Vernonia amygdalina Delile

Last updated: 01 September 2016

Scientific Name

Vernonia amygdalina Delile  

Synonyms

Bracheilema paniculatum R.Br., Cacalia amygdalina Kuntze, Cheliusia abyssinica Sch.Bip. ex A.Rich., Decaneurum amygdalinum DC., Vernonia adenosticta Fenzl ex Walp., Vernonia eritreana Klatt, Vernonia giorgii De Wild., Vernonia randii S.Moore, Vernonia vogeliana Benth., Vernonia weisseana Muschl. [1]

Vernacular Name

English Bitterleaf, common bitterleaf [2]
Kenya Olusia [3]
Nigeria Burzu, ewuro, ewuro gidi, ewuro jije, ewuro-oko, ewuroaja, olubo, olugbu, orikhue, orin, pako, sabulum-mata, shiwak, shiwaka, uha [3]
Southern Africa Monqo (Yei), sikakadzi, sikavakadzi (Shona) [3]
Tanzania Ekiluluza, mtugutu, omubilizi [3]
Uganda Omubilizi, umubilizi, umuyobora [3]
West Africa Bata liffi, bittas, e-bita lif [3]
France Vernonie, Vernonie commune, ndole [2]
Portugal Sucumdiera, pau fede [2].

Geographical Distributions

No documentation.

Botanical Description

Vernonia amygdalina is a member of the Asteraceae family. It is a shrub or small tree that can reach up to 10 m high with trunk diameter reaching up to 40 cm. The bark is grey to brown, smooth, becoming fissured and when young is densely pubescent. [2]

The leaves are alternate, simple, with petiole measuring 0.2-4 cm long. The leaf blade is ovate-elliptical to lanceolate and measures 4-15 cm x 1-4 cm, cuneate or rounded at base, shortly acuminated at the apex, margin minutely toothed to coarsely serrate, finely pubescent but often glabrescent. The inflorescence is in the form of a head, arranged in terminal, compound, umbel-like cymes. Head stalk is measure about 1 cm long, pubescent. [2]

The flowers are bisexyal, regular, 5-merous, strongly exserted from the involucres which are cylindrical to broadly ellipsoid.[2]

The fruit is a 10-ribbed achene measuring 1.5-3.5 mm long, pubescent and glandular, brawn to black, crowned by a much longer pappus bristles. [2]

Cultivation

No documentation.

Chemical Constituent

V. amygdalina  has been reported to contain vernodaline, vernomygdin, vernodalol, vernolide, hydroxyvernolide, tannins, vitamin C, luteolin, luteolin 7-O-β-glucoronide, leteolin 7-O-β-glucoside, vernonioside D and E, vernolepin, vernonioside A1-A4, vernonioside B1-B3, vernodalinol, α-muurolol, 1,5-dicaffeoyl-quinic acid, dicaffeoyl-quinic acid, chlorogenic acid and luteolin-7-O-glucoside. [4][5][6][7][8][9][10]

Plant Part Used

Leaves, barks and seeds. [4]

Traditional Use

V. amygdalina  had been introduced into the Malaysian herbal armamet and there has been quite a good followings on the use of the plant to treat diabetes, hypertension and hypercholesterolaemia. The plant is a vegetable in its native land and is put through a detoxification process before being cooked as food. The process involved boiling the leaves several times with change of water after each cycle until the bitterness disappears. [2][4]

The leaves are used on wounds as a substitute for iodine in Nigeria. The leaves are also used to treat fevers especially malaria, hepatitis, and skin parasitic infestations like scabies. The decoction of the V. amygdalina  leaves is prescribed for cough, as a laxative and as a fertility inducer. It is also used to treat headache. [2]

In West Africa the decoction of the V. amygdalina  leaves or bark is used in the treatment of diarrhea, dysentery and other gastrointestinal disorders. It is commonly used as a vermifuge not only by humans bit also chimpanzee. The young branches are chewed on to clean and strengthen teeth and clears gum infection. It also acts as an appetite stimulant and a tonic. [2][4]

The V. amygdalina  root infusion are used to treat sexually transmitted diseases while that of the bark clears fever. The cold water extract of the roots together with leaves of Vigna sinensis is a traditional remedy for schistosomiasis [2][4]. The infusion of the roots is used as a douche for uterine pain [11].

