title: Paeoniflorin protects against ANIT-induced cholestasis by ameliorating oxidative stress in rats.
abstract: Paeoniflorin, one of the primary bioactive components in Chi shao, are widely used in traditional Chinese medicine. A lot of evidences suggest that Paeoniflorin has potential anti-oxidant effects. However, whether Paeoniflorin plays roles in cholestasis is unclear. In this study, we examined the protective effect of Paeoniforin against alpha-naphthylisothicaynate (ANIT)-induced cholestasis in rats. Our data demonstrated that the high (0.2 g/kg body weight) and medium (0.1 g/kg body weight) doses of Paeoniflorin significantly prevented ANIT-induced changes in bile flow and the serum levels of total bilirubin, direct bilirubin, total bile acid, γ-glutamyltranspeptidase, glutamate-pyruvate transaminase, glutamate-oxaloacetic transaminase and alkaline phosphatase. Moreover, we also found that Paeoniflorin significantly inhibited nitric oxide and malondialdehyde production, and restored glutathione decrease induced by ANIT. EPR data further indicated that Paeoniflorin inhibited ANIT-mediated reactive oxygen species (ROS) production. The overexpression of NADPH oxidase 4 induced by ANIT were significantly reversed when treated with Paeoniflorin, suggesting that Paeoniflorin could scavenge ROS via inhibiting NADPH oxidase 4 expression. Paeoniflorin treatment could also relieve ANIT-induced liver pathological injuries as indicated by histological assay. These findings indicate that Paeoniflorin exerts a dose-dependent protective effect on ANIT-induced cholestatic liver injury in rats, and the mechanism of this activity is related to its attenuation of oxidative stress in liver tissue.
authors.affiliation: China Military Institute of Chinese Medicine, 100#, the 4th Ring Road, Beijing 100039, PR China. zhaoyl2855@126.com
authors.forename: Yanling
authors.initials: Y
authors.lastname: Zhao
authors.forename: Guangde
authors.initials: G
authors.lastname: Zhou
authors.forename: Jiabo
authors.initials: J
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Jia
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Ruisheng
authors.initials: R
authors.lastname: Li
authors.forename: Limei
authors.initials: L
authors.lastname: Shan
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.forename: Xueai
authors.initials: X
authors.lastname: Song
authors.forename: Shijing
authors.initials: S
authors.lastname: Liu
authors.forename: Xiaohe
authors.initials: X
authors.lastname: Xiao
mesh_terms: D015058:1-Naphthylisothiocyanate / Q000633:toxicity*; D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002779:Cholestasis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D005960:Glucosides / Q000494:pharmacology*; D039821:Monoterpenes; D018384:Oxidative Stress; D051381:Rats; D006027:Glycosides
chemical_list: D015058:1-Naphthylisothiocyanate; D001565:Benzoates; D001952:Bridged-Ring Compounds; D005960:Glucosides; D039821:Monoterpenes; C015423:peoniflorin; D006027:Glycosides
keywords: Paeoniflorin; Rats; Reactive oxygen species (ROS); α-Naphthylisothiocyanate (ANIT)