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

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.

[1]  S. Gautam,et al.  Evaluation of Toxicity and Antihyperlipidemic Activity of Spondias Mombin l. Leaves Methanolic Extract in Laboratory Rats. , 2020, Cardiovascular & hematological disorders drug targets.

[2]  O. Ogbole,et al.  Medicinal Plants Used in Four Local Government Areas of Southwestern Nigeria for the Management of Diabetes and Its Comorbidities: An Ethnobotanical Survey , 2020 .

[3]  A. Elujoba,et al.  Antihyperglycaemic and antioxidant activities of Sansevierialiberica as justification for its antidiabetic claims , 2020 .

[4]  F. Zotor,et al.  Justifying Antidiabetic Ethnomedicinal Claim of Senecio biafrae through Its Antihyperglycemic and Anti-Oxidant Activities , 2019 .

[5]  A. C. Adebajo,et al.  Anti-hyperglycaemic and anti-oxidant activities of five Nigerian antidiabetic plants , 2019, Journal of Science and Technology (Ghana).

[6]  Vivian Charles McAlister,et al.  Bidirectional graft-host hematological traffic in liver transplantation. , 2019, Hepatobiliary surgery and nutrition.

[7]  A. Ore,et al.  Median Lethality Dose of Xylopia aethiopica Fruit Ethanol Extract , 2019, Journal of Analytical Techniques and Research.

[8]  A. Feyisayo,et al.  Anti-hyperglycaemic, anti-inflammatory and anti-oxidant activities of Carica papaya and Citrullus lanatus seeds , 2018, Ife Journal of Science.

[9]  A. Boligon,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 , 2018, Food science & nutrition.

[10]  O. Adeyemi,et al.  Protective role of Spondias mombin leaf and Cola acuminata seed extracts against scopolamine-induced cognitive dysfunction , 2018 .

[11]  F. Famuyiwa,et al.  Hyperglycaemia Lowering Effect of Kaurane Diterpenoids from the Fruits of Xylopia aethiopica (A. Dunal) Rich , 2018 .

[12]  M. Islam,et al.  Antioxidant potential of Xylopia aethiopica fruit acetone fraction in a type 2 diabetes model of rats. , 2017, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[13]  M. Faramarzi,et al.  Effects of an Herbal Combination on Glycemic Control and Lipid Profile in Diabetic Women: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial , 2017, Journal of evidence-based complementary & alternative medicine.

[14]  S. Yeboah,et al.  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 , 2017 .

[15]  K. Akinwunmi,et al.  Anti-diabetic and antioxidant activities of Entandrophragma cylindricum and Triclisia subcordata , 2017 .

[16]  R. B. Giordani,et al.  Phytochemical study and anti-inflammatory and antioxidant potential of Spondias mombin leaves , 2016 .

[17]  P. Thangaraj.  Anti-diabetic Activity. , 2016, Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques.

[18]  P. Malathi,et al.  Evaluation of mosquito larvicidal effect of Carica Papaya against Aedes Aegypti , 2015 .

[19]  B. Lawal,et al.  Effect of Methanol Extract of Telfairia occcidentalis on Haematological Parameters in Wister Rats , 2015 .

[20]  Dileep Kumar,et al.  Efficacy of Composite Extract from Leaves and Fruits of Medicinal Plants Used in Traditional Diabetic Therapy against Oxidative Stress in Alloxan-Induced Diabetic Rats , 2014, ISRN pharmacology.

[21]  B. Ajiboye,et al.  Effect of aqueous leaf extract of Senecio biafrae on hyperglycaemic and serum lipid profile of alloxan-induced diabetic rats , 2014 .

[22]  C. Ejike,et al.  Synergistic postprandial blood glucose modulatory properties of Vernonia amygdalina (Del.), Gongronema latifolium (Benth.) and Occimum gratissimum (Linn.) aqueous decoctions. , 2013, Journal of ethnopharmacology.

[23]  Ayoola,et al.  Antihyperglycaemic and Anti-oxidant Activities of Eugenia uniflora Leaf: Evaluation of Ethnomedical Claims IV , 2013 .

[24]  Chun-Tao Che,et al.  Herb-Herb Combination for Therapeutic Enhancement and Advancement: Theory, Practice and Future Perspectives , 2013, Molecules.

[25]  I. Gbadamosi,et al.  Botanical galactogogues: nutritional values and therapeutic potentials , 2013 .

[26]  C. Rosak,et al.  Critical evaluation of the role of acarbose in the treatment of diabetes: patient considerations , 2012, Diabetes, metabolic syndrome and obesity : targets and therapy.

[27]  A. Ramachandran,et al.  Hepatoprotective potential of polyphenol rich extract of Murraya koenigii L.: an in vivo study. , 2012, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[28]  L. Jian-ping.  Critical Evaluation of the Role of Acarbose in the Treatment of Diabetes:Patient Considerations , 2012 .

[29]  M. Ngugi,et al.  Pharmacological Management of Diabetes Mellitus. , 2012 .

