Antidiabetic and Toxicity Studies of the Extract of Four Nigerian Medicinal Plants

Oyenike Idayat Bello

Department of Pharmacognosy, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria.

Marcus Durojaye Ayoola *

Department of Pharmacognosy, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria.

Oluwafunke Obembe

Department of Pharmacognosy, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria.

Kemi Feyisayo Akinwunmi

Department of Biochemistry and Molecular Biology, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria.

*Author to whom correspondence should be addressed.


Aims: To evaluate the anti-hyperglycaemic efficacy and safety of the methanol extract of the combination of Senecio biafrae leaf, Xylopia aethiopica fruit, Carica papaya seed and Spondias mombin stem bark mixed together in ratio 1:1:1:1

Study Design: Extract of medicinal plants was assayed using glucose and streptozotocin-induced herperglycaemic rats model.

Place and Duration of Study: Department of Pharmacognosy, Obafemi Awolowo University, IleIfe, Nigeria, between May, 2019 and January, 2022.

Methodology: The extract of the combined plant parts was tested for toxicity in rats while its effects on glucose level, blood and biochemical components were also assessed. Its in-vitro anti-hyperglycaemic activity was assayed in α-amylase and α-glucosidase inhibitory models while its in-vivo effects were tested in glucose and streptozotocin-induced hyperglycaemic rats. The antioxidant activity of the extract was also carried out.

Results: The extract did not show any adverse effects on blood sugar levels, haematological and biochemical parameters in normal rats in sub acute toxicity tests. The extract gave comparable (p > 0.05) α-amylase and α-glucosidase inhibitory effects to acarbose. In glucose-induced hyperglycaemic rats, its 100 mg/kg was the most effective dose with 19, 40, 43, and 57%  activity  that was significantly higher (p < 0.05) than the 10, 18, 24, and 40%  activity given by glibenclamide (5 mg/kg) at the same time points. In streptozotocin-induced diabetic assay, its 50 mg/kg showed 31, 85, 85 and 82 % effects on days 4, 7, 10 and 14, respectively that was significantly higher than its 100 mg/kg and glibenclamide on days 7 and 10.  The extract also elicited high free radical scavenging effects in all the antioxidant assays.

Conclusion: The extract of the combination of four Nigerian antidiabetic plants mixed together in equal ratio gave significantly better antidiabetic activity at low doses than the individual plants without toxic effects.

Keywords: Diabetes mellitus, anti-hyperglycaemic effect, plant combination, antioxidant activity

How to Cite

Bello, O. I., Ayoola, M. D., Obembe, O., & Akinwunmi, K. F. (2022). Antidiabetic and Toxicity Studies of the Extract of Four Nigerian Medicinal Plants. European Journal of Medicinal Plants, 33(11), 32–45.


World Health Organization (WHO). Global Report on Diabetes. 2016;88.

American Diabetes Association (ADA). Classification and diagnosis of diabetes: Standards of medical care in diabetes. Diabetes Care. 2021;44(Suppl. 1):S15-S33.

World Health Organization. The Global Diabetes Compact. 2021b;1-7.

International Diabetes Federation. Diabetes Atlas. 3rd ed. Belgium: B-1000 Brussels, 19 Avenue Emile de Mot. 2006; 387.

Faloye KO, Ayoola MD, Amos-Tautua BM, Famuyiwa SO. Anti-diabetic activity of convallatoxin isolated from the root bark of Parquetina nigrescens (Afzel.) Bullock (Asclepiadaceae). European Journal of Medicinal Plants. 2018;25(4):1-9.

Ayoola MD, Oriola AO, Faloye KO, Aladesanmi AJ. Justifying the antidiabetic ethnomedicinal claim of Massularia acuminata through its antihyperglycaemic activity. Am J Biomed Sci & Res. 2020; 8(2):76-258.

Ajileye AJ, Ayoola MD, Elujoba AA, Akinwunmi KF. Antihyperglycaemic and antioxidant activities of Sansevieria liberica as justification for its antidiabetic claims. Afr. J. Pharm. Pharmacol. 2020;14(3):59-66.

Che CT, Wang ZJ, Chow MS, Lam CW. Herb-herb combination for therapeutic enhancement and advancement: Theory, practice and future perspectives. Molecules. 2013;18(5):5125-5141.

Kong YC. Huangdi Neijing, A synopsis with commentaries. The Chinese University Press: Hong Kong, China; 2010.

Ogbonnia SO, Mbaka GO, Adekunle A, Anyika EN, Gbolade OE, Nwakakwa N. Effect of a poly-herbal formulation, Okudiabet, on alloxan-induced diabetic rats. Agric Biol J North Am. 2010;1:139-145.

