Hypolipidaemic and insulin secretagogue activities of (R)-(−)-carvone

Abstract

Background: Dyslipidaemias are common in patients with diabetes mellitus. A high prevalence of type 2 diabetes in hyperlipidaemic patients also exists. The aim of this study was to find a treatment that lowers both blood glucose and lipid levels simultaneously. Methods: The hypolipidaemic effect of (R)-(−)-carvone was investigated in a tyloxapol-induced hyperlipidaemia mice model. Furthermore, its effect on insulin secretion and proliferation of 1.1E7 human pancreatic β-cells was studied. In addition, using molecular docking, the binding affinity of (R)-(−)-carvone against 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase was estimated. Results: (R)-(−)-carvone (100 mg/kg) decreased plasma triglyceride, total cholesterol, low-density lipoprotein cholesterol (LDL-C) levels and atherogenic index by 90.6%, 49.3%, 56.6% and 70.3%, respectively, but it had no effect on high-density lipoprotein cholesterol (HDL-C). Furthermore, it increased hepatic triglyceride level and catalase activity by 79.6% and 59.6%, respectively. In-vitro, 500 µM (R)-(−)-carvone increased insulin secretion by 454.4% and proliferation of 1.1E7 cells with no cytotoxic effects up to a concentration of 100 µM. Molecular docking simulation demonstrated a good binding affinity with –5.03 Kcal/mol of (R)-(−)-carvone to HMG-CoA reductase. Conclusion: The hypolipidaemic effect of (R)-(−)-carvone is comparable to that of fenofibrate. (R)-(−)-carvone has the advantage over fenofibrate of not producing hypoglycaemia in animals. Furthermore, (R)-(−)-carvone increased proliferation and insulin secretion of human pancreatic β-cells.