A pilot study on the mechanism of Guasha in treating Parkinson's disease based on molecular level and ultra-trace proteomics analysis

Guasha is a widely applied non-pharmacological therapy of traditional Chinese medicine (TCM), which has been proved to be effective in the treatment of Parkinson's disease (PD). The objective of this study was to explore the mechanisms of Guasha therapy in the pathological processes including neuroinflammation in PD. After 3 Guasha courses, a reduction in α-synuclein aggregation and alleviation of microglia activation were observed in the substantia nigra pars compacta (SNpc). Furthermore, levels of TNF-α, IL-1β and IFN-γ in the SNpc decreased, while plasma TGF-β, IL-4 and IL-10 increased. Moreover, both TH protein and mRNA levels in the SNpc, as well as dopamine levels in the striatum, exhibited an increase. The proteomics analysis results based on plasma-derived exosomes revealed a total of 943 differentially expressed proteins identified. Compared to the model group, the Guasha group screened for 82 differential proteins, with 30 upregulated and 52 downregulated. The improvement of pathological changes in the PD model mice treated with Guasha primarily involves biological processes such as oxidative stress, immune response and inflammation, and cellular structure regulation. It involves signaling pathways related to aldosterone synthesis and secretion, adrenergic signaling in myocardial cells, COVID-19-related inflammatory signaling, and neurotrophic signaling. Collectively, the mechanisms of Guasha for treating PD might be closely related to inhibiting microglial cell activation-mediated neuroinflammation, regulating oxidative stress, cellular structure, aldosterone synthesis and secretion-mediated electrolyte balance, as well as noradrenergic signaling-mediated neuroprotection. These findings provided new insight for Guasha in treating PD and would potentially enhance therapeutic interventions.