 2012; Odukoya et al., 2012; Christophe et al., 2015).Generally, the relevant parts of A. djalonensis, A. vogelii, A. nobilis,A. schweinfurthii, and A. grandiflora are prepared by decoction andtaken orally in Nigeria, Cameroun and Kenya (Table 1).

In evaluating the pharmacological properties of defatted etha-nol root bark extract A. nobilis, Madubunyi and Asuzu (1996) tes-ted its spasmolytic effect on smooth muscle, the isolated guinea-pig ileum. Out of six fractions obtained by chromatographic se-paration of the ethanol extract, only one fraction, which showedone main compound (Rf 0.4) in chloroform:acetone:formic acid(9:2:1) relaxed the guinea-pig ileum in a concentration-dependentmanner. This indicated that the active principle responsible for therelaxation effect on the guinea-pig ileum was contained in the

polar fraction of the extract. The spasmolytic activity of A. nobilissupports its traditional use in the treatment of colic, stomach-aches, diarrhea and constipation. Although, neither the compoundnor mechanism by which A. nobilis produces spasmolysis havebeen investigated.

Ateufack et al. (2010) have reported the spasmogenic effect ofA. vogelii stem bark, where it’s aqueous and methanol extractsproduced a dose-dependent effect on the tone and force of thespontaneous contraction of the rat ileal and stomach smoothmuscle fragments at concentrations ranging from 0.13 to8.00 mg/mL. Also, xanthone, 1-hydroxy-3,7,8-trimethoxyxanthoneisolated from the methanol extract of the stem bark of A. vogeliiproduced a dose-dependent effect on the tone and force of thespontaneous contraction of the rat ileal and stomach smoothmuscle fragments at concentrations ranging from 2.50�10�2 to1.60 mg/mL (Ateufack et al., 2007). These results point to a possiblestimulation of these muscle fragments through muscarinic re-ceptors which increase Ca2þ mobilization from both extra andintramuscular medium, that is, the plant extracts or isolatedcompound interfere with calcium metabolism in smooth muscle toexert its effect. The spasmogenic activity of A. vogelii validates theiruse in African traditional medicine for gastro-intestinal disorders,stomach ache and as a purgative, and most especially for thetreatment of abdominal pains in Cameroon.

The suggestion by the authors that the spasmogenic effect ofaqueous and methanol extracts of A. vogelii is by stimulation ofmuscarinic receptors needs further investigation to ascertainwhich muscarinic receptor subtypes (M1–M5) and their location isresponsible for this function. Also, it is imperative to determine ifthe stimulation of muscarinic receptors extends to other smoothmuscles like the heart, mesenteric arteries, veins, etc. This is im-portant because, for instance, activation of M1 and M3 are knownto mediate a direct smooth muscle vasocontrictive effect whichconsequently leads to elevated blood pressure (Medina et al., 1997;Grekin and Hamlyn, 2003). But it is also possible that the aqueousand methanol extracts of A. vogelii might act by stimulating M2muscarinic receptors in the heart and aorta of animals therebyproducing hypotension. If such is the case, this action may alsolend support to the use of A. vogelii in the management of hy-pertension by traditional healers and locals (Table 1).

The evidences above support the use of A. nobilis and A. vogeliifor their folkloric use against stomach disorders, but no evidencewas available to support the traditional use of A. djalonensis fordiarrhea or dysentery; A. schweinfurthii for stomach aches or A.grandiflora for stomach amoeba infections (Table 1).

5.6. Anti-obesity activity

The impact of ethanol extract of A. vogelii root bark on weightreduction in high carbohydrate diet (HCD) induced obesity in malewistar rats had been investigated. The ethanol extract of A. vogeliiof 500 mg/kg b.w significantly decreased food intake, body weight,total fat mass, adiposity index, low density lipoprotein cholesterol,glucose and leptin levels (Anyanwu et al., 2013). In an anti-lipi-deamic study in hyperglycemic rats, the ethanol root extracts (100,200 and 400 mg/kg) and fraction (200 mg/kg) of A. vogelii exerteda dose dependent significant decrease (Po0.05) in TC, TG, LDL-C,ALT, AST and an increase in HDL-C when compared to the control(Sunday et al., 2014).

