Qinggan Mingshi Granules Inhibited Ferroptosis to Treat Diabetic Retinopathy in Mice Through NRF2/GPX4 Axis

BACKGROUND: Diabetic retinopathy (DR) is a common microvascular complication of diabetes, which seriously affected the life quality in diabetic patients. Developing novel therapy to improve DR is essential. Qinggan Mingshi granules (QGMS) have been demonstrated with protective effects on DR clinically. However, the mechanisms of QGMS remain unclear. METHOD: In order to more thoroughly investigate the mechanism underlying the positive effects of QGMS on DR, a mouse model of DR was established in this study, and the positive effects of QGMS on the DR mice were observed. Next, the effects of QGMS on ferroptosis and the NRF2/GPX4 axis were investigated. In addition, we used an NRF2 inhibitor to determine whether QGMS inhibits ferroptosis in DR mice via the NRF2/GPX4 axis. RESULT: Our results revealed the therapeutic effects of QGMS on DR including improving the permeability of blood-retina barrier (BRB), reducing the pathological changes and ferroptosis in retina. QGMS also induced the expression of NRF2/GPX4 axis in retina. Furthermore, ML385, an NRF2 inhibitor, abolished the effects of QGMS on DR. CONCLUSION: This study revealed that QGMS can effectively treat DR by alleviating retinal damage through enhancing the expression of NRF2/GPX4 axis-related proteins and thus scavenging of LPOs, ultimately reducing ferroptosis.