Phytochemical, Pharmacological, Phyto-cosmeceutical, Toxicity, and In silico Toxicological Evaluations of Vernonia amygdalina Delile – A Review

Abstract

Vernonia amygdalina Delile, which is in the Asteraceae family, is used as food and medicine all over the world, especially in Africa and Asia. This review reports the phytochemical, ethnopharmacological, phyto-cosmeceutical, and toxicological potentials of the plant. Recent scientific exploration of the plant has mainly focused on both its nutritional potential and ethnopharmacological properties. The antioxidant, anti-inflammatory, antidiabetic, hepatoprotective, hematological, anti-plasmodial, antimicrobial, anticancer, neurological, cosmeceutical, and other pharmacological values of V. amygdalina continue to be extensively explored. Many empirical studies of the therapeutic potential of the plant have attributed the ethnomedicinal properties of the plant to its phytochemical constituents, which include glycosides, saponins, tannins, terpenoids, etc. Compounds obtained from the leaves, root, stem, and flowers, which include vemoniosides, vernoamyosides, vernoniamyosides, vernoniosides, vernolide, vernodalol, vernodalin, vernomenin, vernomygdin, vernodalinol, epivernodalol, vernolepin, coumarins, luteolin, edotides, etc. have been identified as bioactive constituents responsible for numerous pharmacological activities of the plant. In addition, the toxicological evaluation of the plant revealed that it is safe for consumption at relatively high concentrations.

Keywords

• Medicinal plant;
• nutraceuticals;
• antidiabetic;
• antioxidant;
• vemoniosides;
• bioactives

References

1. 1. Alara OR, Nour HA, Chinonso IU, and Nassereldeen AK. Extraction and Characteristics of bioactive compounds In Vernonia Amygdalina leaf Ethanoic extract comparing soxhlet and microwave-assisted Extraction techniques. Journal of taibah university for science. 2019; 13 (1): 414-422. Available from:
2. 2. Odangowei IO, Dienize GG and Ngozi GE. Ethnophamacological properties of Vernonia amygdalina (Bitter leaf). Journal of Medicinal Plants Studies. 2019; 7(2): 175-181.
3. 3. Yeap SK, Ho WY, Beh BK, Liang WS, Ky H, Hadi A, Alitheen NB. Vernonia amygdalina Ethnoveterinary an Ethnomedical used Green Vegetable with Multiple Bio-activities. Journal of Medicinal Plants Research. 2010; 4(25): 2787–2812. Available from:
4. 4. Halim A M, Sirajuddin S, Bahar B, Jafar N, Syam A, Masni. The effect of African leaf herbal tea on fast blood glucose on centration of pre-diabetes teachers in Makassar city. Enfermeria Clinica. 2020; 30: 261-264. Available from: .
5. 5. Nwaoguikpe RN. The effect of extract of bitter leaf (Vernonia amygdalina) on blood glucose levels of diabetic rats. International Journal of Biological and Chemical Sciences. 2010. 4(3): 721-729. Available from:
6. 6. Oladunmoye MK, Afolami OI, Oladejo BO, Amoo IA, Osho BI. Identification and Quantification of Bioactive Compounds present in the plant Vernonia amygdalina Delile using GC-MS Technique. Natural products Chemistry and Research. 2019; 7(1): 1-5. Available from: .
7. 7. Atolani O and Olatunji GA: Comprehensive scientific demystification of Kigelia africana: A review. African Journal of Pure and Applied Chemistry. 2009; 3 (9): 158-164. Available from:
8. 8. Islam MT, Hasan J, Hossain-Snigdha HMS, Ali ES, Sharifi-Rad J, Martorell M, Mubarak MS. Chemical profile, traditional uses, and biological activities of Piper chaba Vahl: A review. Journal of Ethnopharmacology. 2020; 257: 1-10. Available from:

9. 9. Habtamu A, Melaku Y. Antibacterial and Antioxidant Compounds from the Flower Extracts of Vernonia amygdalina. Hindawi Advances in Pharmacological sciences. 2018; 2018(4803736): 1-6. Available from:
10. 10. Alara OR, Abdurahman NH, Abdul Mudalip SK, Olalere OA. A Review: Phytochemical and Pharmacological Properties of Vernonia amygdalina. Journal of Chemical Engineering and Industrial Biotechnology. 2017; 2: 80-96. Available from: .
11. 11. Asuzu CU. Bitter herbs of eastern Nigeria (Gongronema latifolium, Vernonia amygalina and vitex doniana). African Journal of Traditional, Complementary and Alternative Medicines. 2018; 15 (3): 47-56. Available from: .
12. 12. Divneet K, Navpreet K, Anuja C. A comprehensive review on phytochemistry and pharmacological activities of Vernonia amygdalina. Journal of pharmacognosy and Phytochemistry. 2019; 8(3): 2629-2636.
13. 13. Kigigha LT, Onyema E. Antibacterial activity of bitter leaf (Vernonia amygdalina) soup on Staphylococcus aureus and Escherichia coli). Sky Journal of Microbiology Research. 2015; 3(4): 41–45.
14. 14. Zaharaddeen NG, Samuel O. The effect of different drying methods on the elemental and nutritional composition of Vernonia amygdalina. Science. 2019; 13(1): 396-401. Available from: .
15. 15. Ogunrinola OO, Fajana OO, Adu OB, Otutuloro AM, Moses TA, Lediju K, Agbabiaka OA, Elemo BO. The effects of Vernonia amygdalina leaves on lipid profile in cadmium-induced rat. MedCrave online Journal of Toxicology. 2019; 5(2): 83-88
16. 16. Zubairu AY, Mukhtar M, Saidu I, Ibrahim Z, Isah S, Garga MA, Kebbi HS. Antibacterial activity of methanolic extract of bitter leaf (Vernonia amygdalina) from various component fractions using column Chromatography. GSC Biological and pharmaceutical sciences. 2019; 7(2): 16-21. Available from: .
17. 17. Olaoluwa JO, Orjiakor PI, Olowe BM, Ukhureigbe OM, Oguntoye DO. Antimicrobial Potentials of Vernonia amygdalina and Honey on Vancomycin-Resistant Staphylococcus aureus. Clinical and Environmental. 2019; 6(5): 1-13. Available from: .