Preclinical Data

Pharmacology

Antiplatelet activity

Vernolepin is a sesquiterpene lactone isolated from the dried fruit of V. amygdalina. It was found to have antiaggregating and diaggregating activity against rabbit platelet aggregation induced by arachindonic acid or ADP without inhibition of cyclo-oxygenase or lipoxygenase. Electronmicroscopy showed that the drug protects platelets against adhesion and desegregation effects. [7][8]

Antisickling activity

Methanol extract of V. amygdalina leaf exhibited significant antisickling activity but not as good as those of Solenostemon monostachyus, Carica papaya seed oil and Ipomoea involucratan in males with sickle-cell anaemia. The effects observed include a lowering of levels of sickle blood cells, reduction in Fe2+/Fe3+ ratio, increased in haemoglobin concentration, and inhibition of sickle cell polymerization. [12]

Antihaemolytic activity

Methanol extract of V. amygdalina was seen to be able to reduce tert-butyl hydropreoxide (t-BHP)-induced eryhtocyte lysis significantly. The effective dose range is between 25-150 μg/L. This protective effects seem to be related to the antioxidant activity of the extract. On the contrary, it has been found that infusion of the leaves induces haemolysis of mammalian erythrocyte in vitro, with Human genotype-SS (1024) having the highest susceptibility. Human genotype-AS were moderately affected while Human genotype-AA (256) were highly resistant. [13][14]

Antiallergic activity

Aqueous and methanol extracts of the leaves of V. amygdalina showed anti-allergic activity as a prophylactic and as curative. In the prophylactic protocol both extracts exerted significant inhibitory effects on the development of Atopic Dermatitis symptoms, the production of IgE, TNF-alpha, IL-5 and IFN-gamma and on the increase thickness of ear. In the curative protocol, it was found that topical application of both extracts markedly improved the skin lesions i.e. erythema/haemorrhage, scaling/dryness, erosion/excoriation and decrease ear thickness in mice. There were also decreases in serum total IgE, MCP-1 and eotaxin. The methanol extract was found to improved chronic eczema dermatitis skin symptoms in a patient. [15]

Myometrial contractility

Nine plants were screened for the myometrial contractile activity and included in this study was the leaves of V. amygdalina. It was found that the aqueous extract of V. amygdalina induced significant sustained increases in human myometrial smooth muscle contractility. [16]

Anticancer activity

Many studies had been conducted to determine the effects of V. amygdalina on the activity of cancer cells in particular the human breast cancer and prostatic cancer. It was found that V. amygdalina was able to inhibit the growth of MCF-7 cells in a dose dependent manner upon exposure for 48 hours. There was a slight increase in DNA damage seen in the form of slight increase in comet tail-length, tail arm and tail moment and percentage in DNA cleavage at all tested doses. This indicate that the plant induced minimal genotoxic damage in MCF-7 cells. Similar effects were seen in BT-549 i.e. cell growth inhibition and DNA synthesis inhibition. The plant also exhibited chemopreventive activity attributed to its ability to scavenge free radicals, induce detoxification, inhibit stress response proteins and interfere with DNA binding activity of some transcription factors. Vernodalinol, a sesquiterpene lactone, isolated from the leaves of V. amygdalina effectively inhibited breast cancerous cell growth at a dose of 25-50 μg/mL. The LC50 being 70-75 μg/mL in MCR-7 cells. [9][17][18][19][20][21]

Androgen-independent PC-3 cells are sensitive to V. amygdalina treatment in vitro. This qualifies the plants as a candidate agent for the treatment of Paclitaxel-resistant prostatic cancer. The sensitivity of TAX-resistant to V. amygdalina is probably due to the differential regulatory patterns of MAPK, c-Myc, AKT, and p-gp activities/expressions. [22]

Irradiation protection activity

Methanol extract of V. amygdalina leaves exhibited antioxidant activity. Antioxidant is known to mitigate radiation damage in tissues. Rat pretreated with methanol extract of V. amygdalina were subjected to irradiation to their heads. At autopsy it was found that the tested group of rats did not show the effects of gamma irradiation i.e. reduction of relative weight of whole brain, relative weight of the cerebellum, the maximum width, rosrocaudal dimension and dorsoventral extent of the cerebellum. [23]

