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

Authors

  • Lee-Won Chong,

    1. Institute of Clinical Medicine, School of Medicine, National Yang Ming University, Taipei, Taiwan
    2. Division of Hepatology and Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
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  • Yi-Chao Hsu,

    1. Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan
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  • Yung-Tsung Chiu,

    1. Department of Medical Research and Education, Taichung Veterans General Hospital, Taichung, Taiwan
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  • Kuo-Ching Yang,

    1. Division of Hepatology and Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
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  • Yi-Tsau Huang

    Corresponding author
    1. Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
    2. National Research Institute of Chinese Medicine, Taipei, Taiwan
    • Institute of Clinical Medicine, School of Medicine, National Yang Ming University, Taipei, Taiwan
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Yi-Tsau Huang, Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, No. 155, Li-Nong Street, Sec. 2, Taipei 112, Taiwan.

E-mail: huangyt@ym.edu.tw

Abstract

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.

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