The ethanol extract of A. vogelii root bark showed positive effecton liver function and antioxidant status of obese rats (Anyanwuet al., 2014). The extract of 500 mg/kg b.w significantly decreasedALT, AST and ALP activities; while it increased the catalase andsuperoxide dismutase activities, and glutathione level, with nosignificant difference in MDA level compared to the high fat dietand high carbohydrate diet obese controls. Also, the numerous


prominent fat deposits in the livers appeared relatively reducedamong the groups treated with the extract (Anyanwu et al., 2014).These indicated that the ethanol extract of A. vogelii root bark washelpful in preventing the progress of oxidative stress, fatty liverand eventually obesity.

Although, the results of the antiobesity studies which werelimited to A. vogelii seemed interesting, none of the studies havedetermined the antiobesity effect of Anthocleista species based onthe 5 categorized mode of action for antiobesity agents fromnatural products. This means that the species need to be tested fortheir ability to decrease energy intake, increase energy ex-penditure, decrease lipid absorption, decrease lipogenesis and in-crease lipolysis, and lastly to decrease pre-adipocyte differentia-tion and proliferation. Also, studies need to go beyond crude ex-tracts and fractions of plants, beginning with in vitro studies whichare lacking if any meaningful antiobesity agents have to be dis-covered from this species.

5.7. Antiulcerogenic/analgesics, wound healing and anti-in-flammatory activities

The antiulcerogenic effect of a drug often times is as a result ofits combined effect of decreasing both pain and inflammation. Theethnomedicinal uses of A. vogelii in the treatment of stomach painhave been validated by the findings that both aqueous and organicextracts of the stem bark of A. vogelii possess potent antiulcerproperties. The aqueous and methanol extracts showed 87.91% and100% inhibition respectively at a dose of 500 mg/kg whenscreened for antiulcerogenic activity using HCl/ethanol gastricnecrotizing solution (Ateufack et al., 2006). Similarly, the aqueousextract at a dose of 500 mg/kg significantly reduced in-domethacin-induced gastric lesions by 78.62% while the methanolextract at the same dose completely inhibited the action of in-domethacin (Ateufack et al., 2006). Further investigations on theaction of the xathone (1-hydroxy-3,7,8-trimethoxyxanthone) ob-tained from the methanol extract of the A. vogelii stem bark pre-vented in a dose-dependent manner ulcers induced by HCl/etha-nol (60.90–93.22%), Indometacin (46.86–89.68%), and pylorus li-gation (0.00–70.69%) at the doses of 1, 2, and 5 mg/kg respectively(Ateufack et al., 2014).

Anti-inflammatory agents/drugs make up about half of an-algesics, because they remedy pain by reducing inflammation orswelling. Traditionally, a cold infusion of the stem bark of A. dja-lonensis with 8 other plants is prepared and two table spoons istaken daily for the treatment of Asthma in Nigeria (Sonibare andGbile, 2008; Borokini et al., 2013). For swellings, rheumatism andwounds, the area affected is poulticed to relieve the soreness andinflammation, and to cleanse the wound (Musa et al., 2010).

The action of A. djalonensis at central and peripheral sites toinhibit neurogenic and inflammatory pains has been proposed byKagbo and Simon (2015), after investigation of the analgesicproperties on the methanol root extract of A. djalonensis in albinorats using chemical, mechanical and thermal models of pain. Theresponse to neurogenic and inflammatory pains by the formalinhind paw licking test was used to study chemically induced pain.Mechanical pain was induced by exertion of pressure on inflamedand hyperalgesic rat paw with an Analgesy-meter while thermallyinduced pain was assessed by the supraspinally mediated tail flicktest. The extract showed a significant, dose dependent inhibitionof nociception in all the models of pain used.

