Antifibrotic Effects of Triptolide on Hepatic Stellate Cells and Dimethylnitrosamine-intoxicated Rats

Triptolide (C38H42O6N2, TP, a diterpene triepoxide derived from Tripterygium wilfordii Hook F.), is a potent immunosuppresive and antiinflammatory agent. The present study investigated whether TP exerted antihepatofibrotic effects in vitro and in vivo. A cell line of rat hepatic stellate cells (HSC‐...

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Published in:Phytotherapy research Vol. 25; no. 7; pp. 990 - 999
Main Authors: Chong, Lee-Won, Hsu, Yi-Chao, Chiu, Yung-Tsung, Yang, Kuo-Ching, Huang, Yi-Tsau
Format: Journal Article
Language:English
Published: Chichester, UK John Wiley & Sons, Ltd 01-07-2011
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Summary:Triptolide (C38H42O6N2, TP, a diterpene triepoxide derived from Tripterygium wilfordii Hook F.), is a potent immunosuppresive and antiinflammatory agent. The present study investigated whether TP exerted antihepatofibrotic effects in vitro and in vivo. A cell line of rat hepatic stellate cells (HSC‐T6) was stimulated with tumor necrosis factor‐α (TNF‐α) or transforming growth factor (TGF)‐β1. The inhibitory effects of TP on the nuclear factor‐κB (NFκB) signaling cascade and fibrosis markers, including α‐smooth muscle actin (α‐SMA) and collagen, were assessed. An in vivo therapeutic study was conducted in dimethylnitrosamine (DMN)‐treated rats. The rats were randomly assigned to one of three groups: control rats, DMN rats receiving vehicle only and DMN rats receiving TP (20 μg/kg). Treatment was given by gavage twice daily for 3 weeks starting 1 week after the start of DMN administration. TP (5–100 nm) concentration‐dependently inhibited the NFκB transcriptional activity induced by TNF‐α, lipopolysaccharide and phorbol 12‐myristate 13‐acetate in HSC‐T6 cells. In addition, TP also suppressed TNF‐α and TGF‐β1‐induced collagen deposition and α‐SMA secretion in HSC‐T6 cells. In vivo, TP treatment significantly reduced hepatic fibrosis scores, collagen contents, IL‐6 and TNF‐α levels, and the number of α‐SMA and NFκB‐positive cells in DMN rats. The results showed that TP exerted antifibrotic effects in both HSC‐T6 cells and DMN rats. Copyright © 2011 John Wiley & Sons, Ltd.
Bibliography:National Research Institute of Chinese Medicine - No. NRICM99-DBCM-05
istex:3C1DF245BE54825FCD37501637966D4C26B224B1
Shin Kong Wu Ho-Su Memorial Hospital Research Program - No. SKH-8302-96-DR-08
National Science Council - No. NSC 96-2320-B-010-015-MY3
ark:/67375/WNG-2S795ML9-4
ArticleID:PTR3381
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0951-418X
1099-1573
DOI:10.1002/ptr.3381