Xanthones from mangosteen prevent lipopolysaccharide-mediated inflammation and insulin resistance in primary cultures of human adipocytes.
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.
Bumrungpert
Akkarach
A
Department of Nutrition, Mahidol University, Bangkok 10400, Thailand.
Kalpravidh
Ruchaneekorn W
RW
Chitchumroonchokchai
Chureeporn
C
Chuang
Chia-Chi
CC
West
Tiffany
T
Kennedy
Arion
A
McIntosh
Michael
M
D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000328:Adult; D002478:Cells, Cultured; D005260:Female; D029762:Garcinia mangostana / Q000737:chemistry*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D007333:Insulin Resistance / Q000502:physiology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008875:Middle Aged; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D044004:Xanthones / Q000737:chemistry / Q000494:pharmacology*; D055815:Young Adult
D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D044004:Xanthones; D020929:Mitogen-Activated Protein Kinase Kinases; C021053:mangostin