Xanthones from mangosteen prevent lipopolysaccharide-mediated inflammation and insulin resistance in primary cultures of human adipocytes

J Nutr. 2009 Jun;139(6):1185-91. doi: 10.3945/jn.109.106617. Epub 2009 Apr 29.

Abstract

The xanthones, alpha- and gamma-mangostin (MG), are major bioactive compounds found in mangosteen and are reported to have antiinflammatory properties in several murine models. Given the association between obesity, chronic low-grade inflammation, and insulin resistance, we examined the effects of alpha- and gamma-MG on markers of inflammation and insulin resistance in primary cultures of newly differentiated human adipocytes treated with lipopolysaccharide (LPS). alpha- and gamma-MG decreased the induction by LPS of inflammatory genes, including tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-8, monocyte chemoattractant protein-1, and Toll-like receptor-2. Moreover, alpha- and gamma-MG attenuated LPS activation of the mitogen-activated protein kinases (MAPK) c-jun NH(2)-terminal kinase, extracellular signal-related kinase, and p38. alpha- and gamma-MG also attenuated LPS activation of c-Jun and activator protein (AP)-1 activity. gamma-MG was more effective than alpha-MG on an equimolar basis. Furthermore, gamma-MG but not alpha-MG attenuated LPS-mediated IkappaB-alpha degradation and nuclear factor-kappaB (NF-kappaB) activity. In addition, gamma-MG prevented the suppression by LPS of insulin-stimulated glucose uptake and PPAR-gamma and adiponectin gene expression. Taken together, these data demonstrate that MG attenuates LPS-mediated inflammation and insulin resistance in human adipocytes, possibly by inhibiting the activation of MAPK, NF-kappaB, and AP-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Adult
  • Cells, Cultured
  • Female
  • Garcinia mangostana / chemistry*
  • Gene Expression / drug effects
  • Humans
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / prevention & control*
  • Insulin Resistance / physiology*
  • Lipopolysaccharides / toxicity
  • Middle Aged
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • RNA, Messenger / metabolism
  • Transcription Factor AP-1 / genetics
  • Transcription Factor AP-1 / metabolism
  • Transfection
  • Xanthones / chemistry
  • Xanthones / pharmacology*
  • Young Adult

Substances

  • Lipopolysaccharides
  • NF-kappa B
  • RNA, Messenger
  • Transcription Factor AP-1
  • Xanthones
  • gamma-mangostin
  • Mitogen-Activated Protein Kinase Kinases
  • mangostin