Acanthopanax senticosus extract (ASE), a dietary supplement with antifatigue, neuroprotective, and immunomodulatory properties, has been widely used due to its high
polyphenol content. Our previous study showed that ASE could be used to treat
Parkinson's disease (PD) as it contains multiple
monoamine oxidase B inhibitors prescribed in early PD. However, its mechanism remains ambiguous. In this study, we investigated the protective effects of ASE on
MPTP-induced PD in mice and explored the underlying mechanisms of action. We found that the administration of ASE significantly improved motor coordination in mice with
MPTP-induced PD. As shown by quantitative proteomic analysis, 128
proteins' expression significantly changed in response to ASE administration, most of which were involved with Fcγ receptor-mediated phagocytosis in macrophages and monocytes signaling pathway, PI3K/AKT signaling pathway, and
insulin receptor signaling pathway. Furthermore, the network analysis results showed that ASE modulates
protein networks involved in regulating cellular assembly, lipid metabolism, and morphogenesis, all of which have implications for treating PD. Overall, ASE served as a potential therapeutic because it regulated multiple targets to improve motor deficits, which could lay the strong foundation for developing anti-PD dietary supplements.