Integrated Brain Metabolomics and Network Pharmacology Analysis to Reveal the Improvement Effect of Bai Chan Ting on Parkinson’s Disease

Abstract

Background. Baichanting (BCT),a traditional Chinese medicine prescription, is a combination of Acanthopanax senticosus, Paeonia lactiflora, and Uncaria three herbs, which has the effect of benefiting the kidney and calming the liver. The study was aimed at investigating the protective effect of BCT against Parkinson’s disease using an integrated strategy of network pharmacology and brain metabolomics. Materials and Methods. By integrating network pharmacology with metabolomic research, the protective effect of BCT against PD was investigated using a transgenic mouse model for α-synuclein. The metabolite level and gene level components of BCT that might be anti-PD were separated out. Indicators of behavior and pharmacodynamics were employed to gauge the effectiveness of BCT on PD in the preliminary stages. Network pharmacology, which may be the target of BCT, screened the active substances and target genes. The use of metabolomics to identify potential biomarkers of PD, and then through network pharmacology and metabolic pathways to determine their regulatory enzymes and regulatory genes, improve the pathway mechanism of the disease, has important guiding significance for the in-depth study of the pathogenesis of PD. Results. 101 putative target genes were identified by the network pharmacology analysis in relation to the treatment of PD with BCT. According to the functional enrichment analysis, the proposed mechanism was primarily related to the transport of neurotransmitters, the metabolism of arachidonic acid, dopamine, and alpha-amino acids, as well as the transport of dopamine and the negative regulation of amino acid transport. 25 distinct endogenous metabolites were shown to be potential biomarkers for the BCT for treating PD based on metabolomics. These metabolites were mostly implicated in the important methionine and cysteine, tyrosine, histidine, and arginine and proline metabolic pathways. These results somewhat agreed with those of the network pharmacology analysis. Conclusions. In conclusion, this study showed that BCT could delay the occurrence and development of PD by improving the brain metabolic disorder of α-Syn mice, which revealed the mechanism of BCT through multitarget and multipathway treatment, and provided a new explanation for the mechanism of anti-PD action. Our research, on the other hand, demonstrated that the network pharmacology-integrated metabolomics approach was a potent tool for discovering the active ingredients and mechanisms underlying the pharmacological effects of traditional Chinese medicine.

Editorial: Experimental and innovative approaches to multi-target treatment of Parkinson's and Alzheimer's diseases - Volume II

“…For example, a method of network pharmacology including a molecular docking technology revealed multi-targets and multichannels of anti-AD activity for two Chinese medicines (Fibraurea recisa Pierre and Curcumin, a major ingredient of traditional Chinese medicine, Curcuma Longa) (Wang et al, 2022;Wu et al, 2022). Bai Chan Ting, a traditional Chinese medicine prescription, consisting of three herbs (Acanthopanax senticosus, Paeonia lactiflora, and Uncaria), was found to produce multi-target and multipathway effects against PD-like pathology in transgenic mice using an integrated strategy of network pharmacology and brain metabolomics (Zhang et al, 2022). In the present article collection, Xu et al clarified the pharmacodynamic mechanisms of Qin-Zhi-Zhu-Dan Formula in treating AD-like pathology and revealed its neuroprotective effects through the regulation of TNFR1-ERK1/2-NF-κBp65 signaling pathway combining animal experiments with network pharmacology analysis [namely, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG)].…”