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Nutritional Immunology

Xanthones from Mangosteen Prevent Lipopolysaccharide-Mediated Inflammation and Insulin Resistance in Primary Cultures of Human Adipocytes^1,2

³ Department of Nutrition, Mahidol University, Bangkok 10400, Thailand; ⁴ Department of Biochemistry, Mahidol University, Bangkok 10700, Thailand; ⁵ Department of Human Nutrition, The Ohio State University, Columbus, OH 43210; and ⁶ Department of Nutrition, University of North Carolina, Greensboro, NC 27402

The xanthones, - and -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 - and -MG on markers of inflammation and insulin resistance in primary cultures of newly differentiated human adipocytes treated with lipopolysaccharide (LPS). - and -MG decreased the induction by LPS of inflammatory genes, including tumor necrosis factor-, interleukin (IL)-1β, IL-6, IL-8, monocyte chemoattractant protein-1, and Toll-like receptor-2. Moreover, - and -MG attenuated LPS activation of the mitogen-activated protein kinases (MAPK) c-jun NH₂-terminal kinase, extracellular signal-related kinase, and p38. - and -MG also attenuated LPS activation of c-Jun and activator protein (AP)-1 activity. -MG was more effective than -MG on an equimolar basis. Furthermore, -MG but not -MG attenuated LPS-mediated IB- degradation and nuclear factor-B (NF-B) activity. In addition, -MG prevented the suppression by LPS of insulin-stimulated glucose uptake and PPAR- 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-B, and AP-1.

^* To whom correspondence should be addressed. E-mail: mkmcinto{at}uncg.edu.

Manuscript received 2 March 2009. Initial review completed 23 March 2009. Revision accepted 29 March 2009.

Published online 29 April 2009.