Parkinson’s disease (PD) is a common neurodegenerative disease characterized by a disorder of the dopaminergic system in the midbrain, causing classical PD motor symptoms. The therapeutic effect of cannabidiol (CBD) on PD has been a research frontier in recent years. However, the pathogenesis of PD and the therapeutic mechanism of cannabinoid remain unclear. To further study the causes of PD and the effect of CBD on PD, we exposed the PD transgenic mouse model to CBD and then estimated the motorial and postural coordination through a modified swim test. Afterwards, the mechanism was investigated via the histopathology of substantia nigra and the gut-brain metabolic analysis in the approach of UHPLC-TOF-MS. The results showed that CBD significantly improved motor deficits of PD model and protected the substantia nigra area. The metabolic function of fatty acid biosynthesis, arginine biosynthesis/metabolism, butanoate (ketone body) metabolism, β-alanine metabolism, and pantothenate/CoA biosynthesis was highlighted in the pathological and therapeutic process along the gut-brain axis. In conclusion, CBD could attenuate PD via the neuroprotective effect on the midbrain. The attenuation of the central nervous system in turn improved motor performance of PD, which might be partially induced by the metabolic interaction between the gut-brain. In view of gut-brain metabolomics, the mechanism of PD pathogenesis and the effect of CBD on PD are highly related to the biosynthesis and metabolism of energy and essential substance.

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.

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