18. 18. Adedapo AA, Aremu OJ and Oyagbemi AA. Antioxidant, Anti-inflammatory and Antinociceptive Properties of the Acetone Leaf Extract of Vernonia amygdalina in Some Laboratory Animals. Advanced Pharmaceutical Bulletin. 2014; 4: 591–598. Available from: .
19. 19. Alara OR, Abdurahman NH, Olalere OA. Ethanolic extraction of flavonoids, phenolics and antioxidants from Vernonia amygdalina leaf using two-level factorial design. Journal of King Saud University – Science. 2020; 32 (1): 7-16. Available from: .
20. 20. Quasie O, Zhang Y, Zhang H, Luo J, Kong L. Four new steroid saponins with highly oxidized side chains from the leaves of Vernonia amygdalina. Phytochemistry letters. 2016; 15: 16-20. Available from: .
21. 21. Luo X, Jiang Y, Fronczek FR, Lin C, Izevbigie EB, Lee S, Lee KS. Isolation and Structure Determination of a Sesquiterpene Lactone (Vernodalinol) from Vernonia amygdalina Extracts. Pharmaceutical Biology. 2011; 49(5): 464–470. Available from: .
22. 22. Oyeyemi IT, Akinlabi AA, Adewumi A, Aleshinloye AO, Oyeyemi OT. A review on Vernonia amygdalina: A folkloric herb with anthelminthic properties. Beni-Suef University Journal of Basic and Applied Sciences. 2018; 7: 43–49. Available from: .
23. 23. Amodu A, Itodo SE, Musa DE. Nigerian Foodstuffs with Tumour Chemosuppressive Polyphenols. International Journal of Pharmaceutical Science Invention. 2013; 2(1): 12–17.
24. 24. Jisaka M, Ohigashi H, Takegawa K, Huffman MA, Koshmizu K. Antinutritional and antimicrobial activities of bitter sesquiterpene lactones of Vernonia amygdalina a possible medicinal plant used by wild chimpanzee. Bioscience, Biotechnology, and Biochemistry. 1993; 57: 833-834. Available from: .
25. 25. Erasto P, Grierson DS, Afolayan AJ. Bioactive sesquiterpene lactones from the leaves of Vernonia amygdalina. Journal of Ethnopharmacology. 2006; 106: 117-120. Available from: .
26. 26. Huffman MA, Gotoh S, Izutsu D, Koshimizu K, Kalunde MS. Further observations on the use of the medicinal plant Vernonia amygdalina (Del.), by a wild chimpanzee, its possible effect on parasite load, and its phytochemistry. African Study Monographs. 1993 14(4):227-240.
27. 27. Osinubi AAA. Effects of Vernonia amygdalina and chlorpropamide on blood glucose. Medical Journal of Islamic World Academic Sciences. 2007; 16: 115-119.
28. 28. Wang J, Song H, Wu X, Zhang S, Gao X, Li F, Zhu X, Chen Q. Steroidal Saponins from Vernonia amygdalina Del. and Their Biological Activity Molecules 2018; 23: 579. Available from: .
29. 29. Erasto P, Grierson DS, Afolayan AJ. Evaluation of Antioxidant Activity and the Fatty Acid Profile of the Leaves of Vernonia amygdalina growing in South Africa. Food Chemistry. 2007a; 104: 636–642. Available from: .
30. 30. Farombi EO and Owoeye O. Antioxidative and Chemopreventive Properties of Vernonia amygdalina and Garcinia biflavonoid. International Journal of Environmental Research and Public Health. 2011; 8: 2533–2555. Available from: .
31. 31. Atangwho IJ, Egbung GE, Ahmad M, Yam MF, Asmawi MZ. Antioxidant versus anti-diabetic properties of leaves from Vernonia amygdalina Del. growing in Malaysia. Food Chem. 2013; 141: 3428–3434. Available from: .
32. 32. Igile GO, Oleszek W, Jurzysta M, Burda S, Fanfunso M, Fasanmade AA. Flavonoids from Vernonia amygdalina and their antioxidant activities. Journal Agriculture for Food Chemicals. 1994; 42: 2445-2448. Available from: .
33. 33. Udensi EA, Ijeh II, Ogbonna U. Effect of traditional processing on the phytochemical and nutrient composition of some local Nigerian leafy vegetables. Journal of Science Technology. 2002; 8: 37-40.
34. 34. Tona L, Cimanga RK, Mesia K, Musuamba CT, De Bruyne T, Apers S, Hermans N, Van Miret S, Pieters L, Totte J, Vlietink AJ. In vitro antiplasmodial activity of extracts and fractions of seven medicinal plants used in the Democratic Republic of Congo. Journal of Ethnopharmacology. 2004; 93: 27-32. Available from: .
35. 35. Dagnon S, Novkova Z, Bojilov D, Nedialkov P, Kouassi C. Development of surrogate standards approach for the determination of polyphenols in Vernonia amygdalina Del. Journal of food composition and analysis. 2019; 82:103231. Available from: .
36. 36. Tsaku AP, Ibrahim T, Ekeleme IK, Nkenne IH, Oti VB, Abimiku RH. Phytochemical and Antibacterial analysis of aqueous and alcoholic extracts of Vernonia amygdalina (del.) Leaf. World journal of Pharmaceutical Research. 2018; 7: 9-17. Available from: .
37. 37. Ayoola GA, Coker HAB, Adesegun SA, Adepoju-Bello AA, Obaweva K, Ezennia EC, Atangbayila TO. Phytochemical screening and antioxidant activities of some selected medicinal plants used for malaria therapy in Southwestern Nigeria. Trop. J. Pharm. Res. 2008; 7:1019-1024. Available from: .
38. 38. Nwanjo HU. Efficacy of aqueous leaf extract of Vernonia amygdalina on plasma lipoprotein and oxidative status in diabetic rat models. Nigeria Journal of Physiological Sciences. 2005; 20: 39-42.
