Eucommia ulmoides leaf extract attenuates cisplatin-induced kidney injury in mice through endoplasmic reticulum stress and biometabolic mechanism

Abstract

Abstract Cisplatin (CP) is a widely utilized anticancer drug but is associated with significant side effects, notably acute kidney injury (AKI). Eucommia ulmoides leaf (EUL), a valuable Chinese herbal remedy, is known for its renoprotective properties. However, the function and underlying pathways of EUL in AKI therapy have remained largely unexplored. This research aimed to elucidate the protective roles of EUL in an AKI mouse model through biochemical assays, and histopathological andexaminations while also investigating the underlying mechanisms via endoplasmic reticulum (ER) stress-related protein expression analysis and metabolomics. The findings demonstrated that pretreatment with orally administered EUL significantly reduced blood urea nitrogen (BUN) and serum creatinine (SCr) levels, ameliorated CP-induced kidney histopathological injuries, and attenuated CP-induced ER stress by reducing the protein expressions of PERK, IRE 1α, GRP78, ATF6, ATF4, and CHOP. Additionally, metabolomics analysis identified 31 significant differential metabolites affected by EUL treatment in AKI mice, impacting pathways related to taurine and hypotaurine metabolism, lysine degradation, and steroid hormone biosynthesis. These findings suggested that EUL could offer valuable insights for potential CP-induced AKI treatment strategies.