(-)-Leucophyllone, a Tirucallane Triterpenoid from Cornus walteri, Enhances Insulin Secretion in INS-1 Cells

Phytochemical examination of the MeOH extract from the stems and stem bark of Cornus walteri (Cornaceae) led to the isolation and verification of a tirucallane triterpenoid, (-)-leucophyllone, as a major component. Its structure was elucidated using NMR spectroscopy and liquid chromatography-mass spectrometry. The effect of (-)-leucophyllone on insulin secretion in INS-1 cells was investigated. (-)-Leucophyllone increased glucose-stimulated insulin secretion (GSIS) at concentrations showing no cytotoxic effect in rat INS-1 pancreatic β-cells. Moreover, we attempted to determine the mechanism of action of (-)-leucophyllone in the activation of insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), Akt, and pancreatic and duodenal homeobox-1 (PDX-1). Treatment of INS-1 cells with (-)-leucophyllone markedly increased the expression of these proteins. Our findings indicate the potential of (-)-leucophyllone as an antidiabetic agent.