Coptisine improves sepsis-induced acute kidney injury by inhibiting ferroptosis

Sepsis-associated acute kidney injury (SA-AKI) is a life-threatening complication characterized by high morbidity and mortality. However, effective pharmacological therapies are currently unavailable. Ferroptosis, an iron-dependent form of regulated cell death, plays a pivotal role in the pathogenesis of SA-AKI. Coptisine, a natural isoquinoline alkaloid derived from Coptis chinensis, has demonstrated anti-inflammatory and antioxidant effects, but its specific role in SA-AKI remains to be elucidated. In this study, we investigated the protective effects of Coptisine against SA-AKI and the underlying mechanisms involved. Using a cecal ligation and puncture (CLP) mouse model, our study revealed that administering Coptisine significantly alleviated renal injury and inflammation, decreased oxidative stress, and inhibited ferroptosis in kidney tissues. In vitro studies showed that Coptisine suppressed LPS-induced ferroptotic injury in HK2 cells. Nevertheless, this protective effect was reversed by Nrf2 knockdown or iron supplementation. Mechanistically, Coptisine upregulated the levels of Nrf2 and GPX4, resulting in reduced ROS, MDA, and Fe²⁺ levels, while enhancing GSH content. Collectively, our findings indicate that Coptisine alleviates sepsis-induced AKI by inhibiting ferroptosis through the activation of the Nrf2 signaling pathway, highlighting its potential as a therapeutic agent for SA-AKI.