Effects of Centella asiatica on skeletal muscle structure and key enzymes of glucose and glycogen metabolism in type 2 diabetic rats

Background: Dysregulation of glucose and glycogen metabolism are crucial mechanisms implicated in type 2 diabetes mellitus (T2DM). Centella asiatica (L.) Urban (Apiaceae) has been utilized as a traditional medicine in Africa and Asia for centuries and is commercially available as a dietary supplement. Aim: We explored for the first time, the possible efficacy of Centella asiatica (CA) extract in ameliorating T2DM-induced changes in key enzymes involved in glucose and glycogen metabolism in the rat skeletal muscle. Methods: Diabetic rats were orally treated with vehicle, CA (500 and 1000 mg/kg) or metformin (300 mg/kg) daily for 14 days. Skeletal muscle activities of hexokinase (HK), phosphofructokinase (PFK) and fructose 1,6-bisphosphatase (FBPase) were determined by spectrophotometric assays while those of glycogen synthase (GS) and glycogen phosphorylase (GP) were assayed radio-chemically. Histological examination of skeletal muscle was also performed. Results: Rats with induced T2DM had reduced activities of HK (25%), PFK (88%), and GS (38%) when compared to non-diabetic rats. Treatment of diabetic rats with CA500 increased the activities of PFK (7-fold), and FBPase (23%). Further, treatment of diabetic rats with CA1000 also increased the activities of GS (27%) and GP (50%) with little change in these parameters for diabetic rats treated with CA500. These effects probably led to the reduced blood glucose level and elevated skeletal muscle glycogen content observed in CA-treated rats relative to diabetic controls. Furthermore, CA treated rats had reduced the morphological damage of skeletal muscle fibres compared to the non-treated diabetic control rats. Conclusion: Our findings strongly suggest that the anti-diabetic effects of CA in part target muscle glucose and glycogen metabolism and hence supporting its folkloric medical use as an anti-diabetic remedy.