Positive interaction of mangiferin with selected oral hypoglycemic drugs: a therapeutic strategy to alleviate diabetic nephropathy in experimental rats.

Diabetic nephropathy (DN) is one of the notorious diabetes associated complications. Despite many therapeutic strategies available, metabolic control of DN continues to poses a challenge. In this study, the interactions of mangiferin with selected oral hypoglycemic drugs, metformin and gliclazide to effectively alleviate the symptoms of renal injury in DN are evaluated. Male Sprague Dawley rats were used as experimental model and type II diabetes was induced by administration of high fat diet and low dose streptozotocin. Oral intervention of mangiferin with metformin and gliclazide for a period of 28 days was given to diabetic rats. At the end of the treatment period, biochemical parameters, kidney function markers, anti-oxidant enzymes levels, oxidative stress mediated gene expression and histology were analysed. Significant reduction in the serum biochemical markers (glucose, urea and creatinine) were observed in the groups treated with combination drugs. Marked improvement in the combination treated groups in terms of inflammation and oxidative damage in the gene (TNFα, NFκB, TGFß, VEGF, PKC) and protein expression (NFκB, VEGF) were noted in the kidney tissue alleviating the symptoms of DN. These results were further corroborated with histopathological results. Scientific data in the present study reveals that the combinations of mangiferin with the oral hypoglycemic drugs have been favorable in alleviating renal injury. Hence, a combination therapy to alleviate the vascular complication, diabetic nephropathy may be considered as a possible therapeutic strategy by including natural phytocompounds as an add on therapy to conventional oral hypoglycemic drugs.

Antidiabetic effect of mangiferin in combination with oral hypoglycemic agents metformin and gliclazide.

BACKGROUND: Diabetes mellitus poses serious threat to the global population due to the alarming diabetic complications it leads to. The current therapeutic options available can be improved for better efficiency and maximum benefits. Combination therapy has been commonly used to improve the efficacy and to minimize the side effects of drugs in current clinical use. PURPOSE: The present study aims to assess the interaction between a natural molecule mangiferin with the commercially available oral hypoglycemic drugs metformin and gliclazide in diabetic rats. METHODS: In this study, the in vitro cytotoxicity and glucose uptake studies were performed in HepG2 cells. Based on experimental data, the combination index of the hypoglycemic drugs like metformin and gliclazide in combination with different doses of mangiferin was determined using COMPUSYN software. Further, in vivo studies were performed in HFD + STZ induced diabetic male Sprague Dawley rats. Serum parameters, enzyme markers, hepatic oxidative stress markers, gene and protein expression studies and histopathological analyses were performed in rat liver to identify the mode of action of the combination drug administration. RESULTS: The in vitro studies on HepG2 cells suggest a positive interaction of mangiferin with both metformin and gliclazide at specific concentrations as evidenced by glucose uptake. The hepatic enzymes, oxidative stress markers, carbohydrate metabolizing enzymes, gene (AMPK, Akt, ACC ß and Glut-2) and protein (PPARα, PPARγ) expression confirmed the results of the in vitro studies. Both the combinations of mangiferin with metformin and mangiferin with gliclazide exhibited potent antidiabetic effect. The combination of mangiferin with metformin was insulin dependent (Akt pathway) whereas the combination of mangiferin and gliclazide was insulin independent (AMPK pathway). CONCLUSION: The overall results suggest that combination of mangiferin with both metformin and gliclazide alleviates diabetic conditions potentially at specific doses and modulates the adverse effect of high dose of commonly used OHD's. This combination therapy can be translated for its clinical use as a diabetes management strategy.