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

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.