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Effects of Armepavine Against Hepatic Fibrosis Induced by Thioacetamide in Rats
Author(s) -
Weng TingChun,
Shen ChienChang,
Chiu YungTsung,
Lin YunLian,
Huang YiTsau
Publication year - 2012
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.3539
Subject(s) - thioacetamide , hepatic stellate cell , in vivo , hepatic fibrosis , endocrinology , aspartate transaminase , medicine , fibrosis , hepatocyte , chemistry , alanine transaminase , kupffer cell , microbiology and biotechnology , biology , in vitro , biochemistry , alkaline phosphatase , enzyme
The aim of this study was to investigate if armepavine (Arm, C 19 H 23 O 3 N) could exert inhibitory effects against hepatic fibrosis in rats. A cell line of rat hepatic stellate cells (HSC‐T6) was stimulated with tumour necrosis factor‐α (TNF‐α) to evaluate the inhibitory effects of Arm. Rats were injected with thioacetamide (TAA; 300 mg/kg, intraperitoneally) thrice a week for 4 weeks to induce hepatic fibrosis, with Arm (3 or 10 mg/kg) given by gavage twice a day. Liver sections were taken for western blotting, fibrosis scoring and immunofluorescence staining. Arm (1–10 µ m ) concentration‐dependently attenuated TNF‐α‐stimulated: (i) protein expressions of α‐smooth muscle actin (α‐SMA), collagen type I and angiopoietin‐1; (ii) H 2 O 2 production; and (iii) NF‐κB, JunD and C/EBPß (cytidine‐cytidine‐adenosine‐adenosine‐thymidine (CCAAT)/enhancer binding protein‐ß (EBPß)) nuclear translocations in HSC‐T6 cells. In vivo Arm treatment significantly reduced plasma aspartate transaminase and alanine transaminase levels, hepatic α‐SMA expression and collagen contents, and fibrosis scores of TAA‐injected rats. Moreover, Arm treatment decreased α‐SMA‐ and NF‐κB‐positive cells in immunohistochemical staining, and mRNA expression levels of IL‐6, TGF‐ß1, TIMP‐1, col1α2, iNOS and ICAM‐1 genes, but up‐regulated the metallothionein gene in the livers of TAA‐injected rats. Our results indicated that Arm exerted both in vitro and in vivo antifibrotic effects in rats, with inhibition of NF‐κB, JunD and C/EBPß pathways. Copyright © 2011 John Wiley & Sons, Ltd.