Induction of hyperacidity and increase intestinal motility

Aqueous extract of V. amygdalina when infused intragastrically caused a significant increase in acid production in rats. This was reduced by ranitidine or atropine. The extract also evoked contraction of isolated guinea pig ileum which was inhibited by atropine. [24]

Hypolipidaemic activity

Aqueous extract of V. amygdalina leaves showed hypolipidaemic and antioxidant activity in streptozotosin induced diabetic rats. This is evidenced by the fact that the extract was able to reduce malondialdehyde levels, significantly reduce triglyceride levels and normalized cholesterol concentration. Methanol extract of V. amygdalina leaves also exhibited lipid-lowering effects in hypercholesterolaemic and also diabetic rats. The plasma and post mitochondrial fraction cholesterol and LDL-cholestrol levels were observed to have reduced following administration of 100 mg/kg and 200 mg/kg dose of the extract. There was a corresponding increase in HDL-cholesterol and an augmentation of cholesterol-induced decrease in PMF glutathiones levels. The extracts also decrease significantly lipid peroxidation. These were observed in hypercholestrolaemic rats but not in normal rats. [25][26]

Antihypertensive activity

In a survey on the use of complementary and alternative medicine amongst 225 hypertensive patients in Nigeria, it was found that 9.1% used V. amygdalina together with their antihypertensive therapy. The polyphenolic fraction (cholorophyllic fraction) of the leaf extract of V. amygdalina displayed high potency against angiotensin converting enzyme (ACE) and rennin. This provide some rationale in the use of the plant in the treatment of hypertension. [27][28]

Antidiabetic activity

V. amygdalina leaves had been used in the treatment of diabetes in African countries with reasonable success. Most used the leaves in combination with conventional antidiabetic therapy. In a study to evaluate the antidiabetic activity of the leaves of V. amygdalilna it was found that the ethanol extract could improve the glucose tolerance test in STZ-induced diabetic rats. The following were also observed: a) decrease in fasting blood glucose level; b) protection of pancreatic beta-cells against STZ-induced damage and c) decrease triglyceride and total cholesterol level. There is evidence that it may stimulate skeletal muscle’s glucose uptake since there were increase in expression of GLUT 4 in diabetic rat skeletal muscles and also increase in GLUT 4 tanslocation to plasma membrane thus its ability to restore skeletal muscle glycogenesis. At the same time the extract inhibited hepatic gluconeogenesis by inhibiting glucose-6-phosphatase. A study of the antidiabetic effects of combining V. amygdalina with Azadirachta indica was done and it was found that in combination the hypoglycaemic effects were rapid and a reversal of hepatic and pancreatic histology was observed. This synergy was believed to be exerted by oxidative stress attenuation, insulin mimetic action and beta-cell regeneration. [29][30][31][32]

Hepatoprotective activity

V. amygdalina leaves possess hepatoprotective activity against a number of liver toxins i.e. carbon tetrachloride, acetaminophen and even irradiation. The presence of sesquiterpene lactones in the leaves had been suggested as being responsible for the activity. Administration of various extracts (aqueous/ethanol) prior to induction of liver injury by the mentioned poisons had succeeded in prevention of the occurrence of the damage. This was evidenced by a significant reduction in activities of ALT, AST and OCT and also histologically in animals pretreated with the extracts. There was evidence to suggest this protective activity is mediated through the antioxidant activity in the leaf extracts. [33][34][35][36][37]

Antimicrobial activities

Antiparasitic

The chloroform and methanol extracts of V. amygdalina showed anti-leishmanial activity. The amstigotes appears to be more sensitive to the extracts than the promastigotes. Between the two extracts, the chloroform extracts had stronger parasitical activity against Leishmania aethiopica with ED50 of 74.4 μg/mL. In the case of Leishmania major the methanol extract was found to be the most potent compared to aqueous and hexane extracts of the leaves. There were high suppression of infectivity and viability of intracellular amastigotes at levels lower than that which elicited cytotoxicity in macrophages. Infected mice treated with the methanol extract showed delayed onset of the disease with a significant reduction in lesion size and attenuation of the histopathological outcome characterized by intact epidermis and less tissue destruction in skin, spleen and liver. [38][39]

