Natural product vindoline stimulates insulin secretion and efficiently ameliorates glucose homeostasis in diabetic murine models

Ethnopharmacological relevance: Catharanthus roseus (L). Don (Catharanthus roseus) is a traditional antidiabetic herb widely used in many countries, and the alkaloids of Catharanthus roseus are considered to possess hypoglycemic ability. Aim of the study: To systematically investigate the potential anti-diabetic effects and the underlying antidiabetic mechanisms of vindoline, one of the alkaloids in Catharanthus roseus. Materials and methods: The regulation of vindoline against the glucose-stimulated insulin secretion (GSIS) was examined in insulinoma MIN6 cells and primary pancreatic islets. Insulin concentration was detected by Elisa assay. Diabetic models of db/db mice and type 2 diabetic rats induced by high-fat diet combining with streptozotocin (STZ/HFD-induced type 2 diabetic rats) were used to evaluate the antidiabetic effect of vindoline in vivo. Daily oral treatment with vindoline (20 mg/kg) to diabetic mice/rats for 4 weeks, body weight and blood glucose were determined every week, oral glucose tolerance test (OGTT) was performed after 4 weeks. Results: Vindoline enhanced GSIS in both glucose- and dose-dependent manners (EC50=50 mu M). It was determined that vindoline acted as a Kv2.1 inhibitor able to reduce the voltage-dependent outward potassium currents finally enhancing insulin secretion. It protected beta-cells from the cytokines-induced apoptosis following its inhibitory role in Kv2.1. Moreover, vindoline (20 mg/kg) treatment significantly improved glucose homeostasis in db/db mice and STZ/HFD-induced type 2 diabetic rats, as reflected by its functions in increasing plasma insulin concentration, protecting the pancreatic beta-cells from damage, decreasing fasting blood glucose and glycated hemoglobin (HbA(1c)), improving OGTT and reducing plasma triglyceride (TG). Conclusion: Our findings suggested that vindoline might contribute to the anti-diabetic effects of Catharanthus roseus, and this natural product may find its more applications in the improvement of beta-cell dysfunction and further the potential treatment of type 2 diabetes. (C) 2013 Elsevier Ireland Ltd. All rights reserved.