In vitro bioaccessibility and alcoholic injury-alleviation effect of Lycium barbarum leaf phenolics

• Lycium barbarum leaf (LBL) phenolics were studied with mimic digestion/transport • 6 of 45 phenolics in LBL showed high bioavailability and cytoprotecting potential • 3,4-Dihydroxymandelic acid (DA) was the most potent agent against alcoholic injury • DA alleviated cellular alcoholic injury by restoring redox balance via YWHAG • LBL is proven to be a potential source of functional foods Lycium barbarum leaf (LBL) is a traditional Chinese vegetable rich in phenolics and with prominent health properties. However, the high bioaccessible LBL phenolics and their activity against alcoholic injury are under study. Herein, in vitro digestion/Caco-2 cell model was used to identify LBL phenolics with high bioaccessibility. In 45 identified LBL phenolics, rutin, sinapic acid, ferulic acid, quercetin, scopoletin, and 3,4-dihydroxymandelic acid (DA) displayed higher content (0.56 ∼ 7.16 μg/mL) and intestinal transport rates (7.34 ∼ 51.28%) after simulated digestion/absorption. Among these phenolics, DA was the most potent agent against alcoholic injury, elevating the viability of alcohol-injured AML-12 cells to 62.57%. By markedly reducing intracellular ROS levels by 28.39 - 45.04%, restoring redox-related indices (decreasing AST/ALT by 56.07%/33.27% and MDA by 27.26%, while enhancing SOD, CAT, and GSH activities), DA significantly alleviated the alcohol-triggered oxidative damage of AML-12 cells. Network pharmacology and molecular docking revealed that DA targeted YWHAG, regulating downstream pathways including PI3K-Akt, Foxo, and MAPK signaling pathway to exert hepatoprotective effects. These findings provide insight into the health properties of LBL and support its further utilization in functional foods.