Zhigancao decoction alleviates Parkinson's disease via inhibiting TNF/NF-κB and Ras/ERK-mediated neuroinflammation and apoptosis.

Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons, with neuroinflammation and apoptosis serving as key pathological drivers. In this study, we investigated the traditional herbal formula Zhigancao Decoction (ZGCD) using an integrated strategy that combined network pharmacology prediction, experimental validation in MPTP-induced mouse and MPP+-treated cellular models, and molecular docking simulation. Our results demonstrate that ZGCD alleviates motor deficits and protects dopaminergic neurons by concurrently inhibiting the TNF/NF-κB and Ras/ERK signaling pathways, thereby reducing the release of pro-inflammatory cytokines and markers of apoptosis. In vitro experiments further confirmed that the bioactive components apigenin and bisdemethoxycurcumin contribute to this multi-pathway regulatory effect. This systems pharmacology approach elucidates how ZGCD simultaneously targets interconnected disease-relevant pathways, highlighting its potential as a multi-target therapeutic strategy for neurodegenerative disorders.