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 (MPhi) 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 MPhi (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 MPhi. 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-kappaB (NF-kappaB). In addition, alpha- and gamma-MG attenuated LPS suppression of PPARgamma gene expression in a dose-dependent manner. Notably, the ability of MPhi-conditioned media to cause inflammation and insulin resistance in primary cultures of human adipocytes was attenuated by pretreating MPhi with gamma-MG. Taken together, these data demonstrate that MG attenuates LPS-mediated inflammation in MPhi and insulin resistance in adipocytes, possibly by preventing the activation of MAPK, NF-kappaB, and AP-1, which are central to inflammatory cytokine production in WAT.
Bumrungpert
Akkarach
A
Department of Nutrition, Faculty of Public Health, Mahidol University, Bangkok, Thailand.
Kalpravidh
Ruchaneekorn W
RW
Chuang
Chia-Chi
CC
Overman
Angel
A
Martinez
Kristina
K
Kennedy
Arion
A
McIntosh
Michael
M
D017667:Adipocytes / Q000187:drug effects* / Q000473:pathology; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005260:Female; D029762:Garcinia mangostana / Q000737:chemistry*; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D007333:Insulin Resistance; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000473:pathology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D044004:Xanthones / Q000737:chemistry / Q000494:pharmacology*
C513345:AP1 peptide; D017077:Culture Media, Conditioned; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010455:Peptides; D044004:Xanthones; D020929:Mitogen-Activated Protein Kinase Kinases; C021053:mangostin