Dietary supplementation of Acanthopanax senticosus extract alleviates motor deficits in MPTP-induced Parkinson's disease mice and its underlying mechanism

Abstract

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.

Keywords: Acanthopanax senticosus extract; MPTP; Parkinson’s disease; proteomics; signaling pathway; therapeutic mechanism.

FIGURE 1

(A) The chemical composition of ASE identified by UPLC-ESI-Q-TOF-MS/MS analysis in negative ion mode. (B) MS/MS spectrum of Syringaresinol-4-O-β-D-glucoside.

FIGURE 2

ASE treatment alleviates motor deficits in MPTP-induced Parkinson’s disease mice. (A) the spontaneous activity test; (B) the rotarod test; (C) the pole-climbing test; (D) the hanging test. The data are presented as the means ± SDs of 15 biological replicates (###p < 0.01, compared with the control group; ^***p < 0.05, compared with the model group).

FIGURE 3

(A) Volcano plot analysis of the differentially expressed proteins between the ASE treatment and the PD group. Proteins that have a difference of fold change > 1.2 or < −1.2 and a P < 0.05 are defined as significantly different. The red points indicate proteins with a significant upregulation, while the green points indicate proteins with a significant downregulation. (B) Heatmap analysis of the differentially expressed proteins between the ASE treatment and the PD group.

FIGURE 4

Gene Ontology functional annotations and KEGG pathway analysis of ASE in treating PD. The radius of the circle indicates the number of genes enriched, while the color indicates the number of p-values.

FIGURE 5

(A) The highest ranked canonical IPA pathways of the differentially expressed proteins. The horizontal axis shows the pathway name and the vertical axis is the p-value of each pathway. (B) The top protein-protein interaction network responding to ASE treatment for PD was predicted by IPA. Twenty-six proteins are involved in this network. The symbols labeled in red and green represent up-regulation and down-regulation, respectively.