Coumarins improved type 2 diabetes induced by high-fat diet and streptozotocin in mice via antioxidation

Coumarins extensively exist in plants and are utilized against diabetes in some folk medicines. Recent studies have demonstrated that oxidative stress plays a crucial role in the etiology and pathogenesis of diabetes mellitus. We investigated the antioxidant ability of 3 coumarins (osthole, esculin, and fraxetin) in type 2 diabetes. After being fed a high-fat diet, ICR mice were exposed to low doses of streptozotocin and then treated with experimental coumarins for 5 weeks. We found osthole, esculin, and metformin significantly lowered fasting blood glucose, HOMA-IR, and 3 blood lipids (total cholesterol, total triglyceride, free fatty acids), and increased insulin levels, while fraxetin only enhanced insulin levels and lessened free fatty acids. Both osthole and esculin had antioxidative effects in pancreas through elevating the activities of glutathione peroxidase, catalase, and superoxide dismutase; fraxetin, however, merely heightened catalase activity. By contrast, 3 coumarins significantly increased those antioxidase activities in liver. Hematoxylin and eosin staining revealed 3 coumarins, especially osthole, attenuated cellular derangement, blurry fringes of hepatic sinusoid and extensive vacuolization due to hepatocellular lipid accumulation, and lessened inflammatory infiltration in pancreas. The glomerular and islet structure of diabetic mice were improved, with reduced mesangial matrix and glomerular basement membrane thickening. Therefore, our study supports that coumarins could be promising candidates against type 2 diabetes through antioxidative mechanisms.