39. 39. Ogundipe OO, Moody JO, Akinyemi TO, Raman A. Hypoglycemic potentials of methanolic extracts of selected plant foods in alloxanized mice. Plant Foods and Human Nutrition. 2003; 58: 1-7.
40. 40. Céspedes CL, Avila JG, Martínez A, Serrato B, Calderón-Mugica JC, Salgado-Garciglia R. Antifungal and Antibacterial Activities of Mexican Tarragon (Tagetes lucida). Journal of Agricultural and Food Chemistry. 2006; 54(10), 3521–3527. Available from: .
41. 41. Izevbigie EB. Discovery of water-soluble anticancer agents (edotides) from a vegetable found in Benin City, Nigeria. Experimental Biology and Medicine. 2003; 228: 293-298. Available from: .
42. 42. Ejiofor II, Das A, Mir SR, Ali M, Zaman K. Novel phytocompounds from Vernonia amygdalina with antimalarial potentials. Pharmacognosy Research. 2020; 12(1): 53-59. Available from:.
43. 43. Ijeh II, Ejike CE. Current perspective on the medicinal potentials of Vernonia amygdalina. Journal of Medicinal Plants Research. 2011; 5(7): 1051-1061. Available from: .
44. 44. Odiongenyi AO, Odoemelam SA, Eddy NO. Corrosion inhibition and adsorption properties of ethanol extract of Vernonia amygdalina for the corrosion of mild steel in H2SO4. Portugaliae Electrochimica Acta. 2009; 27: 33-45.
45. 45. Nduagu C, Ekefan EJ, Nwankiti AO. Effect of some crude plant extracts on growth of Colletotrichum capsici (Synd) Butler and Bisby, causal agent of pepper anthracnose. J. Appl. Biosci. 2008; 6: 184-190.
46. 46. Arhoghro EM, Ekpo KE, Anosike EO, Ibeh GO. Effect of aqueous extract of bitter leaf (Vernonia amygdalina Del) on carbon tetrachloride induced liver damage in albino wistar rats. Eur. J.Sci. Res. 2009; 26: 122-130. Available from: .
47. 47. Salawu SO, Akindahunsi AA. Protective effect of some tropical vegetables against CCl4 – induced hepatic damage. J. Med. Food. 2007; 10: 350-355. Available from: .
48. 48. Fairuz SY, Ismail SI, Farhanah FH, Mahmud TMM. Phytochemical composition in hexane and methanolic leaf extract of Vernonia amygdalina. Malaysian Applied Biology. 2019; 48(5): 11-17.
49. 49. Sinisi A, Munoz E, Abay SM, Habluetzel A, Appendino G, Millan E. Poly electrophilic sesquiterpene lactones from Vernonia amygdalina: new members and differences in their mechanism of thiol trapping and inbioactivity. Journal of Natural Product. 2016; 78(7): 1618–1623. Available from: .
50. 50. Abay SM, Lucantoni L, Dahiya N, Dori G, Dembo EG, Lupidi G. Plasmodium transmission blocking activities of Vernonia amygdalina extracts and isolated compounds. Malaria Journal. 2015; 14: 288. Available from: .
51. 51. Jisaka M, Ohigashi H, Takegawa K, Hirota M, Irie R, Huffman MA, Koshmizu K. Steroid gluccosides from Vernonia amygdalina, a possible chimpanzee medicinal plant. Phytochemistry. 1993; 34: 409-413. Available from:
52. 52. Kupchan SM, Hemingway RJ, Karim A, Werner D. Tumor inhibitors XLVII Vernodalin and vernomygdin, two new cytotoxic sesquiterpene lactones from Vernonia amygdalina Del. Journal of Organic Chemistry. 1969; 34: 3908-3911. Available from: .
53. 53. Ganjian I, Kubo I, Fludzinski P. Insect antifeedant elemanolide lactones from Vernonia amygdalina. Phytochemistry. 1983; 22: 2525-2526. Available from: .
54. 54. Owoeye O, Yousuf S, Akhtar MN, Qamar K, Dar A, Farombi EO, Choudhary MI. Another Anticancer Elemanolide from Vernonia amygdalina Del. International Journal of Biology and Chemical Sciences. 2010; 4: 226–234. Available from: .
55. 55. Laekeman GM, Mertens J, Totte J, Bult H, Vlietinck AJ, Herman AG. Isolation and pharmacological characterization of vernolepin. Journal of Natural Product. 1983; 46: 161-169. Available from:.
56. 56. Laekeman GM, De Clerck F, Vlietinck AJ, Herman AG. Vernolepin: an antiplatelet compound of natural origin. NaunynSchmiedeberg’s Archives Pharmacology. 1985; 331: 108-113. Available from: .
57. 57. Ohigashi H. Toward the chemical ecology of medicinal plant use in chimpanzees: The case of Vernonia amygdalina, a plant used by wild chimpanzees, possibly for parasite-related diseases. Journal of Chemistry Ecology. 1994; 20: 541–553. Available from: .
58. 58. Koshimizu K, Ohigashi H, Huffman MA. Use of Vernonia amygdalina by wild chimpanzee: Possible Roles of Its Bitter and Related Constituents. Physiology and Behavior. 1994; 56(6): 1209-1216. Available from: .
59. 59. Galati G, Teng S, Moridani MY, Chan TS, O’Brien PJ. Cancer chemoprevention and apoptosis mechanisms induced by dietary polyphenolics. Drug Metabolism and Drug Interaction. 2000; 17: 311–349. Available from: .
60. 60. Huffman MA. Self-medicative behavior in the African great apes: an evolutionary perspective into the origins of human traditional medicine. Bioscience. 2001; 51: 651–661. Available from:.
61. 61. Clement E, Erharuyi O, Vincent I, Joy A, Christopher A, et al. Significance of Bitter Leaf (Vernonia amagdalina) In Tropical Diseases and Beyond: A Review. Malarial Chemotherapy Control. 2014; 3(1): 1-10. Available from: .
