Inhibitory effect of xanthones isolated from the pericarp of Garcinia mangostana L. on rat basophilic leukemia RBL-2H3 cell degranulation Original Research Article

Mangostin, Garcinia mangostana L. is used as a traditional medicine in southeast Asia for inflammatory and septic ailments. Hitherto we indicated the anticancer activity induced by xanthones such as α-, β-, and γ-mangostin which were major constituents of the pericarp of mangosteen fruits. In this study, we examined the effect of xanthones on cell degranulation in rat basophilic leukemia RBL-2H3 cells. Antigen (Ag)-mediated stimulation of high affinity IgE receptor (FcεRI) activates intracellular signal transductions resulting in the release of biologically active mediators such as histamine. The release of histamine and other inflammatory mediators from mast cell or basophils is the primary event in several allergic responses. These xanthones suppressed the release of histamine from IgE-sensitized RBL-2H3 cells. In order to reveal the inhibitory mechanism of degranulation by xanthones, we examined the activation of intracellular signaling molecules such as Lyn, Syk, and PLCγs. All the xanthones tested significantly suppressed the signaling involving Syk and PLCγs. In Ag-mediated activation of FcεRI on mast cells, three major subfamilies of mitogen-activated protein kinases were activated. The xanthones decreased the level of phospho-ERKs. Furthermore, the levels of phospho-ERKs were observed to be regulated by Syk/LAT/Ras/ERK pathway rather than PKC/Raf/ERK pathway, suggesting that the inhibitory mechanism of xanthones was mainly due to suppression of the Syk/PLCγs/PKC pathway. Although intracellular free Ca2+ concentration ([Ca2+]i) was elevated by FcεRI activation, it was found that α- or γ-mangostin treatment was reduced the [Ca2+]i elevation by suppressed Ca2+ influx.