Wogonin improves high glucose-induced ARPE-19 cell damage by inhibiting ferroptosis via suppressing the cGAS-STING pathway.

To investigate the protective effect of wogonin against high glucose (HG)-induced ARPE-19 cell injury and to elucidate its mechanism of action. The effects of Wogonin on cell proliferation and apoptosis were systematically evaluated by a high glucose-induced ARPE-19 cell injury model using different doses of Wogonin for intervention. Meanwhile, intracellular reactive oxygen species (ROS) levels, iron ion accumulation and glutathione (GSH) depletion were detected, and the expression changes of apoptosis-related proteins, ferroptosis -related proteins, and cGAS-STING pathway proteins were analyzed. In addition, the cGAS agonist SR-717 was co-administered on the basis of Wogonin intervention to further investigate whether SR-717 could reverse the effects of Wogonin on cells. Wogonin significantly increased cell viability and reduced apoptosis in response to HG. Wogonin also alleviated oxidative stress by decreasing intracellular ROS and iron accumulation while inhibiting glutathione depletion. In addition, wogonin inhibited HG-induced ARPE-19 cell injury by inhibiting the cGAS‒STING signaling pathway and promoting the expression of the cellular GPX4 and SLC7A11 proteins. Wogonin inhibits ferroptosis by suppressing the cGAS-STING signaling pathway and has a protective effect against HG-induced ARPE-19 cell injury, suggesting that it may be used as a therapeutic agent to alleviate DR.