Xanthones from Mangosteen Inhibit Inflammation in Human Macrophages and in Human Adipocytes Exposed to Macrophage-Conditioned Media

Obesity-associated inflammation is characterized by recruitment of macrophages (M Phi) into white adipose tissue (WAT) and production of inflammatory cytokines, leading to the development of insulin resistance. The xanthones, alpha- and gamma-mangostin (MG), are major bioactive compounds found in mangosteen that are reported to have antiinflammatory and antioxidant properties. Thus, we examined the efficacy of MG to prevent lipopolysaccharide (LPS)-mediated inflammation in human M Phi (differentiated U937 cells) and cross-talk with primary cultures of newly differentiated human adipocytes. We found that alpha- and gamma-MG attenuated LPS-induced expression of inflammatory genes, including tumor necrosis factor-alpha, interleukin-6, and interferon gamma-inducible protein-10 in a dose-dependent manner in MO. We also found that alpha- and gamma-MG attenuated LPS-activated mitogen-activated protein kinases (MAPK) and activator protein (AP)-1, but only gamma-MG reduced nuclear factor-kappa B (NF-kappa B). In addition, alpha- and gamma-MG attenuated LPS suppression of PPAR gamma gene expression in a close-dependent manner. Notably, the ability of M Phi-conditioned media to cause inflammation and insulin resistance in primary cultures of human adipocytes was attenuated by pretreating M Phi with gamma-MG. Taken together, these data demonstrate that MG attenuates LPS-mediated inflammation in M Phi and insulin resistance in adipocytes, possibly by preventing the activation of MAPK, NF-kappa B, and AP-1, which are central to inflammatory cytokine production in WAT. J. Nutr. 140: 842-847, 2010.