Insulinotropic and antidiabetic properties of Eucalyptus citriodora leaves and isolation of bioactive phytomolecules

Abstract

Abstract Objective The aim of this study was to delineate the mechanisms of action of the plant Eucalyptus citriodora used traditionally for the treatment of type 2 diabetes. Methods Insulin secretion and signal transduction were measured using clonal pancreatic β-cells and mouse islets. Glucose uptake was assessed using 3T3-L1 adipocytes and in vitro systems assessed additional glucose-lowering actions. High-fat-fed (HFF) obese rats were used for in vivo evaluation and phytoconstituents were identified by RP-HPLC followed by LC-MS. Key findings Eucalyptus citriodora stimulated 1.2–4.6-fold insulin release that was inhibited by the Ca2+-channel blocker, verapamil, KATP-channel opener, diazoxide and Ca2+ free conditions. The effect was potentiated by IBMX and preserved in presence of tolbutamide or 30 mM KCl. The action mechanism involved membrane depolarization and elevation of intracellular Ca2+. Eucalyptus citriodora also significantly increased glucose uptake by 3T3-L1 cells and inhibited digestion of starch, glucose absorption, DPP-IV enzyme and glycation of protein. Administration of E. citriodora (250 mg/5 ml/kg) for 9 days to HFF obese-diabetic rats improved glycaemic control and β-cell function. The isolated phytoconstituents responsible for the β-cell actions included quercitrin, isoquercitrin and rhodomyrtosone E. Conclusions Eucalyptus citriodora improves glycaemic control via multiple mechanisms. Further studies are required to assess the utility of the plant or active constituents in the therapy of type 2 diabetes.