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. PubMed. 2011;9:1373-1379.

Ejike CE, Awazie SO, Nwangozi PA, Godwin CD. Synergistic postprandial blood glucose modulatory properties of Vernonia amygdalina (Del.), Gongronema latifolium (Benth.) and Occimum gratissimum (Linn.) aqueous decoctions. J. Ethnopharmacology. 2013;149: 111-116.

Tiwari BK, Kumar, D, Abidi AB, Rizvi SI. Efficacy of composite extract from leaves and fruits of medicinal plants used in traditional diabetic therapy against oxidative stress in alloxan-induced diabetic rats. ISRN Pharmacol. 2014;608590.

Etuk EU, Mohammed BJ. Informant consensus selection method: A reliability assessment on medicinal plants used in north western Nigeria for the treatment of diabetes mellitus. African Journal of Pharmacy and Pharmacology. 2019;3(10): 496-500.

Shokoohi R, Kianbakht S, Faramarzi M, Rahmanian M, Nabati F, Mehrzadi S, et al. Effects of an Herbal Combination on Glycemic Control and Lipid Profile in Diabetic Women: A randomized, double-blind, placebo-controlled clinical trial. Journal of Evidence-Based Complementary & Alternative Medicine. 2017;22(4):798-804.

Schippers RR. African indigenous vegetables. An overview of the cultivated species. Chatham, United Kingdom: Natural Resources Institute/ACP-EU Technical Centre for Agricultural and Rural Cooperation; 2000.

Gbadamosi IT, Okolosi O. Botanical galactogogues: Nutritional values and therapeutic potentials. J. Appl Biosci. 2013;61:4460-4469.

Gbolade AA. Inventory of antidiabetic plants in selected districts of Lagos State, Nigeria. J. Ethnopharmacol. 2008;121(1): 135-139.

Ajiboye BO, Ojo OA, Okesola MA, Akinyemi AJ, Talabi JY. Idowu OT, et al. In-vitro antioxidant activities and inhibitory effects of phenolic extract of Senecio biafrae (Oliv and Hiern) against key enzymes linked with type II diabetes mellitus and Alzheimer’s disease. Food Sci Nutr. 2018;6:1803–1810.

Ajiboye BO, Edobor G, Ojo AO, Onikanni SA, Olaranwaju OI, Muhammad NO. Effect of aqueous leaf extract of Senecio biafrae on hyperglycaemic and serum lipid profile of alloxan-induced diabetic rats. International Journal of Diseases and Disorders. 2014;2(1):59-64.

Ayoola MD, Adebajo AC, Zotor FB, Pinkoane MG. Justifying antidiabetic ethnomedicinal claim of Senecio biafrae through its antihyperglycemic and antioxidant activities. Ann Complement Altern Med. 2019;1(2):1006.

Sidiq LO, Segun PA, Ogbole OO. Medicinal plants used in four Local Government Areas of Southwestern Nigeria for the management of diabetes and its comorbidities: An ethnobotanical survey. Research Square. 2020;1-17.

Famuyiwa FG, Ayoola, MD, Famuyiwa SO, Aladesanmi AJ. Hyperglycaemia lowering effect of Kaurane Diterpenoids from the fruits of Xylopia aethiopica (A. Dunal) Rich. International Journal of Medicinal Plants and Natural Products (IJMPNP). 2018; 4(3):11-19.

Choumessi AT, Danel M, Chassaing S, Truchet I, Penlap VB, Pieme AC. et al. Characterization of the antiproliferative activity of Xylopia aethiopica. Cell Div. 2012;7(1),8.

Nwozo SO, Orojobi BF, Adaramoye OA. Hypolipidemic and antioxidant potentials of Xylopia aethiopica seed extract in hypercholesterolemic rats. J Med Food. 2011;14(1-2):114-149.

Akinwunmi KF, Ayoola MD. Anti-hyperglycaemic, anti-inflammatory and anti-oxidant activities of Carica papaya and Citrullus lanatus seeds. Ife Journal of Science. 2018;20(2):207-218.

Malathi P, Vasugi SR. Evaluation of mosquito larvicidal effect of Carica papaya against Aedes aegypti. Int. J. Mosq. Res. 2015;2(3):21-24.

Oduola T, Idowu TO, Bello IS, Adeniyi F, Ogunyemi E. Haematological response to intake of unripe Carica papaya fruit extract and the isolation and characterization of caricapinoside: A new antisickling agent from the extract. Asian J. Pharm. Clin. Res. 2012;5(Suppl 3):77-81.

