Zingerone ameliorates lipopolysaccharide-induced acute kidney injury by inhibiting Toll-like receptor 4 signaling pathway

Abstract

Acute kidney injury (AKI) is a serious complication of sepsis. Zingerone, a phenolic alkanone isolated from ginger, has been reported to have anti-inflammatory effect. The aim of this study was to investigate the therapeutic effects of zingerone on lipopolysaccharide (LPS)-induced AKI in mice. Zingerone was administrated 1h after LPS challenge. The production of blood urea nitrogen (BUN) and creatinine were measured in this study. The expressions of inflammatory cytokines in serum and kidney tissues were detected by ELISA. The expressions of Toll-like receptor 4 (TLR4), MyD88, TRIF, Nuclear factor Kappa B (NF-κB) and IκB were measured by Western blotting. The results showed that zingerone suppressed LPS-induced BUN, creatinine, and inflammatory cytokines TNF-α, IL-6 and IL-1β levels in a dose-dependent manner. Zingerone also attenuated LPS-induced kidney histopathologic changes. Furthermore, zingerone was found to inhibit LPS-induced TLR4, MyD88, TRIF expression and NF-κB activation. In conclusion, the current study demonstrated that zingerone inhibited LPS-induced AKI by suppressing TLR4/NF-κB signaling pathway.

Keywords: Acute kidney injury; LPS; NF-κB; TLR4; Zingerone.