Coixol Protects Against Acute Kidney Injury by Reducing Cell Senescence.

Acute kidney injury (AKI) is associated with increased in-hospital mortality, yet effective therapeutic agents remain limited. Coixol, a polyphenolic compound derived from Coix, possesses anti-inflammatory properties, but its role in AKI remains unclear. In this study, we demonstrate that Coixol exerts protective effects against ischemia/reperfusion (I/R)-induced AKI by alleviating cellular senescence. Coixol treatment significantly reduced serum creatinine (SCr) and blood urea nitrogen (BUN) levels and decreased the expression of KIM1 and NGAL. RNA sequencing and validation experiments revealed that Coixol suppressed cellular senescence in AKI. Through a weighted gene co-expression network analysis and machine learning, we identified Plaur as a key target of Coixol, which was further validated using RNA-seq data. Notably, Plaur overexpression in AKI mice diminished the protective effects of Coixol, confirming its crucial role. Additionally, molecular docking and molecular dynamics simulations demonstrated strong binding affinity between Coixol and Plaur. These findings highlight Coixol as a promising renal protective agent targeting Plaur and cellular senescence in AKI.