Baicalein Improves Motor and Cognitive Impairment While Promoting Remyelination in Cuprizone-Exposed Mice Through Antioxidant Mechanism

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease. Repetitive demyelination defeats remyelination and impairs axonal conduction thus resulting in the characteristic disabilities of MS. Therefore, reducing demyelination and promoting remyelination are key strategies for the prevention and treatment of MS. In searching for new drugs to treat MS, many traditional Chinese herbs are gaining increasing attention. In the present study, baicalein (BA) was comprehensively investigated, by examining its effects on the cuprizone (CPZ)-induced neuropathological changes and behavioral abnormalities which are reminiscent of the clinical symptoms of MS patients, and exploring the cellular and molecular mechanisms underlying the effects. Our in vivo experiments demonstrated that BA facilitates the recovery of motor and cognitive impairment in CPZ-exposed mice while promoting the remyelination process and inhibiting neuroinflammation in their brains. Underlying these protective effects, BA intervention prevented the nuclear factor erythroid 2-related factor 2 (NRF2) and its downstream antioxidant enzymes (HO-1, NQO1, and SOD2) from over activation, thereby maintaining the signal pathway at normal levels through its antioxidant actions. Our in vitro experiments provided evidence that both CPZ and H2O2 delay the development of oligodendrocyte (OL) lineage cells by damaging mitochondria of the cells and resulting in oxidative stress. In the absence of astrocytes and microglia, BA effectively prevented cultured OLs from development delay by scavenging ROS resulted from damaged mitochondria of the cells. The elucidation of these cellular and molecular mechanisms will prompt clinical application of more naturally derived compounds with antioxidant properties to treat patients with MS.