In-depth profiling of Phenolics in strawberries and their potential modulatory effects on the oxidative stress-disease Axis: Insights from UHPLC-QTOF-MS-based untargeted metabolomics, network pharmacology, and molecular docking

Strawberry phenolics, contributing to its potent antioxidant properties, yet due to limitations in detection and analysis techniques, the phenolic profiling of strawberries remains incomplete, hindering a deeper understanding of their mechanisms. In this study, a dual-phase extraction method was applied to extract both free and bound phenolics, followed by UHPLC-QTOF-MS-based untargeted metabolomics. A total of 57 phenolics were annotated, with 12 further identified using standards. Notably, twenty-six phenolics were first reported in strawberries. Network pharmacology analysis revealed that phenolic targets associated with oxidative stress-driven disease are primarily enriched in SRC, PIK3CA, PIK3R1, HSP90AA1, and TP53, which exert their effects through the PI3K-AKT signaling pathway. Molecular docking simulations further elucidated the interaction mechanisms, suggesting that strawberry phenolics modulate the oxidative stress-disease axis. These findings have enhanced our understanding of the phenolic profile of strawberries and lay the groundwork for further research into the physiological roles of strawberry phenolics.