62. 62. Asawalam EF, Emosairue SO, Hassanali A. Contribution of different constituents to the toxicity of the essential oil constituents of Vernonia amygdalina (compositae) and xylopia aetiopica (annonaceae) on maize weevil, Sitophilus zeamais motschulsky (coleoptera: Curculionidae). African Journal of Biotechnology. 2006; 7(16): 2957-2962.
63. 63. Ogunbinu AO, Flamini G, Cioni PL, Ogunwande IA, Okeniyi, SO. Essential oil constituents of Eclipta prostrata (L.) L. and Vernonia amygdalina delile. Natural Product Communications. 2009; 4(3): 421-424. Available from: .
64. 64. Erasto P, Grierson DS, Afolayan AJ. Antioxidant constituents in Vernonia amygdalina leaves. Pharmaceutical Biology. 2007b; 45(3): 195–199. Available from: .
65. 65. Sonibare OO, Sonibare MA, Adesanya EO. Essential oil composition of Vernonia amygdalina del. from Southwestern Nigeria. Journal of Essential Oil-Bearing Plants. 2009; 12(1): 55-58. Available from: .
66. 66. Okpe O, Habila N, Ikwebe J, Upev VA, Okoduwa SIR, Isaac OT. Antimalarial Potential of Carica papaya and Vernonia amygdalina in Mice Infected with Plasmodium berghei. Journal of Tropical Medicine. art. no. 8738972. 2016;1-6. Available from: .
67. 67. Ajayi EIO, Adeleke MA, Adewumi TY, Adeyemi AA. Antiplasmodial activities of ethanol extracts of Euphorbia hirtawhole plant and Vernonia amygdalina leaves in Plasmodium berghei -infected mice Journal of Taibah University for Science. 2017; 11(6): 831-835. Available from: .
68. 68. Alawa CBI, Adamu AM, Gefu JO, Ajanusi OJ, Abdu PA, Chiezey NP, Alawa JN, Bowman DD. In vitro screening of two Nigerian medicinal plants (Vernonia amygdalina and Annona senegalensis) for anthelmintic activity. Veterinary Parasitology. 2003; 11(1): 73-81. Available from: .
69. 69. Ito N, Fukushima S, Fukushima H. Carcinogenicity and modification of the carcinogenicity response by BHA and BHT and other antioxidants. CRC Crit. Rev. Food Technology. 1985; 15: 109-125. Available from: .
70. 70. Atolani O, Olabiyi ET, Issa AA, Azeez HT, Onoja EG, Ibrahim SO, Zubair MF, Oguntoye OS, Olatunji GA. Green synthesis and characterization of natural antiseptic soaps from the oils of underutilized tropical seed. Sustainable Chemistry and Pharmacy. 2016; 4: 32–39. Available from: .
71. 71. Atolani O, Olatunji GA. Chemical Composition, Antioxidant and Cytotoxicity Potential of Daniellia oliveri (Rolfe) Hutch. & Dalz. Turkish Journal of Pharmaceutical Sciences. 2016; 13(1): 41-46.
72. 72. Atolani O, Olorundare OE, Anoka AN, Osin AO, Biliaminu SA. Antioxidant, Proteinase Inhibitory and Membrane Stabilization Potentials of Moringa oleifera Seed Oil. FABAD Journal of Pharmaceutical Sciences. 2018; 43(2): 1-13.
73. 73. Atolani O, Areh ET, Oguntoye OS, Zubair MF, Fabiyi OA, Oyegoke RA, Tarigha DE, Adamu N, Adeyemi OS, Kambizi L, Olatunji GA. Chemical Characterization, Antioxidant, Cytotoxicity, Anti-Toxoplasma gondii and Antimicrobial Potentials of the Citrus sinensis Seed Oil for Sustainable Cosmeceutical Production. Heliyon. 2020; 6: 2e03399. Available from: .
74. 74. Zubair MF, Atolani O, Ibrahim SO, Oguntoye OS, Abdulrahim HA, Oyegoke, RA, Olatunji, GA. Chemical and biological evaluations of potent antiseptic cosmetic products obtained from Momordica charantia seed oil. Sustainable Chemistry and Pharmacy. 2018; 9: 35–41. Available from: .
75. 75. Zubair MF, Atolani O, Ibrahim SO, Oguntoye OS, Oyegoke RA, Olatunji GA. Fatty acids Composition, Antimicrobial Potential and Cosmeceutical Utilization of Prosopis africana Seed Oil. Journal of Mexican Chemistry Society. 2019; 62(3): 1. Available from: .
76. 76. Torel J, Cillard J, Cillard P. Antioxidant activity of flavonoids and reactivity with peroxy radical. Phytochemistry. 1986; 25: 383-385. .
77. 77. Adaramoye OA, Akintayo O, Achem J, Fafunso MA. Lipid lowering effects of methanolic extracts of Vernonia amygdalina leaves in rats fed on high cholesterol diet. Vascular Health and Risk Management. 2008; 4: 236-241. DOI: .
78. 78. Iwalokun BA, Efedede BU, Alabi-Sofunde JA, Oduala T, Magbagveola OA, Akinwande AI. Hepato-protective and antioxidant activities of Vernonia amygdalina on acetaminophen-induced hepatic damage in mice. Journal of Medicinal Food. 2006; 9(4): 524-530. Available from: .
79. 79. Owolabi MA, Jaja SI, Oyekanmi OO, Olatunji J. Evaluation of the antoxidant activity and lipid peroxidation of the leaves of Vernonia amygdalina. Journal of Complimentary and Integrative Medicine. 2008; 5(1): 21. Available from: .
80. 80. Kambizi L, Bakare-Odunola MT, Oladiji AT, Kola-Mustapha AT, Amusa TO, Atolani O, Njinga NS, Quadri AL. Proteinease inhibition, membrane stabilization, antioxidant and phytochemical evaluations of leaves, seeds and calyces of four selected edible medicinal plants. Cogent Chemistry. 2017; 3: 1314064. Available from: .
81. 81. Da Costa FM, Lemos COT, Arvelos S, Traczynski MR, Da Silva EA, Cardozo-Filho L, Hori CE, Watanabe EO. Evaluation of supercritical carbon dioxide extraction to obtain bioactive compounds from Vernonia amygdalina delile leaves. Chemical Industry and Chemical Engineering Quarterly. 2020; 26(2): 113-124. Available from: .
