Synergistic antihyperglycemic effects between plant-derived oleanolic acid and insulin in streptozotocin-induced diabetic rats

Abstract

Studies from our laboratories indicate that Syzygium cordatum leaf extract contains triterpene mixtures [oleanolic acid (OA) and ursolic acid (UA)] with hypoglycemic properties. The aims of this study were to investigate the hypoglycemic effects of Syzygium aromaticum-derived OA and whether OA influenced the blood glucose lowering effects of insulin in streptozotocin (STZ)-induced diabetic rats. We envisaged that OA may provide a strategy with different mechanism of action for effective diabetic therapy because no single-marketed antidiabetic drug is capable of achieving long-lasting blood glucose control. The effects of various doses of OA and/or standard antidiabetic drugs on blood glucose were monitored in nondiabetic and STZ-induced diabetic rats given a glucose load after an 18-h fast. Rats treated with deionized water and standard antidiabetic drugs acted as untreated and treated positive controls, respectively. Blood glucose concentrations were measured at 15-min intervals for the first hour and hourly thereafter for 3 h. Blood glucose concentrations were also monitored in animals treated with OA and/or standard antidiabetic drugs for 5 weeks. OA like insulin decreased blood glucose concentrations in nondiabetic and STZ-induced diabetic rats. Combined OA and insulin treatment had even greater antihyperglycemic response, suggestive of a synergistic effect of the two. After 5 weeks, STZ-induced diabetic rats exhibited hyperglycemia and depleted hepatic and muscle glycogen concentrations. OA treatment lowered the blood glucose with concomitant restoration of glycogen concentrations to near normalcy. Our results suggest that OA may have a role in improving insulin sensitivity. These findings merit further research in this field.