Abstract
Cholestatic liver fibrosis, characterized by excessive accumulation of extracellular matrix (ECM) proteins, is associated with bile acid-induced oxidative stress and lipid peroxidation. We evaluated the therapeutic or protective effect of an aqueous extract of Artemisia iwayomogi Kitamura (WAI) in a rat bile duct ligation (BDL)-induced hepatic fibrogenesis model. After BDL, rats were treated once daily with 25 or 50 mg/kg of WAI for 2weeks. The serum bilirubin, aspartate transaminase, alanine transaminase, malondialdehyde, and liver hydroxyproline levels were drastically increased in the BDL group. WAI administration significantly reduced these markers and restored BDL-induced depletion of glutathione content and glutathione peroxidase activity. Cholestatic liver injury and collagen deposition were markedly attenuated by WAI treatment, and these changes were paralleled by significantly suppressed gene and protein expression of fibrogenic factors, including hepatic alphasmooth muscle actin, platelet-derived growth factor, and transforming growth factor β. Our data suggest that WAI may have antifibrotic properties via both improvement of antioxidant activities and inhibition of ECM protein production in the rat model of BDL.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / genetics
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Actins / metabolism
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Animals
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Antioxidants
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Artemisia / chemistry*
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Bile Ducts / pathology*
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Bile Ducts / surgery
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Cholestasis / complications*
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Collagen Type I / genetics
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Collagen Type I / metabolism
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Collagen Type I, alpha 1 Chain
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Dose-Response Relationship, Drug
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Gene Expression / drug effects
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Hydroxyproline / chemistry
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Hydroxyproline / metabolism
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Ligation
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Liver Cirrhosis / drug therapy*
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Liver Cirrhosis / etiology
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Male
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Malondialdehyde
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Molecular Structure
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NADH, NADPH Oxidoreductases / genetics
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NADH, NADPH Oxidoreductases / metabolism
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NADPH Oxidase 1
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Plant Extracts / chemistry
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Plant Extracts / pharmacology*
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Platelet-Derived Growth Factor / genetics
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Platelet-Derived Growth Factor / metabolism
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Rats
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Rats, Sprague-Dawley
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Scopoletin / chemistry
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Specific Pathogen-Free Organisms
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / metabolism
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Actins
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Antioxidants
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Collagen Type I
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Collagen Type I, alpha 1 Chain
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Plant Extracts
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Platelet-Derived Growth Factor
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Transforming Growth Factor beta
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Tumor Necrosis Factor-alpha
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smooth muscle actin, rat
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Malondialdehyde
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NADH, NADPH Oxidoreductases
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NADPH Oxidase 1
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Scopoletin
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Hydroxyproline