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: Ting-Chun Weng, Chien-Chang Shen, Yung-Tsung Chiu, Yun-Lian Lin, Yi-Tsau Huang
• Journal: Phytotherapy research : PTR (Phytother Res) Vol. 26 Issue 3 Pg. 344-53 (Mar 2012) ISSN: 1099-1573 [Electronic] England
• PMID: 21717514 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 John Wiley & Sons, Ltd.

Chemical References

• Actins
• Angiopoietin-1
• Angpt1 protein, rat
• Benzylisoquinolines
• CCAAT-Enhancer-Binding Protein-beta
• Collagen Type I
• Cytokines
• NF-kappa B
• Transcription Factors
• smooth muscle actin, rat
• Thioacetamide
• Metallothionein
• Hydrogen Peroxide
• Aspartate Aminotransferases
• Alanine Transaminase
• armepavine

Topics

• Actins (genetics, metabolism)
• Active Transport, Cell Nucleus
• Alanine Transaminase (blood)
• Angiopoietin-1 (genetics, metabolism)
• Animals
• Aspartate Aminotransferases (blood)
• Benzylisoquinolines (administration & dosage, therapeutic use)
• Blotting, Western
• CCAAT-Enhancer-Binding Protein-beta (genetics, metabolism)
• Collagen Type I (metabolism)
• Cytokines (genetics, metabolism)
• Dose-Response Relationship, Drug
• Fluorescent Antibody Technique
• Hepatic Stellate Cells (cytology, drug effects, metabolism)
• Hydrogen Peroxide (metabolism)
• Liver Cirrhosis (chemically induced, drug therapy, pathology)
• Male
• Metallothionein (genetics, metabolism)
• NF-kappa B (metabolism)
• Phytotherapy
• Rats
• Rats, Sprague-Dawley
• Thioacetamide (administration & dosage, adverse effects)
• Transcription Factors (genetics, metabolism)
• Transcription, Genetic