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

Bioorg Med Chem. 2011 Nov 1;19(21):6254-60. doi: 10.1016/j.bmc.2011.09.013. Epub 2011 Sep 10.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Blotting, Western
  • Cells, Cultured
  • Enzyme Activation / drug effects
  • Fatty Acids / metabolism
  • Glucose / metabolism
  • Glycosides / chemistry
  • Glycosides / isolation & purification
  • Glycosides / pharmacology
  • Gynostemma / chemistry*
  • Mice
  • Molecular Structure
  • Muscle Fibers, Skeletal / drug effects*
  • Muscle Fibers, Skeletal / enzymology*
  • Nuclear Magnetic Resonance, Biomolecular
  • Plant Leaves / chemistry
  • RNA, Small Interfering / pharmacology
  • Saponins / isolation & purification*
  • Saponins / pharmacology*
  • Spectrophotometry, Infrared
  • Spectrophotometry, Ultraviolet
  • Triterpenes / chemistry
  • Triterpenes / isolation & purification
  • Triterpenes / pharmacology

Substances

  • Fatty Acids
  • Glycosides
  • RNA, Small Interfering
  • Saponins
  • Triterpenes
  • dammarane
  • AMP-Activated Protein Kinases
  • Glucose