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.