The aqueous extract of A. vogelii stem barks at 125, 250 and500 mg/kg, reduced the number of abdominal constrictions in-duced by acetic acid with 40.42%, 65.62% and 68.75% respectivelydemonstrating its analgesics properties (Mbianctha et al., 2013). Inthe formalin test of the same study, extract provoked 56.48%,59.49% and 89.93% of inhibition respectively with the same doses;

while the second phase was marked by a higher activity of theextract, with 94.16%, 97.47% and 100% of inhibition.

The ethanol-water (1:1) extract of A. djalonensis root showedsignificant activity (po0.05) at 400 mg/kg comparable to the re-ference drug, while the pure compound (sweroside) isolated fromthe extract revealed significant anti-inflammatory activity(po0.05) at 100 mg/kg in animal model (Baba and Usifoh, 2011).Chah et al. (2006) determined the wound healing properties ofmethanol root extracts of A. djalonensis using the excision woundmodel, and the extract proved wound healing properties (98.84%)comparable with that of the standard drug cicatrin

s

(100%) by the17th day post-surgery in rats. Also, the methanol extracts of A.nobilis revealed potent wound healing activity as evident from thewound contraction, increased tensile strength and hydroxyprolinecontent in male rats using the excision wound model (Annan andDickson, 2008).

These findings support the traditional use of Anthocleista spe-cies, particularly A. djalonensis, A. vogelii and A. nobilis as painkillers and in the treatment of wounds and inflammatory diseases.Although, scientific evidence supporting the traditional use of A.grandiflora and A. schweinfurthii for treatment of chest pains andwounds respectively is lacking, based on evidence of other An-thocleista species as anti-inflammatory agents, there is need toresearch their mode of action for reducing pain and/or in-flammation, likewise the bioactive agents mediating these effects.

5.8. Antioxidant activity

Antioxidants are needed to prevent the formation and reducethe level of reactive oxygen and nitrogen species, which are pro-duced in vivo and cause damage to DNA, proteins, lipids, and otherbiomolecules. Antioxidants are widely used in dietary supple-ments and have been investigated for the prevention of diseasessuch as cancer, coronary heart disease and even altitude sickness(Baillie et al., 2009). Plants produce a number of antioxidants fortheir own protection and some that may also be useful to humanssuch as vitamin E, vitamin C, carotenoids, flavonoids, etc. TheAnthocleista species are potential source of antioxidants whichcould be responsible for their health benefits.

The methanol extract of A. djalonensis leaves showed a verypotent DPPH and O2� anion radical scavenging activities(IC50¼8.6970.95 μg/mL and 5.3271.05 μg/mL respectively).Also, the extract displayed significantly higher OH radical and non-enzymatic lipid peroxidation inhibitory potentials than that ofstandard antioxidants (IC50¼33.0675.65 μg/mL and59.1474.64 μg/mL respectively), likewise, it inhibited the accu-mulation of nitrite in vitro (Awah et al., 2010). Annan and Dickson(2008) reported the inhibition of lipid peroxidation, DPPH radicalscavenging activity and protection against oxidant injury to fi-broblast cells as indications of A. nobilis potent antioxidant activity.

A. Schweinfurthii and A. liebrechtsiana had been shown to pos-sess DPPH free radical scavenging activities (IC50o10 μg/mL)(Ngbolua et al., 2014b, 2014c). And the ethanol extract of Antho-cleista nobilis bark showed TBA reactivity by decreasing levels ofMDA and a reduction in lipid peroxides both in the raw andcooked fish homogenate, but the antioxidant capacity was lowcompared to other plants tested (Odukoya et al., 2012).

