Didymin ameliorates hepatic injury through inhibition of MAPK and NF-κB pathways by up-regulating RKIP expression

Abstract

A flavone was isolated from Origanum vulgare and identified as didymin (O. vulgare didymin, OVD). The protective effect and mechanism of OVD on acute liver injury was then assessed in vivo and in vitro. Our results showed that OVD significantly alleviated CCl4-induced liver injury in mice and markedly decreased serum ALT and AST activities. OVD treatment significantly reduced CYP2E1 activity, lipid peroxidation level, ROS generation, NO production and pro-inflammatory cytokines (such as TNF-α, IL-6 and IL-1β) in liver tissues and RAW 264.7 cells, but enhanced the hepatic antioxidative enzymes activities. Further study showed that OVD significantly inhibited the NF-κB and MAPK pathways. Interestingly, OVD notably enhanced Raf kinase inhibitor protein (RKIP) expression, and the effects of OVD on histological changes, oxidative stress and inflammation was largely abolished by the RKIP specific inhibitor locostatin. Our findings indicate that OVD can ameliorate CCl4-induced liver injury, which may be ascribed to its radical scavenging action, antioxidant activity, and modulation of MAPK and NF-κB signaling pathways.