title: Effects of armepavine against hepatic fibrosis induced by thioacetamide in rats.
abstract: The aim of this study was to investigate if armepavine (Arm, C₁₉H₂₃O₃N) 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 µm) concentration-dependently attenuated TNF-α-stimulated: (i) protein expressions of α-smooth muscle actin (α-SMA), collagen type I and angiopoietin-1; (ii) H₂O₂ 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.
authors: Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Ting-Chun
authors: TC
authors: Weng
authors: Chien-Chang
authors: CC
authors: Shen
authors: Yung-Tsung
authors: YT
authors: Chiu
authors: Yun-Lian
authors: YL
authors: Lin
authors: Yi-Tsau
authors: YT
authors: Huang
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D021581:Active Transport, Cell Nucleus; D000410:Alanine Transaminase / Q000097:blood; D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D044182:Benzylisoquinolines / Q000008:administration & dosage / Q000627:therapeutic use*; D015153:Blotting, Western; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008103:Liver Cirrhosis / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D008517:Phytotherapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013853:Thioacetamide / Q000008:administration & dosage / Q000009:adverse effects*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D000199:Actins; D000410:Alanine Transaminase; D042683:Angiopoietin-1; D001219:Aspartate Aminotransferases; D044182:Benzylisoquinolines; D022782:CCAAT-Enhancer-Binding Protein-beta; D024042:Collagen Type I; D016207:Cytokines; D006861:Hydrogen Peroxide; D008668:Metallothionein; D016328:NF-kappa B; D013853:Thioacetamide; D014157:Transcription Factors; C467629:Angpt1 protein, rat; C498862:Acta2 protein, rat; C064689:armepavine