Neuroprotective Effects of Shiliuwei Kangchanzhijing Capsules in Rotenone‐Induced Parkinson's Disease Mouse Model: Involvement of the Parkin/PP2A/α‐Syn Pathway

Parkinson's disease (PD) is a progressive neurodegenerative disorder marked by the loss of dopaminergic neurons in the substantia nigra and the pathological accumulation of α‐synuclein (α‐Syn). Rotenone, a mitochondrial complex I inhibitor, reliably reproduces these hallmark features and is therefore widely used to establish experimental PD models. Shiliuwei Kangchanzhijing capsules (SLW‐KCZJ capsules), a traditional Chinese medicine (TCM) formulation comprising 16 herbal components, were specifically developed for PD management. This study systematically evaluated the neuroprotective effects and underlying mechanisms of SLW‐KCZJ in a rotenone‐induced PD mouse model. SLW‐KCZJ treatment significantly improved movement distance and balance–coordination, attenuated neuronal loss in the substantia nigra, and markedly suppressed neuroinflammatory responses. At the molecular level, the capsules increased tyrosine hydroxylase expression by approximately 200% and elevated Parkin and protein phosphatase 2A levels by approximately 60% and 80%, respectively. In contrast, they robustly inhibited polo‐like kinase 2 expression and reduced α‐Syn levels by approximately 60% and 40%. The intervention also increased striatal dopamine (DA) and homovanillic acid levels while lowering neurofilament light chain and oligomeric α‐Syn. In summary, this study provides the first evidence that SLW‐KCZJ capsules exert neuroprotective effects by modulating the Parkin/PP2A/α‐Syn signaling pathway, offering a promising TCM‐based therapeutic strategy for PD.