The extract of A. schweinfurthii showed no inhibition of mi-crosomal lipid peroxidation using rat hepatic microsomes, butrevealed inhibition of carbonyl-group formation on bovine serumalbumin (BSA), that is, against protein oxidation. The results in-dicated that the antioxidant activities of A. schweinfurthii may bedue to their ability to scavenge free radicals involved in proteinoxidation, but not in microsomal lipid peroxidation (Njayou et al.,2008). Nonetheless, the compounds within the plants that areresponsible for its antioxidant properties are yet to be identified.


5.9. Antitrypanosomal activity

The antitrypanosomal activity of 101 crude ethanol extractsderived from 88 medicinal plants from Cote d’Ivoire was de-termined in vitro using Trypanosoma brucei rhodesiense by Atin-dehou et al. (2004). A. djalonensis was one of the 56 plants that didnot show any activity at all (IC50 values 425 g/mL). Similarly, in aprevious study, the defatted ethanol root bark extract of A. nobilisdid not reduce the level of parasitaemia in mice infected withTrypanosoma brucei brucei (Madubunyi and Asuzu, 1996). How-ever, a different result was obtained in the in vitro anti-trypanosomal studies of crude extracts of some Nigerian medicinalplants by Abu et al. (2009). It was discovered that both aqueousand ethanol extracts of the root bark of A. vogelii showed activityat 40 and 20 mg/mL, but the stem bark had no activity at the testconcentrations. This could be indicative of species difference withrespect to presence or concentration of the bioactive componentsin the part of the plants used.

5.10. Anthelmintic activity

Anthelmintic is any drug used in the treatment of infectionscaused by parasitic worms (helminths). Helminths include tape-worms, roundworms and flukes. The Anthocleista species havebeen used to kill or flush out worms in Tanzania, Nigeria, Camer-oun and Kenya (Table 1). Majorly, the roots and stem barks of theA. djalonensis, A. vogelii, A. nobilis, A. schweinfurthii, and A. grand-iflora are prepared as a decoction and taken orally (Akubue et al.,1983; Kerharo, 1974; Madubunyi et al., 1994; Burkill, 1995; Fowler,2006; Nweze and Ngongeh, 2007; Dibong et al., 2011; Adongoet al., 2012; Christophe et al., 2015).

The in vitro anthelmintic activity of the ethanol extract of A.djalonensis was studied against L larvae of Heligmosomoides poly-gyrus (roundworm) at 25, 50, 100 and 200 mg/mL concentrations(Nweze and Ngongeh, 2007). The extract had a concentration-dependent lethal action on H. polygyrus larvae. At a concentrationof 100 mg/mL, the extract recorded 98.45% mortality which wasequivalent to that of levamisole (the positive control) at 10 mg/mL.This is indicative of the validity of its use traditionally againstworms and other internal parasites in the body, and thus, themode of action of the species on the worms needs to beinvestigated.

5.11. Fertility activity

The Anthocleista species, particularly A. djalonensis, A. vogelii, A.nobilis and A. schweinfurthii are a source of traditional recipes fortreatment of male and female fertility problems in Togo, Nigeria,Ghana, Cameroon, Gabon, Equatorial Guinea and Congo (Table 1).Traditionally, A. djalonensis is used in South West Nigeria to boostlibido, induce erection, increase sperm count and consequentlymale fertility (Olowokudejo et al., 2008). Other examples includethe use A. vogelii for the treatment of menstrual dysfunction(Omobuwajo et al., 2008) and A. schweinfurthii for ovarian pro-blems (Kerharo, 1974; Christophe et al., 2015). In contrast to theuse of Anthocleista species to enhance fertility, the roots of A. vo-gelii and bark/leaf of A. nobilis are reported to be used as contra-ceptives or to induce abortion (Kadiri, 2009; Diame, 2010).

