Integrated proteomics and metabolomics reveals metabolism disorders in the α-syn mice and potential therapeutic effect of Acanthopanax senticosus extracts

Abstract

Ethnopharmacological relevance: Acanthopanax senticosus (Rupr.et.Maxim.)Harms(AS) is an extract of Eleutherococcus senticocus Maxim(Rupr.et.Maxim.). In modern medical interpretation, Acanthopanax senticosus can be used to treat Parkinson's disease, and a large number of modern pharmacological and clinical studies also support this application. Our study demonstrated that AS extracts can increase the activity of various antioxidant enzymes and improve the symptoms of Parkinson's disease in mice.

Aim of the study: The current study looked at the protective effect of Acanthopanax senticosus extracts(ASE) in preventing PD.

Methods and materials: First, the α-syn-overexpressing mice were chosen as suitable models for Parkinson's disease in vivo. HE staining was used to observe the pathological changes in the substantia nigra. Meanwhile, TH expression in substantia nigra was analyzed by immunohistochemistry. Behavioral and biochemical tests evaluated neuroprotective effects of ASE on PD mice. Subsequently, combined with proteomics and metabolomics analysis, the changes in brain proteins and metabolites in mice treated with ASE for PD were studied. Finally, Western blot was used to detect metabolome-related and proteomic proteins in the brain tissue of α-syn mice.

Results: Forty-nine common differentially expressed proteins were screened by proteomics analysis, among which 28 were significantly up-regulated,and 21 were significantly down-regulated. Metabolomics analysis showed that twenty-five potentially important metabolites were involved in the therapeutic effect of ASE on PD. Most of the different proteins and metabolites were considered to be enriched in a variety of species in metabolic pathways, including glutathione metabolism and alanine aspartate and glutamate metabolism and other pathways, which means that ASE may have molecular mechanisms to ameliorate PD dysfunction. In addition, we found that decreases in glutathione and glutathione disulfide levels may play a critical role in these systemic changes and warrant further investigation. In the glutathione metabolic pathway, ASE also acts on GPX4, GCLC and GCLM.

Conclusions: ASE can effectively relieve behavioral symptoms of α-syn mice and relieve oxidative stress in brain tissue. These findings suggest that ASE offers a potential solution to target these pathways for the treatment of PD.

Keywords: Acanthopanax senticosus; Metabolomics; Oxidative stress; Parkinson's disease; Proteomics; α-synuclein.