Alpha-mangostin Ameliorates Apoptosis, Inflammation and Oxidative Stress in Cuprizone-induced Demyelination in C57BL/6 Mice

Introduction: Alpha-mangostin (-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 -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 -MG at doses of 20, 40, and 80 mg/kg/day administered via gavage; (6) standard diet plus -MG at 80 mg/kg/day.At the end of the treatment period, levels of malondialdehyde (MDA), proapoptotic and anti-apoptotic markers (Bax, Bcl-2, cleaved caspase-3), and the inflammatory cytokine tumor necrosis factor-alpha (TNF-) 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- levels (P<0.001).Treatment with -MG at 80 mg/kg significantly mitigated weight loss (P<0.01).Furthermore, -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 -MG at 80 mg/kg also significantly reduced the Bax/Bcl-2 ratio, cleaved caspase-3 expression (P<0.0001), and TNF- levels (P<0.0001)compared with the CZ group. Conclusion:These findings demonstrate that -MG attenuates the detrimental effects of CZinduced demyelination in the CC by reducing oxidative stress, inflammation, and apoptosis.