Reactive oxygen species are important mediators of spermdysfunction (Wang et al., 1997; Bansal and Bilaspuri, 2011). Pro-duction of MDA, an end product of lipid peroxidation, has beenreported in spermatozoa. Muanya and Odukoya (2008) studied theeffect of 9 medicinal plants on lipid peroxidation as an index ofmale fertility. Lipid peroxidation in raw and cooked fish homo-genates was measured as the amount of thiobabituric acid reactivesample (TBARS) in nmol/mg. The A. djalonensis extract was the

most active in the inhibition of lipid peroxidation among the9 plants tested. This indicates that A. djalonensis possess the abilityto improve sperm function thereby increasing male fertility, andhereby it gives support to its traditional use in the treatment ofmale fertility problems.

The ethanol extract of A. vogelii showed a statistically sig-nificant increase of estradiol concentration in the female rats, from(184.65730.06 pg/mL) in the control group compared to(288.29730.06 pg/mL) in the extract treated group (OladimejiIgbalaye, Coleshowers, 2014). In female reproductive system, es-trogen plays a very important role especially in ovulation. Theevidence by Oladimeji Igbalaye and Coleshowers (2014) that A.vogelii can induce estrogen production supports the claim on thetraditional use of the plant to enhance fertility in females.

The traditional use of A. djalonensis for the treatment of femaleinfertility has not been reported, likewise no report was found forA. nobilis and A. schweinfurthii vis-à-vis its folkloric use for im-proving female fertility. Nevertheless, the evidence that A. djalo-nensis and A. vogelii improves male and female fertility respec-tively should trigger further investigation on the bioactive com-pounds in these plants in order to develop them into useabletherapeutic agents of fertility enhancers.

5.12. Diuretic and laxative activities

Traditionally, A. djalonensis, A. vogelii, and A. liebrechtsiana areused as purgative by locals/natives in Nigeria, Cameroun and otherAfrican regions (Dalziel, 1955, Okorie, 1976; Adjanohoun et al.,1986; Igoli et al., 2005; Olowokudejo et al., 2008; Lawal et al.,2010; Ariwaodo et al., 2012). The leaf, bark or roots are usuallyboiled with water and drank to obtain its purgative/laxative effect.The root of A. vogelii is traditionally used as a diuretic (Burkill,1985c), however, Lawal et al. (2010) reported the use of A. djalo-nensis as an antidiuretic.

The diuretic and laxative activity of ethanol extracts of A. vogeliiroot bark was studied in vivo in male wistar rats (Anyanwu et alunpublished thesis, 2015). The extracts increased the volume ofurine excreted compared to the negative control at 250 mg/kg and500 mg/kg oral doses after 5 and 18 h. Diuretics promote theproduction and excretion of urine from the body. A. vogelii provedto be a potent diuretic as it promoted the excretion of urine fromthe rats, although the effect was not more than the positive control(25 mg/kg of Furosemide). Thus, the traditional use of A. vogelii forforced diuresis and hypertension is valid.

In the laxative studies, ethanol extracts of A. vogelii root barksignificantly increased the fecal output of rats compared to thepositive and negative control at 500 mg/kg oral dose after 8 and 16hours (Anyanwu et al unpublished thesis, 2015). A. vogelii wasshown to be a potent laxative at 500 mg/kg, but not at 250 mg/kgconcentration of the extract. As common with all laxatives, A. vo-gelii increased bowel movement and loosened feces. Therefore, theresults supported its traditional use as a laxative or purgative.

Apart from A. vogelii, the diuretic and laxative effect of otherAnthocleista species has not yet been reported. The dose, that is,500 mg/kg at which the diuretic and laxative effect of A. vogeliiwas recorded seems high considering the use by humans, thebiodiversity of the plant will greatly be affected. Also, consideringthat the diuretic effect of A. vogelii at 500 mg/kg was not morethan that 25 mg/kg of Furosemide, there is need to research thebioactive component of the plant, possibly its effect may becomparable or more than the available standard diuretic drugs.

