A combined strategy based on network pharmacology, molecular docking, and experimental validation to explore the potential mechanism of action of Peitushugan decoction for Parkinson's disease

Context: Parkinson’s disease (PD) stands as the second most prevalent neurodegenerative condition worldwide, with oxidative stress and neuroinflammation are the main pathogenic mechanisms. The Peitushugan decoction (PTSGD), a classical formula used in Traditional Chinese Medicine, is commonly used clinically for treating PD with satisfactory efficacy. However, the precise mode of operation for PTSGD in addressing PD is not yet fully elucidated. Objective: This investigation sought to elucidate the possible functional mechanism of PTSGD in PD management through the application of network pharmacology (NP) approaches, molecular docking simulations, and empirical verification. Materials & methods: Utilizing NP to screen for the main active ingredients and key targets of PTSGD in treating PD. The results of NP were validated using two methods: molecular docking and animal experiments with rotenone-treated mice.Results: NP depicted that quercetin, kaempferol, luteolin, and isorhamnetin in PTSGD might treat PD by modulating the p38MAPK/NFκB signaling pathway. Behavioral experiments illustrated that the mice in the PTSGD cohort depicted improvements than the model cohort. Molecular biology experiments exhibited that in contrast to the model cohort, the level of central and peripheral inflammatory factors was diminished, α-synuclein (α-Syn) and Iba-1 expression was reduced, and TH-positive cell expression was increased in the PTSGD cohort. Discussion and Conclusion: The active ingredients of PTSGD may mediate the immune-inflammatory response by targeting the p38MAPK/NFκB signaling pathway, thus inhibiting microglial activation, reducing the abnormal aggregation of α-Syn, and protecting dopaminergic neurons from having a therapeutic effect on PD.