Widely targeted metabolomics, network pharmacology and molecular docking analyses exploring the mechanistic basis for the antioxidant activity of three golden camellia species

This study employed antioxidant assays, metabolomics (UPLC-MS/MS), network pharmacology, and molecular docking approaches to explore the antioxidant characteristics, underlying molecular mechanisms, and potential applications of the leaves of Camellia debaoensis , Camellia mingii , and Camellia rostrata . All three of these species exhibited robust antioxidant activity, with C. rostrata slightly outperforming the others. The most differentially abundant metabolites among these three species were flavonoids and phenolic acids, with C. debaoensis and C. mingii exhibiting more similar metabolite profiles as compared to the more varied profile of C. rostrata . In network pharmacology analyses, 91 and 83 antioxidant targets for C. debaoensis and C. mingii were identified that were primarily associated with flavonoids, whereas 56 targets for C. rostrata -associated phenolic acids were identified. The most enriched pathway for antioxidants across all three species was the “pathways in cancer” pathway. Additionally, 12 antioxidant targets in C. rostrata were enriched in the “coronavirus disease - COVID-19” pathway. The core metabolites in C. debaoensis and C. mingii were naringenin, tangeretin, kaempferitrin, and phloretin, whereas those in C. rostrata included ferulic acid, isoferulic acid, and caffeic acid. Molecular docking showed analyses revealed the binding affinity of naringenin for TNF and CASP8 in C. debaoensis , supporting its anti-inflammatory potential, while its affinity for SRC in C. mingii was indicative of potential cardiovascular benefits. Caffeic acid from C. rostrata also exhibited a high degree of affinity for EGFR, indicating that it may offer value for the prevention and treatment of cancer. • The three golden camellia species exhibit strong antioxidant activity, mainly attributed to flavonoids and phenolic acids, with C. rostrata being the most potent. • Comparative metabolomics and network pharmacology reveal that phylogenetic proximity shapes antioxidant strategies in golden camellias. • Each species displays a unique pharmacological profile: C. debaoensis targets inflammation, C. mingii supports cardiovascular health, and C. rostrata holds anticancer potential.