Abstract:
Gradual worsening of type 2 diabetes mellitus is accompanied by progressive deterioration in β cell function and a reduction in the β cell mass. β cells are vulnerable to excess reactive oxygen species (ROS) because of their inherently low expression of antioxidant enzymes. Protection of β cells would provide a valuable approach to treating type 2 diabetes. Madecassoside, is a triterpenoid antioxidant with anti-inflammatory, myocardial-, renal- and neuro-protective effects. This study tests the hypothesis that madecassoside reduces the elevated blood glucose in experimental diabetes by protecting the β-cells. In in vivo study, diabetes was induced in overnight-fasted Sprague-Dawley rats using streptozotocin (60 mg/kg, i.v.) followed by nicotinamide (210 mg/kg, i.p.). Madecassoside (50 mg/kg) was administered orally daily for four weeks. Biochemical parameters such as fasting blood glucose, plasma insulin, HbA1c, liver and lipid parameters were measured, along with enzymatic and nonenzymatic activities, lipid peroxidation, histological
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and immunohistochemical studies. Rat insulinoma (INS-1E) cells was treated with madecassoside (10, 30, 60 μM) in the presence of high glucose (HG), hydrogen peroxide (H2O2), a cytokine cocktail (IL-1β, IFNγ and TNFα) or streptozotocin (STZ). Reactive oxygen species (ROS) measurement and apoptosis studies were also carried out in vitro. Madecassoside potentially normalized the elevated fasting blood glucose levels by increasing plasma insulin concentration, alleviated oxidative stress by improving enzymatic antioxidants and reducing lipid peroxidation in treated diabetic rats. Histopathological examination of the pancreas of madecassoside treated rats showed significant recovery of islet structural degeneration and also increased in area of islets compared to diabetic rats. Increased insulin granules in madecassoside treated rats as evidenced by the immunohistochemical study and improved expressions of GLUT4 also reflects the protective role of madecassoside. Furthermore, in in vitro studies, madecassoside showed non-cytotoxic effect on INS-1E cells, while reversing significant reduction of cell viability caused by HG, cytokine cocktail, H2O2 and STZ. Madecassoside also concentration-dependently reduced ROS production by INS-1E cells in response to these agents. Interestingly, the results demonstrate madecassoside’s capability in protecting the β-cells in vivo and in vitro. Thus, madecassoside may be useful in preserving the β-cells and managing type-2 diabetes mellitus.
