PHARMACOLOGICAL INTERACTION BETWEEN ETHANOL EXTRACT OF MORINGA OLEIFERA LEAVES AND METFORMIN IN ALLOXANINDUCED HYPERGLYCAEMIC WISTAR RATS
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Abstract
Herbs with anti-diabetic activity could initiate interactions if used concurrently with orthodox drugs. Moringa oleifera is one of such herbs usually taken as an adjunct to orthodox oral hypoglycaemic agents. This study investigated the possible pharmacological interaction between the ethanol extract of Moringa oleifera leaves (MOE) and metformin co-administered to hyperglycaemic Wistar rats and the effect of MOE on normoglycaemic rats. Hyperglycaemia was induced by administration of a single dose (150 mg/kg i.p) of alloxan. Rats having fasting blood glucose (FBG) ≥ 200 mg/dl after 72 h were considered hyperglycaemic. A dose-response study for MOE was carried out with 8 groups of hyperglycaemic rats which were administered 100, 200, 400, 800, 1000 and 2000 mg/kg MOE respectively. Blood glucose level was monitored hourly and a plot of percentage glycaemic reduction at 4h versus log dose was used to estimate the median effective dose (ED50), to be 750 mg/kg. Pharmacological interaction study was carried out for 28 days with 8 groups of hyperglycaemic rats. Group 1 served as control, groups 2, 3, and 4 received 375, 750 and 1500 mg/kg MOE corresponding to ½ ED50, ED50 and 2ED50 respectively. Groups 5, 6 and 7 received 375, 750 and 1500 mg/kg MOE but co-administered with metformin (150 mg/kg) while group 8 received metformin (150 mg/kg). For normoglycaemic rats, group 1 served as control while groups 2, 3 and 4 were administered 375, 750 and 1500 mg/kg MOE respectively. Parameters such as FBS, feed/water intake, body weight changes, lipid/protein profiles, electrolytes, creatinine and urea levels were measured in both hyperglycaemic and normoglycaemic rats. Relative organ weight (ROW) and histopathological examination of the pancreas, heart, brain, kidney, liver, lungs, spleen and stomach were also carried out. Results of the hyperglycaemic study, showed that 375mg/kg MOE significantly (p<0.05) reduced FBS on day 28, 750 and 1500 mg/kg vi MOE significantly (p<0.01) reduced FBS on days 21 and 28. The 375 and 750 mg/kg MOE co-administration with metformin produced significant (p<0.01), (p<0.001) reduction in FBS on days 14, 21 and 28 respectively while 1500 mg/kg MOE/metformin co-administration produced a significant (p<0.001) reduction in FBS on days 7, 14, 21 and 28 compared to hyperglycaemic control. A dose- dependent significant reduction in food and water intake was observed throughout the experiment with no significant change in body weight. Each of cholesterol, triglycerides and low density lipoprotein was dose-dependently reduced significantly (p<0.001) with a corresponding significant (p<0.001) increase in high density lipoprotein in all groups. Total protein and albumin were significantly (p<0.001) increased in all the groups except in the 750mg/kg MOE that showed significantly (p<0.05) increase. Serum aspartate transaminase, alanine transaminase, alkaline phosphatase and bilirubin levels reduced more significantly (p<0.001) in the extract/metformin co-administered groups. A significant (p<0.001) increase in serum Na+ , K+ and HCO3 + levels with a corresponding decrease in Cl- ions was observed at all doses when compared to the hyperglycaemic control. The MOE/metformin co-administered groups showed the most significant (p<0.001) reduction in creatinine and urea levels. Among all the organs examined, only the liver and spleen showed a dose-dependent increase in ROWs while only the pancreas showed remarkable changes in the form of beta-cell necrosis on histopathological examination. However, regeneration of beta-cells was observed in a dose-dependent fashion in all groups. The normoglycaemic study did not show any significant difference for all the parameters examined. When compared to the metformin treated group, MOE/metformin co-administration showed significant changes in all parameters monitored. In conclusion, MOE showed additive interaction with metformin. This could be important in maximizing diabetes management
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