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Antifibrotic Effects of Triptolide on Hepatic Stellate Cells and Dimethylnitrosamine‐intoxicated Rats
Author(s) -
Chong LeeWon,
Hsu YiChao,
Chiu YungTsung,
Yang KuoChing,
Huang YiTsau
Publication year - 2011
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.3381
Subject(s) - hepatic stellate cell , in vivo , triptolide , tumor necrosis factor alpha , hepatic fibrosis , phorbol , medicine , endocrinology , chemistry , tripterygium wilfordii , nf κb , pharmacology , in vitro , transforming growth factor , fibrosis , lipopolysaccharide , inflammation , biology , signal transduction , biochemistry , pathology , apoptosis , alternative medicine , microbiology and biotechnology , protein kinase c
Triptolide (C 38 H 42 O 6 N 2 , 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 i n 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 n m ) 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.