Baicalein Promotes Myelin Regeneration and Improves Motor and Cognitive Impairments in An Animal Model of Multiple Sclerosis by Mitochondrial Protection Mechanism

Qin WangZiwen WangYutong LiQiongzhang WangYanran ChenBenhao XuHaiyun Xu^*

• Wenzhou Medical University, Wenzhou, China

Background: Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease in which repetitive demyelination defeats remyelination and impairs axonal conduction thus resulting in the characteristic disabilities of MS. In searching for new drugs to treat MS, traditional Chinese herbs are gaining increasing attention. Methods: In animal experiments, an animal model of MS was established by administering cuprizone (CPZ, a copper chelator toxic to mitochondria) to C57BL/6J male mice. The therapeutic effects of baicalein (BA) were comprehensively investigated by examining its effects on the CPZ-induced neuropathological changes and behavioral abnormalities. Moreover, the cellular and molecular mechanisms underlying the therapeutic effects of BA were explored. The in vitro experiments were done with cultured oligodendrocyte (OL) lineage cells and OLN-93 cell line in the absence or presence of CPZ, H2O2, and BA. The viability, development, and mitochondrial function of the cultured cells, as well as oxidative stress measures in the cells were analyzed by means of cell biological and biochemical methods. Results: In animal experiments, BA facilitated the recovery of motor and cognitive impairment in CPZ-exposed mice while promoting the remyelination process and inhibiting neuroinflammation in their brains. Underlying these effects, BA protected brain cells of mice against the CPZ-induced decreases in mitochondrial CII, CIV, CV, and NAT8L, thereby alleviating the upregulation of NRF2 and its downstream enzymes of HO-1, NQO1, and SOD2. In the in vitro experiments, both CPZ and H2O2 inhibited the development of OL lineage cells by damaging mitochondria and resulting in oxidative stress in the cells. BA effectively prevented cultured OLs from developmental retardation by scavenging ROS resulting from damaged mitochondria. Conclusion: By demonstrating the mitochondrial protection mechanism for the protective effects of BA on CPZ-induced behavioral and neuropathological changes, this study prompts further clinical research on the application of BA in treating MS patients.