In a survey on the use of plants in the treatment of malaria in Uganda, V. amygdalina seem to be frequently mentioned. In a screening of seven medicinal plant ethanol extracts and twenty fractions from the partition of initial ethanol extracts, the ethanol extract of V. amygdalina leaves showed antimalarial activity (5<IC50 < 10 μg/mL) while the petroleum ether fraction showed more pronounced antiplasmodial activity (IC50< 3 μg/mL). The extracts of the leaves and root bark showed significant antiplasmodial activity. Prophylactic use of V. amygdalina extract in combination with chloroquin proved to be more effective against P. berghei in infected mice as compared to chloroquin alone. In this case it was observed that there were a) shortened parasite clearance time; b) prolonged recrudescent time; and c) improved day 14 cure rate. In a clinical trial to assess the efficacy and safety of the infusion of fresh V. amygdalina leaves for the treatment of uncomplicated malaria in patients 12 years and above, the investigators found no evidence of significant side-effects or toxicity from the use of the medication. The adequate clinical response (ACR) at day 14 was 67% and complete parasite clearance was 32% of the ACR and of these recrudescence occurred in 71%. [40][41][42][43][44][45][46][47]

Antifungal 

Two sesquiterpene lactones (vernolide and vernodalol) isolated from the leaves of V. amygdalina exhibited differing antifungal activities. In the case of vernolide the activity was high against Penicillium notatu (LD50 = 0.2 mg/mL), Aspergillus flavus and Aspergillus niger (LD50 = 0.3 mg/mL) and Mucor hiemalis (LD50 = 0.4 mg/mL), while vernodalol showed moderate inhibition against Aspergillus flavus (LD50 = 0.3 mg/mL), Penicillium notatum (LD50 = 0.4 mg/mL) and Aspergillus niger (LD50 = 0.5 mg/mL). [48]

Antibacterial

Methanol extract of V. amygdalina leaf did not show significant antibacterial activity being only effective against S. aureus but not against P. aeruginosa. The two sesquiterpene lactone (vernolide and vernodalol) isolated from the leaves were found to be effective against gram positive bacteria but not the gram negative ones. [48][49][50]

Toxicity

No documentation.

Clinical Data

Clinical findings

No documentation.

Precautions

No documentation.

Side effects

No documentation.

Pregnancy/Breast Feeding

Aqueous extract of the V. amgydalina leaves can induced significant myometrial contraction. While this may be useful during the conduct of labours to assist delivery, its use for whatever reason during pregnancy should be contraindicated for fear of leading to abortion. [16]

Age limitation

No documentation.

Adverse reaction

Some of the constituents must be regarded as being toxic, and little in known of their effects in humans, In West Africa, V. amygdalina is widely used as a vegetable. It is preprocessed before being consumed to remove the bitterness (toxic elements). The preprocess varies form country to country from repeated boiling and decanting the water to remove the bitter principle to soaking in water to be left to stand before being cooked, a process that removes the bitter taste and presumably reduces the toxic effects of the sesquiterpenes. [2][4]

Interaction & Depletion

No documentation.

Interaction with drug

It has been found that co-administration of V. amygdalina and digoxin increases the absorption of the latter. This is due to the fact that V. amygdalina inhibit p-gp (permeability glycoprotein) and modulating the pharmacokinetic disposition of other p-gp substrate drug. Patients on digoxin should exercise extra caution when taking V. amygdalina leaves either as vegetable or as an alternative/complimentary medication. [51][52]

There is a risk of potentiation of anticoagulant activity in patients on anticoagulant therapy. There is a possible additive effect on lipid-lowering drug and antihypertensive drugs when used together in therapy. Patients on medications should consult or inform their physicians of their use of the plant as adjuvant to therapy [6][7][25][26]. It would be wise for diabetics on antidiabetic therapy to inform their physician when they are taking the leaves of V. amygdalina. There would eventually arise the need to modify the antidiabetic therapy to suite the probable changes in glycaemic control [29][30][31][32].

Interaction with other Herbs

No documentation.

Contraindications

No documentation.

Dosage

No documentation.

Poisonous Management

No documentation.

Line drawing

No documentation.