Ogbole OO, Ajaiyeoba EO. Traditional management of tuberculosis in Ogun State of Nigeria: The practice and ethnobotanical survey. Afr. J. Trad. CAM. 2010;7(1):79-84.

Mohammed A, Islam MS. Antioxidant potential of Xylopia aethiopica fruit acetone fraction in a type 2 diabetes model of rats. Biomed Pharmacother. 2017;96;30-36.

Gbolade A, Ekor M, Akinlolu A, Ayoola MD. Antidiabetic activity of ethanolic extracts of Spondias mombin (Anacardiaceae) stem bark on alloxan-induced diabetic rats. African Journal of Traditional, Complementary and Alternative Medicines. 2009;6:437.

OECD. The OECD guidelines for the testing of chemicals: 423. Acute Oral Toxicity – Acute Toxic Class Method; 2001.

OECD. The OECD guidelines for the testing of chemicals: 407. Repeated dose 28-day oral toxicity study in rodents; 2008.

Sharma H, Tun-Abraham ME, McAlister V. Bidirectional graft-host hematological traffic in liver transplantation. Hepatobiliary Surgery and Nutrition. 2019;8:253.

Bahman N, Leyla A, Hamidreza I. Alpha-amylase inhibitory activities of six Salvia spp. Iranian J. Pharm. Res. 2008;7:297-303.

Jain C, Kumar P, Singh A, Jindal A. In vitro comparisons of anti-diabetic activity of drugs used for the treatment of diabetes. Journal Clinical Biochemistry Nutrition. 2013;40:163–167.

Li T, Zhang XD, Song YW. A microplate-based screening method for alpha-glucosidase inhibitors. Chinese Chin J Clin Pharmaco Ther. 2005;10:1128-1134.

Adebajo AC, Iwalewa EO, Obuotor EM, Ibikunle GF, Omisore NO, Adewunmi CO, et al. Pharmacological properties of the extract and some isolated compounds of Clausena lansium stem bark: Antitrichomonal, anti-diabetic, anti-inflammatory, hepatoprotective and antioxidant effects. J Ethnopharmacol. 2009;122(1):10-19.

Adebajo AC, Ayoola MD, Odediran SA, Aladesanmi AJ, Schmidt TJ, Verspohl EJ. Evaluation of ethnomedical claims III: Antihyperglycaemic activities of Gongronema latifolium root and stem. J Diabetes. 2013a;5(3):336-343.

Adebajo AC, Ayoola MD, Obagbemi OR, Obuotor EM, Ogunsina MO, Verspohl EJ. Antihyperglycaemic and antioxidant activities of Eugenia uniflora leaf: Evaluation of ethnomedical claims IV. Ife J Sci Technol. 2013b;1(1):1-18.

Ayoola MD, Adebajo AC, Obuotor EM, Oladapo TO, Fleischer TC. Antihyperglycaemic and anti-oxidant activities of five Nigerian antidiabetic plants. J Sci Technol. (Ghana). 2017;37(2): 71-84.

Brand-Williams W, Cuvelier ME, Berset C. Use of a free radical method to evaluate antioxidant activity. LWT- Food Science and Technology. 1995;28:25-30.

Prieto P, Pineda M, Aguilar M. Spectrophotometric quantification of antioxidant capacity through the formation of a phosphomolybdenum complex: Specific application to the determination of vitamin E. Anal Biochemistry. 1999;269(2): 337-41.

Benzie IFF, Strain JJ. Ferric reducing (antioxidant) power as a measure of antioxidant capacity: The FRAP assay. Methods Enzymol. 1999;299:15-36.

Ferrer-Sueta G, Radi R. Chemical biology of peroxynitrite: Kinetics, diffusion, and radicals. ACS Chemical Biology. 2009; 4(3):161-77.

Zhilen J, Mengeheng T, Jianming W. The determination of flavonoid contents in mulberry and their scavenging effects on superoxide radicals. Food Chemistry. 1999;64:555-559.

Miliauskas G, Venskutonis PR, Van Beek TA. Screening of radical scavenging activity of some medicinal and aromatic plant extract. Food Chemistry. 2004;88: 231-237.

Singleton VL, Rudolf O, Lamuela-Raventos RM. Analysis of total phenols and other oxidation substrates and antioxidants by means of Folin-Ciocalteu reagent. Methods in Enzymology. 1999;299:152-178.

Gulcin I, Sat, GI, Beydemir S, Elemastas M, Kfrevioglu OI. Comparison of antioxidant activity of clove (Eugenia caryophylata Thumb) buds and lavender (Lavender stoechas L.). Food Chemistry. 2003;87:393-400.

