Diosmetin exerts anti-oxidative, anti-inflammatory and anti-apoptotic effects to protect against endotoxin-induced acute hepatic failure in mice

Abstract

// You Yang 1 , Xiao-Bao Gong 2 , Li-Gua Huang 2 , Zhen-Xu Wang 3 , Rong-Zhen Wan 4 , Peng Zhang 4 , Qing-Yan Zhang 4 , Zhu Chen 3 and Bao-Shun Zhang 2 1 College of Animal Science and Technology, Southwest University, Chongqing, P. R. China 2 College of Pharmaceutical Sciences, Southwest University, Chongqing, P. R. China 3 Chongqing Institute for Food and Drug Control, Chongqing, P. R. China 4 The Ninth People’s Hospital of Chongqing, Chongqing, P. R. China Correspondence to: Bao-Shun Zhang, email: // Zhu Chen, email: // Keywords : diosmetin, acute hepatic failure, oxidative stress, inflammatory, apoptosis, Pathology Section Received : September 18, 2016 Accepted : February 06, 2017 Published : February 16, 2017 Abstract To investigate the effects and mechanism of diosmetin on acute hepatic failure (AHF), an AHF murine model was established through administration of lipopolysaccharides/D-galactosamine (LPS/D-GalN). In vitro , diosmetin scavenged free radicals. In vivo , diosmetin decreased mortality among mice, blocked the development of histopathological changes and hepatic damage, and suppressed levels of inflammatory mediators and cytokines. In addition, diosmetin prevented the expression of phosphorylated IKK, IκBα, and NF-κB p65 in the NF-κB signaling pathway, and JNK and p38 in the MAPK signaling pathway. Diosmetin also inhibited hepatocyte apoptosis. Thus, diosmetin exerts protective effects against endotoxin-induced acute hepatic failure in mice. The underlying mechanisms are antioxidation, NF-κB signaling inhibition, inflammatory mediator/cytokine attenuation, and hepatocyte apoptosis suppression. Diosmetin is thus a potential drug candidate for use in the treatment of acute hepatic failure.