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.