alpha-mangostin ameliorates apoptosis, inflammation and oxidative stress in cuprizone-induced demyelination in c57bl/6 mice

Introduction: alpha-mangostin (α-mg), the most abundant xanthone found in garcinia mangostana linn, has been reported to possess potent antioxidant and anti-inflammatory properties. this study aimed to investigate the neuroprotective effects of α-mg against cuprizone (cz)-induced demyelination in the corpus callosum (cc) of mice, an established animal model for multiple sclerosis (ms).methods: adult female c57bl/6 mice were fed a chow containing 0.4% (w/w) cz for 5 weeks. the animals were randomly assigned to six groups: (1) control group receiving a standard diet; (2) cz group receiving the cz-containing diet; (3–5) cz diet plus α-mg at doses of 20, 40, and 80 mg/kg/day administered via gavage; (6) standard diet plus α-mg at 80 mg/kg/day. at the end of the treatment period, levels of malondialdehyde (mda), pro-apoptotic and anti-apoptotic markers (bax, bcl-2, cleaved caspase-3), and the inflammatory cytokine tumor necrosis factor-alpha (tnf-α) were measured in the cc.results: compared with the control group, cz-treated mice exhibited significant weight loss (p<0.0001), elevated mda levels (p<0.01), an increased bax/bcl-2 ratio, enhanced cleaved caspase-3 expression (p<0.0001), and increased tnf-α levels (p<0.001). treatment with α-mg at 80 mg/kg significantly mitigated weight loss (p<0.01). furthermore, α-mg at all tested doses (20, 40, and 80 mg/kg) significantly reduced mda levels (p<0.01, p<0.001, and p<0.0001, respectively). administration of α-mg at 80 mg/kg also significantly reduced the bax/bcl-2 ratio, cleaved caspase-3 expression (p<0.0001), and tnf-α levels (p<0.0001) compared with the cz group.conclusion: these findings demonstrate that α-mg attenuates the detrimental effects of cz-induced demyelination in the cc by reducing oxidative stress, inflammation, and apoptosis.