6. Toxicity studies

There are several acute toxicity studies in different animalsshowing different safety levels or varying LD50 of the different


parts of Anthocleista species. The acute toxicity study of aqueousextract of the stem bark of A. vogelii did not provoke a death untilthe dose of 20 g/kg p.o in mice (Mbianctha et al., 2013). The acutetoxicity (LD50) of the ethanol stem bark extract was estimated tobe 3162 mg/kg p.o in mice (Gboeloh et al., 2014). In anothertoxicity study on pet ether leaf extract of A. vogelii, no lethality wasobserved at 2000 mg/kg body weight i.p. in mice (Alaribe et al.,2012). Sunday et al. (2014) reported the LD50 of A. vogelii ethanolroot extract as Z5000 mg/kg p.o in rats, while in an earlier study,the ethanol extract of A. vogelii root bark revealed no lethality at6400 mg/kg p.o in rats (Anyanwu et al., 2013).

The LD50 of the defatted ethanol root bark extract of A. nobiliswas 200 mg/kg, i.p. in mice (Madubunyi and Asuzu, 1996). Theacute toxicity study of the stem bark of A. grandiflora indicated thatextract did not cause mortality of mice up to 1000 mg/kg p.o.(Okoye et al., 2014). Acute toxicity using a single dose of 2000 mg/kg of aqueous extract of A. schweinfurthii bark administered orallyto mice showed neither death nor significant changes in the be-havioral and morphological parameters after 14 days of observa-tion (Christophe et al., 2015).

In a subacute toxicity study, the aqueous extract of the stembark of A. vogelii tested at the doses of 0, 250, 500 and 1000 mg/kgp.o. once daily for 28 days revealed decreases in the body weightand water consumption, and increases in food consumptionwithout any significant difference in the relative organ weight inmice (Mbianctha et al., 2013). The serum and hepatic level of ALTincreased significantly, but that was not the case in the levels ofAST, proteins and creatinine in all the treated animals comparedwith the animals of the group controls. Also, the aqueous extract ofA. vogelii showed reno-protective and hepatoprotective effect ascompared with the control following ethanol-induced toxicity inrats (Ayoka et al., 2014).

Ogbonnia et al. (2011) reported the evaluation of the acute andsubacute toxicities of a Nigerian polyherbal tea remedy, preparedwith A. vogelii, Ficus exasperata and Viscum album in Swiss albinomice and wistar rats of both sexes. The acute toxicity (LD50) of thepolyherbal tea was determined to be 8.970 g/kg p.o in mice. Thetea significantly reduced plasma glucose, LDL-cholesterol, AST andcreatinine levels, but increased HDL-cholesterol with no sig-nificant increase in the body weight and ALT levels. The subacutetoxicity of the aqueous extract of A. schweinfurthii bark at doses250 mg/kg, 500 mg/kg and 1000 mg/kg showed no significantvariation in the evaluated parameters on male and female rats for28 days (Christophe et al., 2015).

The cytotoxic activity of the crude methanol extracts obtainedfrom the stem, roots and leaves of A. djalonensis and three naturalplant constituents (djalonenol, sweroside (1) and djalonensone(27) respectively) isolated from these extracts were evaluated invitro against ST-57 brain tumor transformed fibroblasts (Onochaet al., 2003). Comparatively, the three crude extracts as well asdjalonenol and sweroside (1) exhibited low cytotoxicity (ED50 40–70 μg/mL) while djalonensone (27) was not significantly cytotoxicagainst the brain tumor transformed fibroblasts (Onocha et al.,2003). The ethanol extracts of A. grandiflora showed little to notoxicity to brine shrimps (Mosh et al., 2010). Similar, the activity ofA. djalonensis on brine shrimps lethality was not significant(Awachie and Ugwu, 1997).

