Metabolomics, network pharmacology, and molecular docking reveal the anti-melanogenic efficacy and mechanism of gallocatechin in Rosa rugosa ‘Dian hong’ ethanol-water extracts

First integrated network pharmacology and metabolomics study to elucidate the skin-whitening mechanism of Rosa rugosa ‘Dianhong’ (DH rose), a variety whose bioactive constituents and anti-melanogenic effects have not been previously characterized. • DH rose extracts demonstrated significant inhibition of tyrosinase activity and melanin production in both cellular and zebrafish models. • Gallocatechin was identified as a novel anti-melanogenic compound, expanding the current repertoire of natural tyrosinase inhibitors, with strong binding affinities to core targets (AKT1, TP53) confirmed by molecular docking. • Multi-target mechanism involving regulation of Rap1, PI3K-Akt, and MAPK signaling pathways, with core targets including EGFR, AKT1, SRC, and PTGS2. This study employed an integrated approach combining network pharmacology and metabolomics to systematically evaluate the anti-melanogenic potential of Rosa rugosa ‘Dianhong’ (DH rose) extracts, while also utilizing correlation analysis and molecular docking to predict novel anti-melanogenic compounds. The chemical constituents of DH rose extracts were identified using UPLC-MS/MS, followed by network pharmacology screening of active component targets, which were mapped against known anti-melanogenic targets to construct a compound-target-pathway network for identifying core targets and key signaling pathways. The inhibitory effects of the extracts on melanogenesis were subsequently validated in both cellular and zebrafish models, demonstrating that DH rose extracts significantly inhibited tyrosinase activity and melanin production. Integrated metabolomics and network pharmacology analyses suggested that the anti-melanogenic effect is mediated through the regulation of core targets such as EGFR, AKT1, SRC, and PTGS2, and pathways including Rap1, PI3K-Akt, and MAPK. Correlation analysis identified gallocatechin as a key bioactive compound, which significantly suppressed tyrosinase activity and reduced melanin levels in an α-MSH-induced zebrafish model, while molecular docking further confirmed strong binding affinities between gallocatechin and core targets. In conclusion, to our knowledge, this study applies an integrated network pharmacology and metabolomics strategy to elucidate the multi-target anti-melanogenic mechanism of DH rose, a specific variety whose bioactive constituents and anti-melanogenic effects have not been previously characterized. Notably, gallocatechin was identified as a rarely reported, candidate new anti-melanogenic compound, provide new insights into the current repertoire of natural tyrosinase inhibitors. These findings position DH rose as a promising candidate for cosmetic anti-melanogenic applications and highlight gallocatechin as a valuable lead compound for further development.