UPLC-QTOF-MS/MS-Guided phytochemical characterization and molecular docking of Rosa rusoga extract for Keap1–Nrf2 modulation

Rosa rugosa extract (RRE) is traditionally used for its antioxidant properties, but its molecular mechanisms remain unclear. This study investigated the ability of RRE to activate the Keap1-Nrf2 pathway, a key regulator of oxidative stress defense. UPLC-QTOF-MS/MS identified 91 phytochemicals, with 10 major compounds, including flavonoids, triterpenoids, and alkaloids. Molecular docking revealed that 3-trans-p-coumaroylrotundic acid, gallocatechin-(4→8)-epicatechin, and ginsenoside Rf interact with the Kelch domain of Keap1, potentially preventing Nrf2 degradation. Functional validation via Nrf2-knockout zebrafish (nfe2l2a^dl703/dl703) confirmed that RRE enhances oxidative stress resistance and upregulates the expression of antioxidant genes (gstp1 and prdx1) in an Nrf2-dependent manner. These findings suggest that RRE acts as a natural Keap1 inhibitor, supporting Nrf2-driven cytoprotection. This study provides a mechanistic basis for the traditional use of RRE in oxidative stress management, highlighting its potential for nutraceutical and therapeutic applications.