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 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), proapoptotic 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.