82. 82. Akah PA, Okafor CL. Blood sugar lowering effect of V. amygdalina del. in an experimental rabbit model. Phytotherapy Resources. 1992; 6: 171-173. Available from: .
83. 83. Gbolade AA. Inventory of antidiabetic plants in selected districts of Lagos State, Nigeria. Journal of Ethnopharmacology. 2009; 121: 135-139. Available from: .
84. 84. Anh HLT, Vinh LB, Lien LT, Cuong PV, Arai M, Ha TP, Lin HN, Dat TTH, Cuong LCV, Kim YH. In vitro study on α-amylase inhibitory and α-glucosidase of a new stigmastane-type steroid saponin from the leaves of Vernonia amygdalina. Natural Product Research. 2019; 35(5): 873-879.
85. 85. Osinubi AAA. Effects of Vernonia amygdalina and chlorpropamide on blood glucose. Medical Journal of Islamic World Academic Sciences. 1996; 16: 115-119.
86. 86. Nwanjo HU, Nwokoro EA. Antidiabetic and biochemical effects of aqueous extract of Vernonia amygdalina leaf in normoglycaemic and diabetic rats Journal of Innovational Life Science. 2004; 7: 6-10.
87. 87. Uhuegbu FO, Ogbuehi KJ. Effect of aqueous extract (crude) of leaves of Vernonia amygdalina (Del.) on blood glucose, serum albumin and cholesterol levels in diabetic albino rats. Global Journal Pure and Applied Science. 2004; 10: 189-194. Available from: .
88. 88. Atangwho IJ, Ebong PE, Egbung GE, Eteng MU, Eyong EU. Effect of Vernonia amygdalina Del. on liver function in alloxan-induced hyper glycemic rats. J. Pharm. Bioresour. 2007a; 4:25–31. Available from: .
89. 89. Atangwho IJ, Ebong PE, Eteng MU, Eyong EU, Obi AU. Effects of Vernonia amygdalina Del. leaf on kidney function of diabetic rats. International Journal of Pharmacology. 2007b; 3:143–148.
90. 90. Atangwho IJ, Ebong PE, Eyong MU, Eteng MU, Uboh FE. Vernonia amygdalina Del.: a potential prophylactic Antidiabetic agent in lipids complication. Global Journal of Pure and Applied Science. 2007c; 13: 103–106.
91. 91. Ekpo A, Eseyin OA, Ikpeme AO, Edoho EJ. Studies on some biochemical effects of Vernonia amygdalina in rats. Asia Journal of Biochemistry. 2007; 2: 193-197. Available from: .
92. 92. Okolie UV, Okeke CE, Oli JM, Ehiemere IO. Hypoglycemic indices of Vernonia amygdalina on post prandial blood glucose concentration of healthy humans. African Journal of Biotechnology. 2008; 7(24): 4581-4585.
93. 93. Atangwho IJ, Ebong PE, Eyong EU, Eteng MU. Combined administration of extracts of Vernonia amygdalina (Del) and Azadirachta indica (A. Juss) mimic insulin in time-course body weight and glucose regulation in diabetic and non-diabetic rats.” Nigerian Journal of Biochemistry and Molecular Biology. 2010; 25:44-49.
94. 94. Okafor GI, Okoli CO, Odo AS, Kelechi NR. Studies on the effect of processing methods on the antihyperglycemic activity of herbal teas from leaves of Vernonia amygdalina Del. Pharmacognosy Research. 2009; 1(5): 256.
95. 95. Erukainure OL, Chukwuma CI, Sanni O, Matsabisa MG, Islam MS. Histochemistry, phenolic content, antioxidant, and anti‐diabetic activities of Vernonia amygdalina leaf extract. Journal of Food Biochemistry. 2018; 43(1): 1-11. Available from: .
96. 96. Cioffi G, Sanogo R, Diallo D, Romussi G, De Tommasi N. New compounds from an extract of Vernonia colorata leaves with anti-inflammatory activity. Journal of Natural Products. 2004; 67: 389–394. Available from: .
97. 97. Liu J, Liu Y, Si Y, Yu S, Qu J, Xu S, Hu Y, Ma S. New vernocuminosides from the stem barks of Vernonia cumingiana Benth. Steroids. 2009; 74: 51–61. Available from: .
98. 98. Eyong EU, Atangwho IJ, David-Oku E, Agiang MA, Ebong PE. Haematological and immunological effect of co- administration of extracts of Vernonia amygdalina and Azadirachta indica on normal and diabetic rats. African Journal of Biotechnology. 2011; 10: 10258–10262. Available from:.
99. 99. Iroanya O, Okpuzor J, Mbagwu H. Anti-nociceptive and anti-phlogistic actions of a polyherbal decoction. International Journal of Pharmacology. 2010; 6(1): 31-36.
100. 100. Koko WS, Mesaik MA, Yousaf S, Galal M, Choudhary MI. In vitro immunomodulating properties of selected Sudanese medicinal plants. Journal of Ethnopharmacology. 2008; 118: 26-34. Available from: .
101. 101. Asante DB, Henneh IT, Acheampong DO, Kyei F, Adokoh CK, Ofori EG, Domey NK, Adakudugu E, Tangella LP, Ameyaw EO. Anti-inflammatory, anti-nociceptive and antipyretic activity of young and old leaves of Vernonia amygdalina. Biomedicine and Pharmacotherapy. 2019; 111: 1187-1203. Available from: .
102. 102. Onasanwo SA, Oyebanjo OT, Ajayi AM, Olubori MA. Anti-nociceptive and antiinflammatory potentials of Vernonia amygdalina leaf extract via reductions of leucocyte migration and lipid peroxidation. Journal of Intercultural Ethnopharmacology. 2017; 6(2): 192-198. Available from: .
103. 103. Wang W, Liao S, Wu Z, Chang C, Wu J. Simultaneous study of antioxidant activity, DNA protection and anti-inflammatory effect of Vernonia amygdalina leaves extracts. PloS One. 2020; 15(7): e0235717. Available from: .