References

  1. The Plant List. Ver1.1. Vernonia amygdalina Delile [homepage on the Internet]. c2013 [updated 2012 Feb 11; cited 2016 Aug 10]. Available from: http://www.theplantlist.org/tpl1.1/record/gcc-2949
  2. Fomum FU. Vernonia amygdalina Delila. In: Grubben GJH, Denton OA. Plant Resources of Tropical Africa 2. Vegetables. Wageningen, Netherlands: PROTA Foundation/Backhuys Publishers/CTA, 2004; p. 543-544.
  3. Quattrocchi U. CRC world dictionary of medicinal and poisonous plants: Common names, scientific names, eponyms, synonyms, and etymology. Volume V R-Z. Boca Raton, Florida: CRC Press, 2012; p. 721.
  4. Mueller MS, Mechler E. Medicinal plants in Tropical countries: Traditional use, experience, facts. Stuttgart: Geroge Thieme Verlag, 2005; p. 147-148.
  5. Kupchan SM, Hemingway RJ, Karim A, Werner D. Tumor inhibitors. XLVII. Vernodalin and vernomygdin, two new cytotoxic sesquiterpene lactones from Vernonia amygdalina Del. J Org Chem. 1969;34(12):3908-3911.
  6. Laekeman GM, Mertens J, Totté J, Bult H, Vlietinck AJ, Herman AG. Isolation and pharmacological characterization of vernolepin. J Nat Prod. 1983;46(2):161-169.
  7. Laekeman GM, De Clerck F, Vlietinck AJ, Herman AG. Vernolepin: An antiplatelet compound of natural origin. Naunyn Schmiedebergs Arch Pharmacol. 1985;331(1):108-113.
  8. Koshimizu K, Ohigashi H, Huffman MA. Use of Vernonia amygdalina by wild chimpanzee: possible roles of its bitter and related constituents. Physiol Behav. 1994;56(6):1209-1216.
  9. Luo X, Jiang Y, Fronczek FR, Lin C, Izevbigie EB, Lee KS. Isolation and structure determination of a sesquiterpene lactone (vernodalinol) from Vernonia amygdalina extracts. Pharm Biol. 2011;49(5):464-70.
  10. Ogunbinu AO, Flamini G, Cioni PL, Ogunwande IA, Okeniyi SO. Essential oil constituents of Eclipta prostrata (L.) L. and Vernonia amygdalina Delile. Nat Prod Commun. 2009;4(3):421-424.
  11. Schmidt E, Lotter M, McCleland W. Trees and shrubs of Mpumalanga and Kruger National Park. Johannesburg: Jacana Media. 2002; p. 672.
  12. Afolabi IS, Osikoya IO, Fajimi OD, et al. Solenostemon monostachyus, Ipomoea involucrata and Carica papaya seed oil versus Glutathione, or Vernonia amygdalina: Methanolic extracts of novel plants for the management of sickle cell anemia disease. BMC Complement Altern Med. 2012;12:262.
  13. Adesanoye OA, Molehin OR, Delima AA, Adefegha AS, Farombi EO. Modulatory effect of methanolic extract of Vernonia amygdalina (MEVA) on tert-butyl hydroperoxide-induced erythrocyte haemolysis. Cell Biochem Funct. 2013;31(7):545-550.
  14. Oboh G. Nutritive value and haemolytic properties (in vitro) of the leaves of Vernonia amygdalina on human erythrocyte. Nutr Health. 2006;18(2):151-60.
  15. Ngatu NR, Okajima MK, Yokogawa M, Hirota R, Takaishi M, Eitoku M, Muzembo BA, Sabah AB, Saruta T, Miyamura M, Kaneko T, Sano S, Suganuma N. Anti-allergic effects of Vernonia amygdalina leaf extracts in hapten-induced atopic dermatitis-like disease in mice. Allergol Int. 2012;61(4):597-607.
  16. Attah AF, O'Brien M, Koehbach J, Sonibare MA, Moody JO, Smith TJ, Gruber CW. Uterine contractility of plants used to facilitate childbirth in Nigerian ethnomedicine. J Ethnopharmacol. 2012;143(1):377-382.
  17. Yedjou C, Izevbigie E, Tchounwou P. Preclinical assessment of Vernonia amygdalina leaf extracts as DNA damaging anti-cancer agent in the management of breast cancer. Int J Environ Res Public Health. 2008;5(5):337-341.
