α-Mangostin: anti-inflammatory activity and metabolism by human cells

Abstract

Information about the anti-inflammatory activity and metabolism of α-mangostin (α-MG), the most abundant xanthone in mangosteen fruit, in human cells is limited. On the basis of available literature, we hypothesized that α-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. α-MG attenuated TNF-α and IL-8 secretion by the various cell lines but increased TNF-α output by both quiescent and LPS-treated MDM. The relative amounts of free and phase II metabolites of α-MG and other xanthones present in media 24 h after addition of α-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.

Figure 1

Structure of α-mangostin.

Figure 2

The lack of stability of α-MG in basal media in cell-free dishes (panel A) was offset by addition of the xanthone solubilized in DMSO to media containing 10% FBS or by addition of the xanthone incorporated in Tween 40 to basal media (panel B). Data are mean ± SD for n = 3 dishes with media.

Figure 3

α-MG attenuates secretion of inflammatory mediators in activated human cell lines but exacerbates TNF-α secretion by LPS-treated cultures of human monocyte-derived macrophages (MDM). THP-1 and MDM cells were differentiated to macrophage-like phenotype and Caco-2 cells differentiated to an enterocyte-like phenotype. Data are mean ± SD, for n ≥ 5. Different letters above bars in a panel indicate significant differences at p < 0.05.

Figure 4

Metabolism of α-MG in control and activated cell cultures. Data (mean ± SD, n ≥ 5) represent the amounts of free xanthones and their glucuronidated/sulfated metabolites in medium and cells as a percentage of the initial amount of α-MG added to each culture. Dark bars represents free xanthones and open bars indicate glucuronidated/sulfated metabolites. M: medium, C: cells, AM: apical medium, BM: basolateral medium. THP-1 and MDM cells were differentiated to macrophage-like cells and Caco-2 cells differentiated to an enterocyte-like phenotype. *Denotes statistically significant difference in free:conjugated ratio in activated cultures when compared to control cultures (p < 0.05).