104. 104. Nguyen TXT, Dang DL, Ngo VQ, Trinh TC, Trinh QN, Do TD, Thanh TTT. Anti-inflammatory activity of a new compound from Vernonia amygdalina. Natural Product Research. 2020; 2020(7)1-6. Available from: .
105. 105. Opata MM, Izevbigie EB. Aqueous Vernomia amygdalina extracts alter MCF-7 cell membrane permeability and efflux. International Journal of Environmental Research and Public. 2006. Available from: .
106. 106. Khalafalla MM, Abdellatef E, Daffalla HM, Nassarallah AA, Aboul- Enein KM, Lightfoot DA, Cocchetto A, El-Shemy HA. Antileukemia activity from root cultures of Vernonia amygdalina. Journal of Medicinal Plants Research. 2009; 3(8): 556-562. Available from: .
107. 107. Izevbigie EB, Byrant JL, Walker A. A novel natural inhibitor ofextracellular signal-regulated kinases and human breast cancer cell growth. Experimental Biology and Medicine. 2004; 229: 163-169. Available from: .
108. 108. Howard CB, Izevbigie EB, Opata MM. Inhibition paclitaxel resistant MCF-7Rag cell growth by Vernonia amygdalina extract. 1st AACR Int Conference on Mol. Diagnostics in Cancer Ther. Dev. 2006; 12-15.
109. 109. Yedjou CG, Rogers C, Brown E, Tchounwou PB. Differential effect of ascorbic acid and N-acetyl 1-cysteine on arsenic trioxide mediated oxidative stress in human leukemia (HL-60) cells. Journal of Biochemistry and Molecular Toxicology. 2008; 22: 85-92. Available from: .
110. 110. Gresham LJ, Ross J, Izevbigie EB. Vernonia amygdalina: anticancer activity, authentication and adulteration detection. International Journal ofEnvironmental Research and Public Health. 2008; 5(5): 342-348. Available from: .
111. 111. Oyugi DA, Luo X, Lee KS, Hill B, Izevbigie EB. Activity markers of the anti-breast carcinoma cell growth fractions of Vernonia amygdalina extracts. Experimental Biology and Medicine. 2009; 234(4): 410-417. Available from: .
112. 112. Hasibuan PAZ, Harahap U, Sitorus P, Satria D. The anticancer activities of Vernonia amygdalina Delile. Leaves on 4T1 breast cancer cells through phosphoinositide 3-kinase (PI3K) pathway. Heliyon. 2020; 6(7): e0449. Available from: .
113. 113. Siew YY, Yew HC, Neo SY, Tan CH, Koh HL. Evaluation of anti-proliferative activity of medicinal plants used in Asian Traditional Medicine to treat cancer. Journal of Ethnopharmacology. 2019; 235: 75-87. Available from: .
114. 114. Berman T, Bayati A. What are neurodegenerative diseases and how do they affect the brain? Front Young Minds. 2018; 6:70. Available from: .
115. 115. Ebuehi O, Ajagun-Ogunleye MO. Neurochemical impact of the aqueous extract of Vernonia amygdalina and Talinum triangulare on learning and memory in male Wistar rats. International Journal of Brain and Cognitive Sciences. 2017; 6: 81-88.
116. 116. Ademosun AO, Oboh G, Oyeleye SI, Ejakpovi II, Adewuni TM. Modulation of cholinergic, monoaminergic, and purinergic enzymes of the brain functions by bitter (Vernonia amygdalina) and water bitter (Struchium sparganophora) leaves extracts: comparison of phenolic constituents versus nootropic potentials. Comparative Clinical Pathology. 2017; 26(6): 1267-1272. Available from: .
117. 117. Erukainure OL, Oyebode OA, Ibeji CU, Koorbanally NA, Islam MS. Vernonia Amygdalina Del. stimulated glucose uptake in brain tissues enhances antioxidative activities; and modulates functional chemistry and dysregulated metabolic pathways. Metabolic Brain Disease. 2019; 34(3): 721–732. Available from: .
118. 118. Oboh G, Adedayo BC, Adetola MB, Oyeleye IS, Ogunsuyi OB. Characterization and neuroprotective properties of alkaloid extract of Vernonia amygdalina Delile in experimental models of Alzheimer’s disease. Drug and Chemical Toxicology. 2020; 43: 1-11. Available from: .
119. 119. Ijeh II, Nwugo VO, Obidoa O. Comparative studies on the nutritive, phytochemical and antimicrobial properties of two varieties of Vernonia amygdalina. Plant Processing Research Community. 1996; 1: 71-75.
120. 120. Akinpelu DA. Antimicrobial activity of Vernonia amygdalina leaves. Fitoterapia. 1999; 70: 432–434. Available from: .
121. 121. Kola OM. Anti-inflammatory activity of ethanolic leaf extract from Vernonia amygdalina on the immune system of Swiss Albino rats dosed with Clostridium sporogenes (NC13532). Research Journal of Medical Sciences. 2007; 1(2): 127-131.
122. 122. Muraina IA, Adaudi AO, Mamman M, McGaw LJ, Eloff JN. Antimycoplasmal activity of some plant species from northern Nigeria compared to the currently used therapeutic agent. Pharmaceutical Biology. 2010; 48(10): 1103-1107. Available from: .
123. 123. Sit NW, Chan YS, Lai SC, Khoo KS, Ong HC. In vitro antidermatophytic activity and cytotoxicity of extracts derived from medicinal plants and marine algae. Journal de Mycologie Medicale. 2018; 28(3): 561-567. Available from: .
124. 124. Vlietinck AJ, Hoof LV, Totte J, Lasure A, Berghe DV. Screening of hundred Rwandese medicinal plants for antimicrobial and antiviral properties. Journal of Ethnopharmacology. 1995; 46: 31-47. Available from: .
125. 125. Kraft C, Jenett-Siems K, Siems K, Jakupovic J, Mavi S et al. In vitro antiplasmodial evaluation of medicinal plants from Zimbabwe. Phytotherapeutic Research. 2003; 17: 123-128. Available from: .
126. 126. Toyang N, Verpoorte R. A review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology. 2013; 146: 681–723. Available from: .