Halim SZ, Abdullah NR, Afzan A, Abdul Rashid BA, Jantan I, Ismail Z. Acute toxicity study of Carica papaya leaf extract in Sprague Dawley rats. Journal of Medicinal Plants Research. 2011;5(20): 1867-1872.

Ayodele PF, Ore A, Akinloye OA. Median lethality dose of Xylopia aethiopica fruit ethanol extract. J Anal Tech Res. 2019; 1(1):33-36.

Powal M, Gautam SK, Khan NA, Maheshwari KK. Evaluation of toxicity and antihyperlipidemic activity of Spodias mombin leaves methanolic extract in laboratory rats. Cardiovasc Hematol Disord Drug Targets. 2020;20(4):289-296.

Ayoola MD, Akinwunmi KF, Agboola OB. Anti-diabetic and antioxidant activities of Entandrophragma cylindricum and Triclisia subcordata. Nigerian Journal of Natural Products and Medicine. 2017b;21:24-31.

Ayoola MD, Balogun, JO, Famuyiwa FG, Yeboah SO, Famuyiwa SO. Isolation and characterization of 2-hydroxy-3-[4-hydroxyphenyl]-2-propenoic acid and 4-bromophenol from anti-diabetic extract of the root bark of Uvaria afzelii. South African Journal of Botany. 2017c;112:527–532.

Sunmonu TO, and Oloyede OB. Performance and haematological indices in rats exposed to monocrotophos contamination. Human & Experimental Toxicology. 2010;29:845-50.

Nwinuka NM, Michael OM, Nwiloh BI. Effects of aqueous extract of Mangifera indica L.(Mango) stem bark on haematological parameters of normal albino rats. Pakistan Journal of Nutrition. 2008;7:663-66.

Bashir L, Shittu OK, Rotimi AA, Olalekan IA, Kamooru AA, Ossai PC. Effect of methanol extract of Telfairia occcidentalis on haematological parameters in Wister rats. J. Med. Sci. 2015;15(5):246-250.

Brautbar N, Williams J. Industrial solvents and liver toxicity: Risk assessment, risk factors and mechanisms. International Journal of Hygiene and Environmental Health. 2002;205:479-91.

Desai SN, Patel DK, Devkar RV, Patel PV, Ramachandran AV. Hepatoprotective potential of polyphenol rich extract of Murraya koenigii L.: An in vivo study. Food and Chemical Toxicology. 2012;50(2):310-314.

Lee SS, Yu S, Withers SG. Detailed dissection of a new mechanism for glycoside cleavage: α-1,4-Glucan Lyase. Biochemistry. 2003;42(44):13081–13090.

Ngugi M, Njagi J, Kibiti C, Mwenda M. Pharmacological management of diabetes mellitus. Asian Journal of Biochemical and Pharmaceutical Research. 2012;2: 2012.

Derosa G, Maffioli P. Mini-special issue paper management of diabetes patients with hypoglycaemic agents α-Glucosidase inhibitors and their use in clinical practice. Arch. Med. Sci. 2012;5: 899-906.

Rosak C, Mertes. Critical evaluation of the role of acarbose in the treatment of diabetes: Patient considerations. Diabetes, metabolic syndrome and obesity: Targets and Therapy. 2012;1:357.

Verspohl EJ, Bauer K, Neddermann E. Antidiabetic effect of Cinnamomum cassia and Cinnamomum zeylanicum in vivo and in vitro. Phytother Res. 2005;19(3):203-206.

Verspohl EJ. Recommended testing in diabetes research. Planta Med. 2002; 68(7):581-590.

Kar A, Choudhary BK, Bandyopadhyay NG. Preliminary studies on the inorganic constituents of some indigenous hypoglycaemic herbs on oral glucose tolerance test. J Ethnopharmacol. 1999; 64(2):179-184.

Luzi L, Pozza G. Glibenclamide: An old drug with a novel mechanism of action? Acta Diabetol. 1997;34(4): 239-244.

Ishola IO, Ikuomola BO, Adeyemi OO. Protective role of Spondias mombin leaf and Cola acuminata seed extracts against scopolamine-induced cognitive dysfunction. Alexandria Journal of Medicine. 2018;54(1):27–39.

Cabral B, Siqueira EMS, Bitencourt MAO, Lima MC, Lima AK, Ortmann CF, et al. Phytochemical study and anti-inflammatory and antioxidant potential of Spondias mombin leaves. Revista Brasileira de Farmacognosia. 2016;26(3): 304–311.