[30]  T. Idowu,et al.  HAEMATOLOGICAL RESPONSE TO INTAKE OF UNRIPE CARICA PAPAYA FRUIT EXTRACT AND THE ISOLATION AND CHARACTERIZATION OF CARICAPINOSIDE: A NEW ANTISICKLING AGENT FROM THE EXTRACT , 2012 .

[31]  B. Ducommun,et al.  Characterization of the antiproliferative activity of Xylopia aethiopica , 2012, Cell Division.

[32]  O. Akinola,et al.  Effects of combined leaf extract of Vernonia amygdalina and Azadirachta indica on hepatic morphology and hepatotoxicity markers in streptozotocin-induced diabetic rats. , 2011, Zhong xi yi jie he xue bao = Journal of Chinese integrative medicine.

[33]  O. Adaramoye,et al.  Hypolipidemic and antioxidant potentials of Xylopia aethiopica seed extract in hypercholesterolemic rats. , 2011, Journal of medicinal food.

[34]  O. Oloyede,et al.  Performance and haematological indices in rats exposed to monocrotophos contamination , 2010, Human & experimental toxicology.

[35]  Y. Kong.  Huangdi Neijing: A Synopsis with Commentaries , 2010 .

[36]  G. Mbaka,et al.  Effect of a poly-herbal formulation, Okudiabet, on alloxan-induced diabetic rats. , 2010 .

[37]  O. Ogbole,et al.  Traditional management of tuberculosis in Ogun State of Nigeria: the practice and ethnobotanical survey. , 2010, African journal of traditional, complementary, and alternative medicines : AJTCAM.

[38]  M. A. Ayoola,et al.  ANTIDIABETIC ACTIVITY OF ETHANOLIC EXTRACTS OF SPONDIAS MOMBIN (ANACARDIACEAE) STEM BARK ON ALLOXAN-INDUCED DIABETIC RATS , 2009 .

[39]  Rafael Radi,et al.  Chemical biology of peroxynitrite: kinetics, diffusion, and radicals. , 2009, ACS chemical biology.

[40]  E. Verspohl,et al.  Pharmacological properties of the extract and some isolated compounds of Clausena lansium stem bark: anti-trichomonal, antidiabetic, anti-inflammatory, hepatoprotective and antioxidant effects. , 2009, Journal of ethnopharmacology.

[41]  A. Gbolade.  Inventory of antidiabetic plants in selected districts of Lagos State, Nigeria. , 2009, Journal of ethnopharmacology.

[42]  E. Etuk,et al.  Informant consensus selection method: a reliability assessment on medicinal plants used in north western Nigeria for the treatment of diabetes mellitus. , 2009 .

[43]  B. Nwiloh,et al.  Effects of Aqueous Extract of Mangifera indica L. (Mango) Stem Bark on Haematological Parameters of Normal Albino Rats , 2008 .

[44]  OECD GUIDELINES FOR THE TESTING OF CHEMICALS , 2008 .

[45]  E. Verspohl,et al.  Antidiabetic effect of Cinnamomum cassia and Cinnamomum zeylanicum In vivo and In vitro , 2005, Phytotherapy research : PTR.

[46]  Y. Jang,et al.  Standards of Medical Care in Diabetes-2010 by the American Diabetes Association: Prevention and Management of Cardiovascular Disease , 2010 .

[47]  S. Withers,et al.  Detailed Dissection of a New Mechanism for Glycoside Cleavage: α-1,4-Glucan Lyase† , 2003 .

[48]  E. Verspohl,et al.  Recommended Testing in Diabetes Research , 2002, Planta medica.

[49]  John S. Williams,et al.  Industrial solvents and liver toxicity: risk assessment, risk factors and mechanisms. , 2002, International journal of hygiene and environmental health.

[50]  R. Schippers.  African Indigenous Vegetables: An overview of the cultivated species. , 2000 .

[51]  P. Prieto,et al.  Spectrophotometric quantitation of antioxidant capacity through the formation of a phosphomolybdenum complex: specific application to the determination of vitamin E. , 1999, Analytical biochemistry.

[52]  Mengcheng Tang,et al.  The determination of flavonoid contents in mulberry and their scavenging effects on superoxide radicals , 1999 .

[53]  A. Kar,et al.  Preliminary studies on the inorganic constituents of some indigenous hypoglycaemic herbs on oral glucose tolerance test. , 1999, Journal of ethnopharmacology.

[54]  R. Lamuela-Raventós,et al.  Analysis of total phenols and other oxidation substrates and antioxidants by means of Folin-Ciocalteu reagent , 1999 .

[55]  L. Luzi,et al.  Glibenclamide: an old drug with a novel mechanism of action? , 1997, Acta Diabetologica.

[56]  C. Berset,et al.  Use of a Free Radical Method to Evaluate Antioxidant Activity , 1995 .

[57]  C. Dolea,et al.  World Health Organization , 1949, International Organization.

[58]  G. Miliauskasa,et al.  Screening of radical scavenging activity of some medicinal and aromatic plant extracts , 2022 .