title: Paeoniflorin ameliorates cholestasis via regulating hepatic transporters and suppressing inflammation in ANIT-fed rats.
abstract: Paeoniflorin has shown the obvious effect on cholestasis according to our previous research. However, its mechanism has not been absolutely explored yet. This study aims at evaluating the potential effect of paeoniflorin on alpha-naphthylisothiocyanate (ANIT) -induced cholestasis by inhibiting nuclear factor kappa-B (NF-κB) and simultaneously regulating hepatocyte transporters. Cholestasis was induced by administration of ANIT. The effect of paeoniflorin on serum indices such as total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyltranspeptidase (γ-GT), total bile acid (TBA) and histopathology of liver were determined. Liver protein levels of NF-κB, interleukin 1β (IL-1β) and the hepatocyte transporters such as Na+/taurocholate cotransporting polypeptide (NTCP), bile salt export pump (BSEP), multidrug resistance-associated protein 2 (MRP2) and cholesterol 7α-hydroxylase (Cyp7a1) were investigated by western blotting. The results demonstrated that paeoniflorin could decrease serum ALT, AST, ALP, γ-GT, TBIL, DBIL and TBA in ANIT-treated rats. Histological examination revealed that rats treated with paeoniflorin represented fewer neutrophils infiltration, edema and necrosis in liver tissue compared with ANIT rats. Moreover, paeoniflorin significantly reduced the over expressions of NF-κB and IL-1β induced by ANIT in liver tissue. In addition, the relative protein expressions of NTCP, BSEP, MRP2 but not Cyp7a1 were also restored by paeoniflorin. The potential mechanism of paeoniflorin in alleviating ANIT-induced cholestasis seems to be related to reduce the over expressions of NF-κB and hepatocyte transporters such as NTCP, BSEP as well as MRP2.
authors.affiliation: Department of Pharmacy, 302 Hospital of People's Liberation Army, Beijing, People's Republic of China. Electronic address: zhaoyl2855@126.com.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pharmacy, Xindu District Shibantan Public Hospital, Chengdu, People's Republic of China.
authors.forename: Xuan
authors.initials: X
authors.lastname: He
authors.affiliation: Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu,People's Republic of China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Pharmacy, 302 Hospital of People's Liberation Army, Beijing, People's Republic of China; Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu,People's Republic of China.
authors.forename: Jianxia
authors.initials: J
authors.lastname: Wen
authors.affiliation: Department of Pharmacy, 302 Hospital of People's Liberation Army, Beijing, People's Republic of China.
authors.forename: Pengyan
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Pharmacy, 302 Hospital of People's Liberation Army, Beijing, People's Republic of China.
authors.forename: Jiabo
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, 302 Hospital of People's Liberation Army, Beijing, People's Republic of China.
authors.forename: Ruisheng
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Pharmacy, 302 Hospital of People's Liberation Army, Beijing, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Pharmacy, 302 Hospital of People's Liberation Army, Beijing, People's Republic of China.
authors.forename: Shizhang
authors.initials: S
authors.lastname: Wei
authors.affiliation: Department of Pharmacy, 302 Hospital of People's Liberation Army, Beijing, People's Republic of China.
authors.forename: Haotian
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pharmacy, 302 Hospital of People's Liberation Army, Beijing, People's Republic of China.
authors.forename: Xuelin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Pharmacy, 302 Hospital of People's Liberation Army, Beijing, People's Republic of China.
authors.forename: Kun
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Pharmacy, 302 Hospital of People's Liberation Army, Beijing, People's Republic of China.
authors.forename: Honghong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, 302 Hospital of People's Liberation Army, Beijing, People's Republic of China. Electronic address: xiaoxiaohe@126.com.
authors.forename: Xiaohe
authors.initials: X
authors.lastname: Xiao
mesh_terms: D015058:1-Naphthylisothiocyanate; D000818:Animals; D001646:Bile / Q000737:chemistry / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D002352:Carrier Proteins / Q000378:metabolism*; D002779:Cholestasis / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005960:Glucosides / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced* / Q000517:prevention & control*; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D039821:Monoterpenes / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D009336:Necrosis; D020556:Neutrophil Infiltration / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D006027:Glycosides
chemical_list: D015058:1-Naphthylisothiocyanate; D015415:Biomarkers; D002352:Carrier Proteins; D005960:Glucosides; D039821:Monoterpenes; D016328:NF-kappa B; C015423:peoniflorin; D006027:Glycosides
keywords: BSEP; Cholestasis; MRP2; NF-κB; NTCP; Paeoniflorin