EVALUATION OF COMBINATION EFFECT ONTOXICITY AND ANTIDIABETIC POTENTIAL OF GYMNEMA SYLVESTRER. Br. AND COMBRETUM MICRANTHUM Fam. LEAF EXTRACTS
EVALUATION OF COMBINATION EFFECT ONTOXICITY AND ANTIDIABETIC POTENTIAL OF GYMNEMA SYLVESTRER. Br. AND COMBRETUM MICRANTHUM Fam. LEAF EXTRACTS
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Date
2017-07
Authors
IBRAHIM, Aminu
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Abstract
Plants like Gymnema sylvestre R.Br. (―periploca of the woods‖ in English; ―Kafisuga‖ in Hausa) (Asclepiadaceae) and Combretum micranthum, Fam. (Géézà in Hausa) (Combretaceae)) are used in combination for the management of diabetes mellitus (DM) in the North-Eastern part of Nigeria with little or no scientific basis. It is thus the aim of this research to validate the antidiabeticactivities of G. sylvestre (GS) andC. micranthum (CM) leaf extracts, individually and in combined form (GSCM). The study assayed for acute toxicity (LD50) and sub-chronic toxicity (various markers) indices. In vivoantidiabetic potential wasanalyzed by following fasting blood glucose (FBG), feed and water intakes, lipid profile, serum insulin and liver hexokinase levels. Fasting blood glucose, inhibitory activities of α-amylase and α-glucosidase and phytochemical contents were used to initially direct the column chromatography fractionation. Further fractionation and isolation (Preparative-TLC) was guided by FBG and the characterization/identification of compounds done byUltra-High-Performance Liquid Chromatography Electrospray Ionization Quadrupole-Time-of-Flight Tandem Mass Spectrometry (UHPLC-ESI-Q-TOF-MS/MS), NMR and FTIR. Both plants were found to be relatively safe (LD50 > 5000mg/kg) in mice. Sub-chronic toxicity studies revealed that GSCM (1:1) reversed body weight loss of the diabetic rats at 600mg/kg b.w. dose when compared with control after 3 weeks of administration. The increases in relative organ weights (liver and kidney) were reversed significantly (P < 0.05);Hb, MCHand MCHC increased; serum total protein increased; levels of liver MDA, SOD, ROSandCAT and serum ALTand ALP showed a general reduction trend with a concomitant increase in liver GSH, GSSG andGSH-Px when ―diabetic + treatment‖ groups were compared with the diabetic control. Moreover, GS and CM revealed good FRAP and radical scavenging activities against ABTS, DPPH and Nitric Oxide with C. micranthum being significantly better - both plants also showed good total flavonoids and total phenolic contents. Feed and water intake were reversed in the treated groups with percentage reductions of between 28 and 57 (for feed) and 14 and 39 (for water), with GSCM (1:1) displaying some dose-dependency. Fasting blood glucose for the 21 days experiment showed some significant reductions with the ―diabetic + 400GS‖ group giving the highest percentage of 65. Serum Total Cholesterol, LDL, VLDL and TG in the ―diabetes + treatment‖ groups showed general reduction whilst HDLincreases when compared with diabetic control – VLDL, TG andHDL displayed dose-dependency in the GSCM (1:1) groups. The antihyperglycaemic activities may be associated with glycosides and phenolic compoundslike coumarins which act via insulin-mimicking effect and inhibition of carbohydrate hydrolysing enzymes. in conclusion, G. sylvestre and C. micranthum aqueous leaf extracts could be relatively safe, have hypoglycaemic activities and the combination of a phenolic-rich fraction from GS and the compound 2,3,4,5-Tetrahydroxy-cyclohexane ester glucoside from CM at a dose of 10mg/kg b.w. displayed significantly synergistic hypoglycaemic effect comparing to the fractions used separately and has a better glucose-lowering effect than glibenclamide at 6mg/kg b.w. The constituents of the plants, separately and in a 1:1 combined form, could thus be beneficial in the management of diabetes mellitus.
Description
A DISSERTATION SUBMITTED TO THE SCHOOL OF POSTGRADUATE STUDIES, AHMADU BELLO UNIVERSITY, ZARIA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE AWARD OF THE DOCTOR OF PHILOSOPHY (PhD) DEGREE IN BIOCHEMISTRY DEPARTMENT OF BIOCHEMISTRY, FACULTY OF LIFE SCIENCES AHMADU BELLO UNIVERSITY, ZARIA, NIGERIA
Keywords
EVALUATION,, COMBINATION EFFECT ONTOXICITY,, ANTIDIABETIC POTENTIAL,, GYMNEMA SYLVESTRER,, COMBRETUM MICRANTHUM Fam,, LEAF EXTRACTS