127. 127. Oladeji OS, Oluyori AP, Bankole DT, Afolabi TY. Natural products as sources of antimalarial drugs: Ethnobotanical and ethnopharmacological studies. Scientifica. 2020; 2020(1): 1-22. Available from: .
128. 128. Masaba SC. The antimalarial activity of Vernonia amygdalina Del (Compositae). Transactions of Royal Society of Tropical Medicine Hygiene. 2000; 94: 694–695. Available from: .
129. 129. Omoregie ES, Pal A, Darokar MP, Chanda D, Sisodia B. In vitro and in vivo antiplasmodial activity and cytotoxicity of extracts from Vernonia amygdalina Del. leaves. Malaria Journal. 2010; 9(2): 30. Available from: .
130. 130. Lacroix D, Prado S, Kamoga D, Kasenene J, Namukobe J, Krief S. Antiplasmodial and cytotoxic activities of medicinal plants traditionally used in the village of Kiohima, Uganda. Journal of Ethnopharmacology. 2011; 133: 850–855. Available from: .
131. 131. Iwalokun BA. Enhanced antimalarial effects of chloroquine by aqueousVernonia amygdalina leaf extract in mice infected with chloroquine-resistant and chloroquine-sensitive Plasmodium berghei strains. African Health Science. 2008; 8(1): 25–35.
132. 132. Abosi AAO, Raseroka BHB. In vivo antimalarial activity of Vernonia amygdalina. British Journal of Biomedical Science. 2003; 60(2): 89–91. Available from: .
133. 133. Melariri P, Campbell W, Etusim P, Smith P. In vitro and in vivoantiplasmodial activities of extracts of Cymbopogon citratus Staph and Vernonia amygdalina Delile leaves. Journal of Natural Product. 2011; 4: 164–172. Available from: .
134. 134. Challand S, Willcox M. A clinical trial of the traditional medicine Vernonia amygdalina in the treatment of uncomplicated malaria. Journal of Alternative Complementary Medicine. 2009; 15: 1231–1237. Available from: .
135. 135. Njan AA, Adzu B, Agaba AG, Byarugaba D, Díaz-Llera S, Bangsberg DR. The analgesic and antiplasmodial activities and toxicology of Vernonia amygdalina. Journal of Medicinal Food. 2008; 11(3): 574-581. Available from: .
136. 136. Ijeh II, Obidoa O. Effect of dietary incorporation of Vernonia amygdalina Del. on AFB1-induced hepatotoxicity in weanling albino rats. Jamaican J. Sci. Tech. 2004; 15: 32-36.
137. 137. Ogunlade B, Akunna GG, Fatoba OO, Ayeni OJ, Adegoke AA, Adelakun SA. Aqueous extract of Vernonia amygdalina protects against alcohol-induced hepatotoxicity in Wistar rats. World J. Young Res. 2012; 2: 70.
138. 138. Singh M, Hussain T, Firdous H, Shaikh S, Rizvi SMD, Moin A, Khan M, Kamal MA. Preclinical hepatoprotective effect of herbalism against ethanol induced hepatotoxicity: A review. Current Drug. Metabolism. 2018; 19(12): 1002-1011. Available from: .
139. 139. Ijeh II, Obidoa O. Effects of dietary incorporation of two varieties of Vernonia amygdalina leaves on mean relative organ weight of weanling albino rats. Nigeria Journal of Biochemistry and Molecular Biology. 2001; 16: 50-51.
140. 140. Atangwho IJ, Ebong PE, Egbung GE, Ani IF. Effects of co-administration of Vernonia amygdalina and Azadirachta indica extracts on serum electrolyte profile of diabetic and non-diabetic rats. Australia Journal of Basic Applied Sciences. 2009; 3: 2974-2978.
141. 141. Achuba FI. Role of bitter leaf (Vernonia amygdalina) extract in prevention of renal toxicity induced by crude petroleum contaminated diets in rats. International Journal of Veterinary Science and Medicine. 2018; 6 (2): 172-177. Available from: .
142. 142. Adefisayo MA, Akomolafe RO, Akinsomisoye SO, Alabi QK, Ogundipe OL, Omole JG, Olamilosoye KP. Gastro-protective effect of methanol extract of Vernonia amygdalina (del.) leaf on aspirin-induced gastric ulcer in Wistar rats. Toxicology Reports. 2017; 4: 625-633. Available from: .
143. 143. Huffman MA, Seifu M. "Observations on the illness and consumption of a possibly medicinal plant Vernonia amygdalina (Del.), by a wild chimpanzee in the Mahale Mountains National Park, Tanzania". Primates. 1989; 30: 51–63. Available from: .
144. 144. Huffman MA, Page JE, Sukhadeo MVK, Gotoh S, Kalunde MS, Towers GH. Leaf swallowing by chimpanzees: A behavioural adaptation for the control of strong nematode infections. International Journal of Rrimatology. 1996; 72: 475-503. Available from: .
145. 145. Engel C. Zoopharmacognosy. Veterinary Herbal Medicine. 2007; 2: 7–15.
146. 146. Fred-Jaiyesimi A, Ajibesin KK, Odeyemi T, Ogundokun G. Ethnobotanical studies of folklore phytocosmetics of South West Nigeria. Pharmaceutical Biology. 2015; 53(3): 313-318. Available from: .
147. 147. Mohammad IS, Naveed M, Ijaz S, Shumzaid M, Hassan S, Muhammad KS, Rasoolg F, Akhtarh N, Ishaq HF, Khan HMS. Phytocosmeceutical formulation development, characterization and its in-vivo investigations. Biomedicine & Pharmacotherapy. 2018; 107: 806–817. Available from: .
148. 148. Atolani O, Oguntoye H, Areh ET, Adeyemi OS, Kambizi L. Chemical composition, anti-toxoplasma, cytotoxicity, antioxidant, and anti- inflammatory potential of Cola gigantea seed oil. Pharmaceutical Biology. 2019a; 57(1): 154–160. Available from: .
