EFFECTS OF CO-ADMINISTRATION OF SITAGLIPTIN AND ETHANOL LEAF EXTRACT OF MORINGA OLEIFERA LAM. IN ALLOXAN-INDUCED DIABETES MELLITUS AND ITS CHRONIC COMPLICATIONS IN RATS

EFFECTS OF CO-ADMINISTRATION OF SITAGLIPTIN AND ETHANOL LEAF EXTRACT OF MORINGA OLEIFERA LAM. IN ALLOXAN-INDUCED DIABETES MELLITUS AND ITS CHRONIC COMPLICATIONS IN RATS

Abstract:

Incidence and prevalence of type 2 diabetes mellitus (T2DM), with its resultant complications continue to be on the increase. The outcome of management is highly dependent on efficacy, safety and suitability of medicines used concomitantly. An aspect of efficacy/safety that is of growing importance is that of drug-herb interactions. The co-administration of Sitagliptin, an antidiabetic agent and Moringa oleifera, a herb traditionally used in the management of T2DM is a real possibility in the diabetic population. This study investigated the effects of co-administration of Sitagliptin (50 mg/kg) and ethanol leaf extract of M. oleifera (300 mg/kg) on the onset, progression and amelioration of diabetic complications in alloxan-induced diabetic rats. Six groups of eight rats per group were used, with groups I and II as normal (NC) and diabetic controls (DC). Groups III to VI were diabetic rats treated with Sitagliptin (III), M. oleifera (IV), Sitagliptin and M. oleifera (SM) (V), in two phases of 28 days and 42 days respectively, with 2 weeks delayed treatment in a post prandial hyperglycaemic group (VI). Antihyperglycaemic efficacy of the drug and extract using fasting blood glucose (FBG), random blood glucose (RBG) and insulin (INS) levels were determined. Inflammatory, cardioactive and oxidative stress markers in addition to lipid profiles were investigated to ascertain effects on diabetic cardiomyopathy and macroangiopathy. Morphological and functional markers of the kidneys, eyes and pain perception using (hyperalgesic and allodynia) models were also investigated for the effects of the combination on microvascular complications. There was significant decrease in FBG (p<0.01) from day 14 (56%) to day 42 (55%) and in RBG (p<0.01) on day 42 (27%) compared to day 1 in rats treated with only Sitagliptin. In rats treated with only M. oleifera, significant decrease (45%) was observed in FBG (p<0.01) on day 21 compared to day 1, thereafter, there was an increase in FBG from day 28 (29%) up to day 42 (65%) compared to day 21. The co-administration of the drug and extract, however showed significant decrease in FBG (p<0.01) from day 14(60%) to day 28 (38%) compared to day 1, after which there was a steady increase of up to 57% on day 42 compared to day 28. There was also a significant decrease in RBG (p<0.001) in SM group on day 42 (24%) compared to day 1. Body weights did not differ significantly in any of the groups for the entire period of the study. No significant difference was seen in mean serum levels of INS, xxi adiponectin (ADP) and C reactive proteins (CRP) comparing the combination group to DC in both phases. There was a significant decrease (p<0.005) in serum tissue necrosis factor alpha (TNFα), and non significant decrease (21%) in mean serum levels of B type natriuretic peptide (BNP) in SM group, following 28 days administration, but with 11% increase after 42 days compared to DC. A significant increase (p<0.05), in serum levels of catalase (CAT) on day 28, and non significant increase on day 42, in SM group compared to the individual agents. Also, a non significant decrease in serum levels of malondialdehyde (MDA) in SM group after 28 days, compared to diabetic control, with no effect seen on day 42. There was a significant increase in triglyceride (TG) levels (p<0.05) compared to diabetic control, with no effect on high density lipoprotein (HDL), total cholesterol (TC) and low density lipoprotein (LDL) levels except decreases in TC and LDL in post prandial treated groups. No significant histopathological findings in sections of the aorta in the SM group compared to aortic vasculitis and thickening seen in DC. Sections of heart in SM group showed congested myofibrils (though no significant difference in relative heart weight). No significant difference were observed in serum urea, albumin and liver enzyme levels in SM group compared to DC and the individual agents, but significant increase in relative kidney weight (p<0.001) compared to NC. There was however, no significant amelioration of kidney necrosis compared to DC. There was a significant increase (p<0.05) in pain threshold (thermal and mechanical) in the 5th week in SM group, compared to week 2, but with a further decrease in the 6th week. Sections of the foot pad of rat treated with SM showed moderate intraepidemal nerve fibre density. Evidence of mild lenticular opacity was observed, with no significant effect in pathologic lesions in the retina. M. oleifera decreased antihyperglycaemic effect of Sitagliptin with slight delay in the onset and progression, without ameliorating chronic complications in diabetic rats. However prolonged administration showed negative effects on biomarkers of diabetic cardiomyopathy and nephropathy. Caution should therefore be exercised on chronic and indiscriminate use of M. oleifera alongside Sitagliptin.

EFFECTS OF CO-ADMINISTRATION OF SITAGLIPTIN AND ETHANOL LEAF EXTRACT OF MORINGA OLEIFERA LAM. IN ALLOXAN-INDUCED DIABETES MELLITUS AND ITS CHRONIC COMPLICATIONS IN RATS

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