  18. Gresham LJ, Ross J, Izevbigie EB. Vernonia amygdalina: anticancer activity, authentication, and adulteration detection. Int J Environ Res Public Health. 2008;5(5):342-348.
  19. Oyugi DA, Luo X, Lee KS, Hill B, Izevbigie EB. Activity markers of the anti-breast carcinoma cell growth fractions of Vernonia amygdalina extracts. Exp Biol Med (Maywood). 2009;234(4):410-417.
  20. Luo X, Oyugi DA, Lin C, Izevbigie EB, Lee KS. Isolation and characterization of the antibreast carcinoma cell growth components of Vernonia amygdalina extracts. Exp Biol Med (Maywood). 2010;235(12):1472-1478.
  21. Farombi EO, Owoeye O. Antioxidative and chemopreventive properties of Vernonia amygdalina and Garcinia biflavonoid. Int J Environ Res Public Health. 2011;8(6):2533-2555.
  22. Cameron KS, Howard CB, Izevbigie EB, Hill BJ, Tchounwou PB. Sensitivity and mechanisms of taxol-resistant prostate adenocarcinoma cells to Vernonia amygdalina extract. Exp Toxicol Pathol. 2012. pii: S0940-2993(12)00108-X.
  23. Owoeye O, Farombi EO, Onwuka SK. Gross morphometric reduction of rats' cerebellum by gamma irradiation was mitigated by pretreatment with Vernonia amygdalina leaf extract. Rom J Morphol Embryol. 2011;52(1):81-88.
  24. Owu DU, Ben EE, Antai AB, Ekpe EA, Udia PM. Stimulation of gastric acid secretion and intestinal motility by Vernonia amygdalina extract. Fitoterapia. 2008;79(2):97-100.
  25. Nwanjo HU. Efficacy of aqueous leaf extract of Vernonia amygdalina on plasma lipoprotein and oxidative status in diabetic rat models. Niger J Physiol Sci. 2005;20(1-2):39-42.
  26. Adaramoye OA, Akintayo O, Achem J, Fafunso MA. Lipid-lowering effects of methanolic extract of Vernonia amygdalina leaves in rats fed on high cholesterol diet. Vasc Health Risk Manag. 2008;4(1):235-41.
  27. Amira OC, Okubadejo NU. Frequency of complementary and alternative medicine utilization in hypertensive patients attending an urban tertiary care centre in Nigeria. BMC Complement Altern Med. 2007;7:30.
  28. Ajibola CF, Eleyinmi AF, Aluko RE. Kinetics of the inhibition of renin and angiotensin i converting enzyme by polar and non-polar polyphenolic extracts of Vernonia amygdalina and Gongronema latifolium leaves. Plant Foods Hum Nutr. 2011;66(4):320-327.
  29. Gbolade AA. Inventory of antidiabetic plants in selected districts of Lagos State, Nigeria. J Ethnopharmacol. 2009;121(1):135-139.
  30. Ogbera AO, Dada O, Adeyeye F, Jewo PI. Complementary and alternative medicine use in diabetes mellitus. West Afr J Med. 2010;29(3):158-162.
  31. Ong KW, Hsu A, Song L, Huang D, Tan BK. Polyphenols-rich Vernonia amygdalina shows anti-diabetic effects in streptozotocin-induced diabetic rats. J Ethnopharmacol. 2011;133(2):598-607.
  32. Atangwho IJ, Ebong PE, Eyong EU, Asmawi MZ, Ahmad M. Synergistic antidiabetic activity of Vernonia amygdalina and Azadirachta indica: biochemical effects and possible mechanism. J Ethnopharmacol. 2012;141(3):878-887.
  33. Babalola OO, Anetor JI, Adeniyi FA. Amelioration of carbon tetrachloride-induced hepatotoxicity by terpenoid extract from leaves of Vernonia amydgalina. Afr J Med Med Sci. 2001;30(1-2):91-93.
  34. Iwalokun BA, Efedede BU, Alabi-Sofunde JA, Oduala T, Magbagbeola OA, Akinwande AI. Hepatoprotective and antioxidant activities of Vernonia amygdalina on acetaminophen-induced hepatic damage in mice. J Med Food. 2006 Winter;9(4):524-530.
  35. Adaramoye O, Ogungbenro B, Anyaegbu O, Fafunso M. Protective effects of extracts of Vernonia amygdalina, Hibiscus sabdariffa and vitamin C against radiation-induced liver damage in rats. J Radiat Res. 2008;49(2):123-131.
