New dammarane-type glucosides as potential activators of AMP-activated protein kinase (AMPK) from Gynostemma pentaphyllum

Abstract

AMP-activated protein kinase (AMPK) is a key sensor and regulator of glucose, lipid, and energy metabolism throughout the body. Activation of AMPK improves metabolic abnormalities associated with metabolic diseases including obesity and type-2 diabetes. The oriental traditional medicinal herbal plant, Gynostemma pentaphyllum, has shown a wide range of beneficial effects on glucose and lipid metabolism. In this study, we found that G. pentaphyllum contains two novel dammarane-type saponins designated as damulin A (1), 2α,3β,12β–trihydroxydammar-20(22)-E,24-diene-3-O-[β-d-glucopyranosyl-(1→2)-β-d-glucopyranoside], and damulin B (2), 2α,3β,12β-trihydroxydammar-20,24-diene-3-O-[β-d-glucopyranosyl-(1→2)-β-d-glucopyranoside], that strongly activate AMPK in cultured L6 myotube cells. Damulins A and B also increased β-oxidation and glucose uptake with increasing GluT4 translocation to the plasma membrane in L6 myotube cells. Taken together our results indicate that activation of AMPK by damulins A and B may contribute to beneficial effect of G. pentaphyllum on glucose and lipid metabolism.