Multiple sclerosis (MS) is an autoimmune-mediated degenerative disease of the central nervous system (CNS) characterized by immune cell infiltration, demyelination and axonal injury. Oxidative stress-induced inflammatory response, especially the destructive effect of immune cell-derived free radicals on neurons and oligodendrocytes, is crucial in the onset and progression of MS. Therefore, targeting oxidative stress-related processes may be a promising preventive and therapeutic strategy for MS. Animal models, especially rodent models, can be used to explore the in vivo molecular mechanisms of MS considering their similarity to the pathological processes and clinical signs of MS in humans and the significant oxidative damage observed within their CNS. Consequently, these models have been used widely in pre-clinical studies of oxidative stress in MS. To date, many natural products have been shown to exert antioxidant effects to attenuate the CNS damage in animal models of MS. This review summarized several common rodent models of MS and their association with oxidative stress. In addition, this review provides a comprehensive and concise overview of previously reported natural antioxidant products in inhibiting the progression of MS.

Background/Aims. Multiple sclerosis (MS) and neuromyelitis optica (NMO) are the most common autoimmune demyelinating diseases of the central nervous system (CNS), with some similar pathological and clinical features. Bu-Shen-Yi-Sui (BSYS) Capsule, a Chinese herbal prescription, has been shown to be a potential therapeutic agent for MS and NMO. However, its antidemyelination mechanism in inflammatory demyelinating diseases of the CNS has not been fully clarified. This study is aimed at exploring the key components and potential mechanism of BSYS in the treatment of CNS demyelinating disease (CNSD) based on network pharmacology. Methods. The potential active ingredients and corresponding potential targets of BSYS Capsule were obtained from the TCMSP, BATMAN-TCM, Swiss Target Prediction platform, and literature research. Disease targets of CNSD were explored through the GeneCards and the DisGeNET databases. The matching targets of BSYS in CNSD were identified from a Venn diagram. The protein-protein interaction (PPI) network was constructed using bioinformatics methods. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to predict the mechanisms of BSYS. Furthermore, the neuroprotective effects of BSYS were evaluated using a cell model of hydrogen peroxide- (H₂O₂-) induced cell death in OLN-93 cells. Results. A total of 59 potential bioactive components of BSYS Capsule and 227 intersection targets were obtained. Topological analysis showed that AKT had the highest connectivity degrees in the PPI network. Enrichment analysis revealed that the targets of BSYS in the treatment of CNSD were the PI3K-Akt and MAPK signaling pathway, among other pathways. GO analysis results showed that the targets were associated with various biological processes, including apoptosis, reactive oxygen species metabolic process, and response to oxidative stress, among others. The experimental results demonstrated that BSYS drug-containing serum alleviated the H₂O₂-induced increase in LDH, MDA, and ROS levels and reversed the decrease in SOD and mitochondrial membrane potential induced by H₂O₂. BSYS treatment also decreased the number of TUNEL (+) cells, downregulated Bcl-2 expression, and upregulated Bax and c-caspase-3 expression by promoting Akt phosphorylation. Conclusion. BSYS Capsule alleviated H₂O₂-induced OLN-93 cell injury by increasing Akt phosphorylation to suppress oxidative stress and cell apoptosis. Therefore, BSYS can be potentially used for CNSD treatment. However, the results of this study are only derived from in vitro experiments, lacking the validation of in vivo animal models, which is a limitation of our study. We will further verify the underlying mechanisms of BSYS in animal experiments in the future.