Network pharmacology of cyanidin-3-O-glucoside in oxidative stress-mediated drug-induced liver injury.

Background: Cyanidin-3-O-glucoside (C3G) is a prominent dietary anthocyanin abundant in dark berries, widely recognized for its potent antioxidant and anti-inflammatory properties. Despite its documented hepatoprotective potential, the comprehensive, systems-level molecular mechanisms by which C3G counteracts oxidative stress-mediated drug-induced liver injury (DILI) remain to be fully characterized.

Objective: This study aimed to systematically map the network pharmacology of C3G in the context of oxidative stress-induced inflammatory liver injury, with a specific focus on the Nrf2/HO-1/ROS antioxidant enzyme axis.

Methods: Candidate therapeutic targets of C3G were retrieved from public chemogenomic databases and intersected with disease-associated genes specific to oxidative stress and liver injury. A comprehensive protein–protein interaction (PPI) network was constructed, followed by topological hub gene analysis and GO/KEGG pathway enrichment profiling. To prioritize mechanistically relevant targets, a custom C3G Oxidative Stress Modulation Score was implemented. Structural interactions were further evaluated via molecular docking simulations against the KEAP1 repressor protein.

Results: The integrated network topology successfully identified NFE2L2 (Nrf2), KEAP1, HMOX1 (HO-1), NQO1, SOD2, CAT, GPX1, GCLC, RELA, and mitogen-activated protein kinase (MAPK)-related signaling proteins as central functional nodes. These targets directly link C3G exposure to cellular antioxidant defenses and the modulation of redox-sensitive inflammatory stress pathways.

Conclusion: This study establishes a systems-level pharmacology model demonstrating that cyanidin-3-O-glucoside effectively attenuates oxidative stress-mediated liver injury. This hepatoprotective effect is achieved through the coordinated activation of the Nrf2/HO-1 signaling axis, enhancement of downstream ROS detoxification enzymes, and suppression of inflammatory cascades.