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

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.