Network Pharmacology Analysis Reveals Multi-Target Hepatoprotective Mechanisms of a Multi-Component Pharmacopuncture Against Ephedra-Associated Liver Injury with Implications for Mitochondrial Quality Control.

Background and Objectives: Drug-induced liver injury (DILI) is increasingly associated with the use of herbal medicines. Ephedra sinica (ES) occasionally induces hepatocellular injury, yet therapeutic strategies for herb-induced liver injury are limited. This study investigated the potential mechanisms of a multicomponent pharmacopuncture formulation (VP) in ES-associated hepatotoxicity. Materials and Methods: Bioactive constituents of VP were collected from pharmacological databases and literature. The physicochemical properties were evaluated using SwissADME. Compound-target interactions were identified using the STITCH database and integrated with DILI-related genes retrieved from GeneCards (relevance score ≥ 5.0). Protein-protein interaction network analysis, Gene Ontology enrichment, and KEGG pathway analyses were performed. Results: A total of 22 overlapping targets were identified. A nine-gene module-comprising TNF, IL6, STAT3, CASP3, PINK1, PRKN, NFE2L2, HMOX1, and ABCB11-was associated with key biological processes, including inflammatory signaling, mitochondrial quality control, oxidative stress regulation, and hepatobiliary transport. Conclusions: These findings suggest that VP may modulate multiple biological processes relevant to hepatotoxic stress, including inflammatory signaling, mitochondrial quality control, and bile acid transport. These results provide a plausible mechanistic framework for further investigation, pending experimental validation.