149. 149. Atolani O, Areh ET, Oguntoye OS, Zubair MF, Fabiyi OA, Oyegoke RA, Tarigha DE, Adamu N, Adeyemi OS, Kambizi L, Olatunji GA. Chemical composition, antioxidant, anti-lipooxygenase, antimicrobial, anti-parasite and cytotoxicity of Polyalthia longifolia seed oil. Medicinal Chemistry research. (2019b); 28 (3): 515-527. Available from: .
150. 150. Osho A, Otuechere CA, Adeosun CB, Oluwagbemi T, Atolani O. Phytochemical, sub-acute toxicity, and antibacterial evaluation of Cordia sebestena leaf extracts. Journal of basic and clinical physiology and pharmacology. 2015; 27(2): 163-170. Available from: .
151. 151. Fongnzossie EF, Tize Z, Fogang Nde PJ, Nyangono Biyegue CF, Bouelet Ntsama IS, Dibong SD, Nkongmeneck BA. Ethnobotany and pharmacognostic perspective of plant species used as traditional cosmetics and cosmeceuticals among the Gbaya ethnic group in Eastern Cameroon. South African Journal of Botany. 2017; 112: 29–39. Available from: .
152. 152. Oloke J, Odelade K, Oladeji O. Characterization and Antimicrobial Analysis of Flavonoids in Vernonia Amygdalina: A Common Chewing Stick In South-Western Nigeria. Bulletin of Pharmaceutical Research. 2017; 7(3): 149. DOI: 10.21276/bpr.2017.7.3.2
153. 153. Ndukwe K, Okeke IN, Lamikanra A, Adesina SK, Aboderin O. Antibacterial activity of aqueous extracts of selected chewing sticks. Journal of Contemporary Dental Practice. 2005; 6(3): 1-8.
154. 154. Bullough CHW, Leary WP. Herbal medicines used by traditional birth attendants in Malawi. Tropical and Geographical Medicine. 1982; 34: 81–85.
155. 155. Kamatenesi-Mugisha M. Medicinal plants used in reproductive health care in Western Uganda: Documentation, phytochemical and bioactivity evaluation. PhD Thesis in Botany, Makerere University, Kampala, Uganda. 2004.
156. 156. Kamatenesi-Mugisha M, Oryem-Origa H, Makawiti OO. Ethnopharmacological screening of Vernonia amygdalina and Cleome gynandra traditionally used in childbirth in Western Uganda. Proc 11th NAPRECA Symposium, Antanarivo, Madagascar. 2005; 110-122. Available from: .
157. 157. Ijeh II, Igwe KK, Ejike CECC. Effect of leaf aqueous extracts of Vernonia amygdalina Del. on contraction of mammary gland and uterus of guinea pig dams. Journal of Herbs, Spices and Medicinal Plants. 2010; 1: 107-116. Available from: .
158. 158. Ibrahim G, Abdurahman E, Ibrahim H, Ibrahim N, Magaji M. Toxicity and analgesic effects of Vernonia amygdalina Del. (Asteraceae) leaf extract on mice. International Journal of Advanced Pharmaceutical and Biological Sciences. 2011; 1: 1–4.
159. 159. Lelago A, Ekero D, Keshebo DL. Isolation of Sesquiterpene from the Leaves Extract of Vernonia amygdalina and Its Acute Toxicity to the Albino Mice. Chemistry and Materials Research. 2016; 8(6): 56-60.
160. 160. Asawalam EF, Emosairue SO, Hassanali A. Contribution of different constituents to the toxicity of the essential oil constituents of Vernonia amygdalina (compositae) and xylopia aetiopica (annonaceae) on maize weevil, Sitophilus zeamais motschulsky (coleoptera: Curculionidae). African Journal of Biotechnology 2008; 7(16): 2957-2962.
161. 161. Imafidon CE, Olukiran OS, Ogundipe DJ, Eluwole AO, Adekunle IA, Oke GO. Acetonic extract of Vernonia amygdalina (Del.) attenuates Cd-induced liver injury: Potential application in adjuvant heavy metal therapy. Toxicology Reports. 2018; 5: 324-332. Available from: .
162. 162. Kimani NM, Matasyoh JC, Kaiser M, Brun R, Schmidt TJ. Sesquiterpene lactone from Vernonia cinerascens Sch. Bip. and their in vitro antitrypanosomal activity. Molecule. 2018; 23(2):248. Available from: .
163. 163. Degu A, Kefale B, Alemayehu D, Tegegne GT. Evaluation of the Antidiarrheal Activity of Hydromethanol Crude Extracts of Ruta chalepensis and Vernonia amygdalina in Mice. Evidence-based Complementary and Alternative Medicine. 2020; 2020(2): 1-6. Available from: .
164. 164. Olayemi AA, Temitope AO, David KB. Evaluation of antidiarrheal activity of the ethanolic stem bark extract of Vernonia amygdalina in experimental animals. Journal of Natural Sciences Research. 2016; 6 (10): 61-66.
165. 165. Awe SO, Makinde JM, Olajide OA. Cathartic effect of the leaf extract of Vernonia amygdalina. Fitoterapia. 1999; 70(2): 161-165. Available from: .
166. 166. Obbo CJD, Kariuki ST, Gathirwa JW, Cheplogoi PK, Mwangi EM. In vitro antiplasmodial, antitrypanosomal and antileishmanial activities of selected medicinal plants from Ugandan flora: Refocusing into multi-component potentials. Journal of Ethnopharmacology. 2019; 229: 127-136. Available from: .
167. 167. Ocheng F, Bwanga F, Joloba M, Softrata A, Azeem M, Pütsep K, Borg- Karlson AK, Obua C, Gustafsson A. Essential oils from ugandan aromatic medicinal plants: Chemical composition and growth inhibitory effects on oral pathogens. Evidence-Based Complementary and Alternative Medicine. 2015; 2015(4): 1-10. Available from: .
168. 168. Bacha K, Tariku Y, Gebreyesus F, Schmitz RA, Mulat M. Antimicrobial and anti-Quorum Sensing activities of selected medicinal plants of Ethiopia: Implication for development of potent antimicrobial agents. BioMed Central Microbiology. 2016; 16 (1): 139. Available from: .