Antifibrotic effects of triptolide on hepatic stellate cells and dimethylnitrosamine-intoxicated rats

Phytother Res. 2011 Jul;25(7):990-9. doi: 10.1002/ptr.3381.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Cell Line
  • Collagen / metabolism
  • Dimethylnitrosamine / adverse effects
  • Diterpenes / pharmacology*
  • Epoxy Compounds / pharmacology
  • Hepatic Stellate Cells / drug effects*
  • Interleukin-6 / metabolism
  • Liver / drug effects
  • Liver / pathology
  • Liver Cirrhosis, Experimental / drug therapy*
  • Liver Cirrhosis, Experimental / pathology
  • Male
  • NF-kappa B / metabolism
  • Phenanthrenes / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Transforming Growth Factor beta1 / pharmacology
  • Tripterygium / chemistry
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Actins
  • Diterpenes
  • Epoxy Compounds
  • Interleukin-6
  • NF-kappa B
  • Phenanthrenes
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha
  • smooth muscle actin, rat
  • triptolide
  • Collagen
  • Dimethylnitrosamine