  36. Adesanoye OA, Farombi EO. Hepatoprotective effects of Vernonia amygdalina (astereaceae) in rats treated with carbon tetrachloride. Exp Toxicol Pathol. 2010;62(2):197-206.
  37. Akinola OB, Omotoso GO, Akinola OS, Dosumu OO, Adewoye ET. Effects of combined leaf extract of Vernonia amygdalina and Azadirachta indica on hepatic morphology and hepatotoxicity markers in streptozotocin-induced diabetic rats. Zhong Xi Yi Jie He Xue Bao. 2011;9(12):1373-1379.
  38. Tadesse A, Gebre-Hiwot A, Asres K, Djote M, Frommel D. The in vitro activity of Vernonia amygdalina on Leishmania aethiopica. Ethiop Med J. 1993 Jul;31(3):183-189.
  39. Alawa JN, Carter KC, Nok AJ, Kwanashie HO, Adebisi SS, Alawa CB, Clements CJ. Infectivity of macrophages and the histopathology of cutaneous lesions, liver and spleen is attenuated by leaf extract of Vernonia amygdalina in Leishmania major infected BALB/c mice. J Complement Integr Med. 2012;9:Article 10.
  40. Tabuti JR. Herbal medicines used in the treatment of malaria in Budiope county, Uganda. J Ethnopharmacol. 2008;116(1):33-42.
  41. Abosi AO, Raseroka BH. In vivo antimalarial activity of Vernonia amygdalina. Br J Biomed Sci. 2003;60(2):89-91.
  42. Tona L, Cimanga RK, Mesia K, Musuamba CT, De Bruyne T, Apers S, Hernans N, Van Miert S, Pieters L, Totté J, Vlietinck AJ. In vitro antiplasmodial activity of extracts and fractions from seven medicinal plants used in the Democratic Republic of Congo. J Ethnopharmacol. 2004;93(1):27-32.
  43. Njan AA, Adzu B, Agaba AG, Byarugaba D, Díaz-Llera S, Bangsberg DR. The analgesic and antiplasmodial activities and toxicology of Vernonia amygdalina. J Med Food. 2008;11(3):574-581.
  44. Iwalokun BA. Enhanced antimalarial effects of chloroquine by aqueous Vernonia amygdalina leaf extract in mice infected with chloroquine resistant and sensitive Plasmodium berghei strains. Afr Health Sci. 2008;8(1):25-35.
  45. Challand S, Willcox M. A clinical trial of the traditional medicine Vernonia amygdalina in the treatment of uncomplicated malaria. J Altern Complement Med. 2009;15(11):1231-1237.
  46. Stangeland T, Alele PE, Katuura E, Lye KA. Plants used to treat malaria in Nyakayojo sub-county, western Uganda. J Ethnopharmacol. 2011;137(1):154-166.
  47. Zofou D, Tene M, Ngemenya MN, Tane P, Titanji VP. In vitro antiplasmodial activity and cytotoxicity of extracts of selected medicinal plants used by traditional healers of Western cameroon. Malar Res Treat. 2011;2011:561342.
  48. Erasto P, Grierson DS, Afolayan AJ. Bioactive sesquiterpene lactones from the leaves of Vernonia amygdalina. J Ethnopharmacol. 2006;106(1):117-120.
  49. Okigbo RN, Mmeka EC. Antimicrobial effects of three tropical plant extracts on Staphylococcus aureus, Escherichia coli and Candida albicans. Afr J Tradit Complement Altern Med. 2008;5(3):226-9.
  50. Cheruiyot KR, Olila D, Kateregga J. In-vitro antibacterial activity of selected medicinal plants from Longisa region of Bomet district, Kenya. Afr Health Sci. 2009;9 Suppl 1:S42-6.
  51. Oga EF, Sekine S, Shitara Y, Horie T. P-glycoprotein mediated efflux in Caco-2 cell monolayers: The influence of herbals on digoxin transport. J Ethnopharmacol. 2012;144(3):612-617.
  52. Oga EF, Sekine S, Horie T. Ex vivo and in vivo investigations of the effects of extracts of Vernonia amygdalina, Carica papaya and Tapinanthus sessilifolius on digoxin transport and pharmacokinetics: Assessing the significance on rat intestinal P-glycoprotein efflux. Drug Metab Pharmacokinet. 2013;28(4):314-320.