In Vitro: alpha-Mangostin (α-Mangostin) exhibits a selective inhibitory effect on IDH1-R132H, but not on IDH1. alpha-Mangostin (α-Mangostin) competitively inhibits the binding of alpha-mangostin (α-KG) to IDH1-R132H. The structure–relationship study reveals that alpha-Mangostin (α-Mangostin) exhibits the strongest core inhibitor structure. alpha-Mangostin (α-Mangostin) selectively promotes demethylation of 5-methylcytosine (5mC) and histone H3 trimethylated lysine residues in IDH1 (+/R132H) MCF10A cells. Cell proliferation significantly decreases in a dose-dependent manner in the cells treated with alpha-mangostin. Alpha-mangostin also increases the levels of Bax (pro-apoptotic), cleaved caspase-3, cleaved caspase-9 and cleaved-poly(ADP-ribose) polymerase (PARP). alpha-Mangostin (α-Mangostin) significantly inhibits light-induced degeneration of photoreceptors and 200 μM H2O2-induced apoptosis of RPE cells. 200 μM H2O2-induced generation of reactive oxygen species (ROS) and light-induced generation of malondialdehyde (MDA) are suppressed by alpha-Mangostin (α-Mangostin).
In Vivo: alpha-Mangostin (α-Mangostin) reduces risk of liver fibrosis through the decrease in p53 expression as compared to the TAA_DMSO treatment. The serum levels of the liver enzymes AST and ALT after treatment with α-mangostin decrease as compared to DMSO alone.