P-coumaric-acid ameliorates acute kidney injury induced by ischemia-reperfusion injury via suppressing ferroptosis

AKI resulting from IRI has hindered the development of therapeutic drugs due to unclear pathogenesis. Natural herbal monomers, grounded in the concept of food and medicine sharing the same origin, may provide a novel direction for the development of AKI treatments. p-CA, which is abundantly found in vegetables, fruits, and grains, exhibits anti-apoptotic and antioxidant properties, mechanisms that are closely associated with the pathological processes of AKI. Therefore, p-CA could be developed as an effective therapeutic agent for the treatment of AKI. This study aims to elucidate the molecular mechanisms through which p-CA mitigates renal injury in AKI. Kidney injury was evaluated using HE and Masson staining. The expression of iron death-related proteins was assessed using ELISA, qPCR, iron assay, IF, and WB. p-CA inhibits renal damage induced by ischemia-reperfusion injury, regulates iron ion homeostasis in the kidneys, and concurrently suppresses the pathological process of Ferroptosis. Additionally, p-CA improves renal injury induced by IRI in vivo and significantly inhibits Ferroptosis. Furthermore, p-CA demonstrates notable protective effects against cell damage induced by H/R and Erastin in vitro. Mechanistically, this study reveals that p-CA significantly upregulates the expression of ferroptosis-related proteins, including SLC7A11 and GPX4, ultimately leading to effective alleviation of AKI. p-CA demonstrates significant efficacy in ameliorating kidney injury and inhibiting Ferroptosis. The findings from this study are expected to provide experimental evidence for the development of novel therapeutics for AKI.

Acute kidney injury; Ferroptosis; Glutathione; Ischemia-reperfusion injury; P-coumaric-acid.