Daphne jejudoenosis and its bioactive compounds protect kidney proximal tubular cells against hydrogen peroxide-induced oxidative stress

Abstract Reactive oxygen species (ROS), particularly hydrogen peroxide (H 2 O 2 ), are implicated in oxidative stress and kidney tubular injury. Daphne jejudoensis (DJ), a plant native to Jeju Island, has demonstrated anti-inflammatory properties, but its effects on kidney diseases remain unexplored. This study investigated the impact of DJ extract and its compounds, daphnin and daphnetin, on H 2 O 2 -induced cell death and ROS production in kidney proximal tubular HK-2 cells. Extracts from the DJ plant parts significantly enhanced cell viability in H 2 O 2 -exposed cells. The DJ leaf extract significantly reduced levels of superoxide anion and hydroxyl radical and prevented the decrease in superoxide dismutase (SOD) activity. Fractions from 70% ethanol DJ leaf extract exhibited protective effects against H 2 O 2 -induced injury, with the ethyl acetate fraction standing out for its ability to enhance antioxidant enzyme activities. Daphnin and daphnetin, major bioactive compounds of DJ extract, significantly increased cell viability and reduced ROS production in H 2 O 2 -exposed cells, restoring SOD and catalase activities. Conclusively, DJ extract and the main compounds, daphnin and daphnetin, protect kidney proximal tubular cells against H 2 O 2 -induced oxidative stress by reducing ROS production and enhancing antioxidant defenses. These findings suggest the potential therapeutic use of DJ in kidney diseases associated with oxidative stress.