alpha-Mangostin: Anti-Inflammatory Activity and Metabolism by Human Cells

Information about the anti-inflammatory activity and metabolism of alpha-mangostin (alpha-MG), the most abundant xanthone in mangosteen fruit, in human cells is limited. On the basis of available literature, we hypothesized that alpha-MG will inhibit the secretion of pro-inflammatory mediators by control and activated macrophage-like THP-1, hepatic HepG2, enterocyte-like Caco-2, and colon HT-29 human cell lines, as well as primary human monocyte-derived macrophages (MDM), and that such activity would be influenced by the extent of metabolism of the xanthone. alpha-MG attenuated TNF-alpha and IL-8 secretion by the various cell lines but increased TNF-alpha output by both quiescent and LPS-treated MDM. The relative amounts of free and phase II metabolites of alpha-MG and other xanthones present in media 24 h after addition of alpha-MG was shown to vary by cell type and inflammatory insult. Increased transport of xanthones and their metabolites across Caco-2 cell monolayers suggests enhanced absorption during an inflammatory episode. The anti-inflammatory activities of xanthones and their metabolites in different tissues merit consideration.