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-T6) was stimulated with tumor necrosis factor-alpha (TNF-alpha) or transforming growth factor (TGF)-beta 1. The inhibitory effects of TP on the nuclear factor-kappa B (NF kappa B) signaling cascade and fibrosis markers, including alpha-smooth muscle actin (alpha-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 mu g/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 NF kappa B transcriptional activity induced by TNF-alpha, lipopolysaccharide and phorbol 12-myristate 13-acetate in HSC-T6 cells. In addition, TP also suppressed TNF-alpha and TGF-beta 1-induced collagen deposition and alpha-SMA secretion in HSC-T6 cells. In vivo, TP treatment significantly reduced hepatic fibrosis scores, collagen contents, IL-6 and TNF-alpha levels, and the number of alpha-SMA and NF kappa B-positive cells in DMN rats. The results showed that TP exerted antifibrotic effects in both HSC-T6 cells and DMN rats. Copyright (C) 2011 John Wiley& Sons, Ltd.