Effects of oleanolic acid and Centella asiatica on enzymes of carbohydrate metabolism in muscle and skin of streptozotocin-induced diabetic Sprague-Dawley rats.

Abstract

Diabetes prevalence increases yearly with an expected increase to 642 million people by the year 2040. Conventional treatment of diabetes involves insulin therapy and other synthetic drugs. However, drawbacks of these forms of treatments include high cost and adverse side effects. There is therefore, a renewed focus on the use of plants and plant derived products for treatment due to their safety and limited side effects. Oleanolic acid (OA) is a plant derived triterpenoid compound that has been shown to suppress expression of genes encoding hepatic gluconeogenic enzymes and in so doing inhibits hepatic glucose production. Centella asiatica (L.) Urban (CA), an herbaceous plant belonging to the family Umbelliferae, has been traditionally used for the management of diabetes. Thus, this study was aimed at investigating the effects of OA and CA on selected enzymes of carbohydrate metabolism in muscle and skin of streptozotocin- or 10% fructose-streptozotocin-induced diabetic Sprague-Dawley rats. Non-diabetic and diabetic rats were treated with OA, 500 mg/kg of CA, 1000 mg/kg of CA and metformin over 14 days. OA increased HK and PFK activity of diabetic animals by 82% and 432% (p < 0.05) in muscle and 17.7% and 71% in skin respectively. OA also lowered FBPase activity by 24%. Similarly, 500 mg/kg of CA increased HK and PFK activity of diabetic animals by 4.4% and 624% (p < 0.05) in muscle and 11% and 35% in skin respectively. OA and CA reduced PFK expression in both muscle and skin of diabetic animals. CA also increased GS activity by 346% (p < 0.05) in skin of diabetic animals. Treatment with CA decreased ALT and AST levels and reduced damage to muscle fibre and skin epidermis of diabetic animals in histological studies. The findings of this study indicate that hypoglycaemic effect OA and CA may occur through modulation of glycolysis, gluconeogenesis and glycogen synthesis. Tissue damage and structural changes in muscle and skin caused by diabetes may be reduced by treatment with CA.