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 anti-diabetic 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 anti-diabetic 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 anti-diabetic effect of vindoline in vivo. Daily oral treatment with vindoline (20mg/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 μM). 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 β-cells from the cytokines-induced apoptosis following its inhibitory role in Kv2.1. Moreover, vindoline (20mg/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 β-cells from damage, decreasing fasting blood glucose and glycated hemoglobin (HbA1c), 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 β-cell dysfunction and further the potential treatment of type 2 diabetes.