Scutellarein relieves the death and inflammation of tubular epithelial cells in ischemic kidney injury by degradation of COX-2 protein

Abstract

ObjectivesAcute kidney injury (AKI) is a clinical syndrome that usually caused by ischemia/reperfusion (I/R). Previous studies have revealed the protection of scutellarein against ischemia in nervous system. This study aimed to demonstrate the potential of scutellarein in ischemic AKI. MethodsAnimal model of ischemic AKI was established by clamping bilateral kidney pedicles in Sprague-Dawley rats. HK-2 cells were exposed to oxygen glucose deprivation/reoxygenation (OGD/R) to induce a cell model of AKI. The effects of scutellarein pre-treatment were detected by H&E staining, TUNEL, ELISA, CCK-8, LDH activity assay, ROS generation, flow cytometry, qRT-PCR and western blotting. Bioinformatic analysis was performed to probe the targets of scutellarein. ResultsThe blood urea nitrogen (BUN) and serum creatinine (SCr) levels in rats treated with scutellarein were lower than that in model groups. Scutellarein suppressed the pathological injury of kidney, and dose-dependently inhibited the apoptosis and pro-inflammatory cytokines release (IL-1β, IL-6 and IL-18). Scutellarein prevented OGD/R-induced HK-2 cell loss and cytotoxicity. ROS generation, apoptosis, and inflammation induced by OGD/R were all inhibited by scutellarein. By searching on the TCMSP and Symmap databases, COX-2 was screened out as a target of scutellarein. Scutellarein has no significant impacts on COX-2 mRNA expression, but could inhibit its protein level. Scutellarein promoted COX-2 protein degradation via enhancing autophagy. Furthermore, overexpression of COX-2 partly eliminated the renal protection of scutellarein in HK-2 cells. ConclusionsScutellarein was suggested as a renal protective agent against ischemia-induced damage in AKI. The protective properties of scutellarein may be through inhibition of COX-2.