The effect of aqueous ethanol extract of A. vogelii leaves againstCCl4 induced toxicity in wistar albino rats restored the liverfunction to near normal indicating the protection of hepatic cells,also the extract increased the rate of erythropoiesis and anti-oxidant activity (Iroanya et al., 2015). The extract showed dosedependent significant increase in the levels of catalase, glutathioneperoxidase, superoxide dismutase, reduced glutathione and glu-tathione-S-transferase with decrease in the level of MDA com-pared to the normal and toxin control groups. The administration

of 800 mg/kg of extract reduced the levels of ALP, AST and ALTlevels almost the same as Silymarin. Also, the extract stimulatedsignificant (po0.05) increase in PCV, Hb, platelet and MCH levelscompared to the toxin control group.

The oral administration of 67 mg/kg of defatted ethanol rootbark extract of A. nobilis reduced pentobarbitone-induced sleep inCCl4-poisoned mice, and effect was comparable to that of Silibinin(Madubunyi and Asuzu, 1996). Elevation of serum ALT and ASTinduced by CCl4 intoxication in rats were also significantly atte-nuated by the defatted ethanol root bark extract of A. nobilis(Madubunyi and Asuzu, 1996). Overall, the Anthocleista species aresafe and not toxic at considerably high doses. The toxicity studiesrevealed that the genus possess hepatoprotective, reno-protective,free radical scavenging, and antioxidant properties. The abovefindings imply and validate the safety and tolerability of the plantvarious extracts in animals models. The 41 g/kg LD50 impliesdrug safety and tolerability in animal models. Additionally, sub-acute toxicity studies have shown safety and tolerability attribu-table partly to the hepatoprotective and antioxidant effects of theplant. The subacute toxicity studies have shown considerablesafety and tolerability on over all parameters of health and implysafe usage, as practiced and experienced folklorically.

7. Conclusion

Six of the fourteen accepted species of Anthocleista have beenreported for their traditional medicinal uses in Africa. Scientificstudies on Anthocleista have given credence to their use by tradi-tional healers or locals in the treatment/management of variousailments such as diabetes, pain, inflammations, wounds, malaria,hypertension, stomach disorders, infertility, obesity, typhoid andworm infestations. However, its use as a contraceptive, antidotefor snake bite, ear and eye treatments or in the treatment ofasthma, STDs, jaundice, hemorrhoid, hernia, cancer, etc. had notbeen scientifically researched or proven.

Forty chemical compounds were shown to have been isolatedbelonging to the groups of secoiridoids, nor-secoiridoids, xan-thones, phytosterols, triterpenes, alkaloids, and others. The che-mical structures of 29 isolated chemical compounds were dis-played. Majority of the studies on Anthocleista species were oncrude extract, few on fractions and very few on isolated com-pounds. There were no reports of mechanisms of action of theextracts/fractions/compounds of these plants on any of the diseaseconditions indicating that most of the studies were basic or pre-liminary and no clinical trial studies were found. Generally, theplants of this genus are considered to be safe and non-toxic aspracticed and believed folklorically even at higher concentrationsand subsequently validated in experimental animals.

This review has provided for the first time a repository ofethnopharmacological information while critically evaluating therelation between the traditional medicinal uses, chemical con-stituents and pharmacological activities of the Anthocleista species.Therefore, researchers have to move quickly and deeply in theinvestigations of this species, particularly for antidiabetic and an-timicrobial agents. Also, there is need for substantial advancedresearch on their chemistry and pharmacological properties (bothin vivo and in vitro), the determination of the mode of action of theactive principles for new and already known pharmacological ac-tivities and commencement of clinical studies of some Anthocleistaspecies which will hopefully lead to newer, more effective and lesstoxic drugs.


Acknowledgments

We wish to thank The World Academy of Sciences (TWAS) andCOMSATS Institute of Information Technology (CIIT) for giving thelead author the Award of 2014 CIIT-TWAS Sandwich PostgraduateFellowship in CIIT, Abbottabad, Pakistan. Thanks to Dr. EthelbertChukwuagozie and Dr. Opeolu Ojo who assisted in sourcing somematerials for the writing of this paper.

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