title: Antifibrotic effects of triptolide on hepatic stellate cells and dimethylnitrosamine-intoxicated rats.
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.
authors.affiliation: Institute of Clinical Medicine, School of Medicine, National Yang Ming University, Taipei, Taiwan.
authors.forename: Lee-Won
authors.initials: LW
authors.lastname: Chong
authors.forename: Yi-Chao
authors.initials: YC
authors.lastname: Hsu
authors.forename: Yung-Tsung
authors.initials: YT
authors.lastname: Chiu
authors.forename: Kuo-Ching
authors.initials: KC
authors.lastname: Yang
authors.forename: Yi-Tsau
authors.initials: YT
authors.lastname: Huang
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D003094:Collagen / Q000378:metabolism; D004128:Dimethylnitrosamine / Q000009:adverse effects; D004224:Diterpenes / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology; D055166:Hepatic Stellate Cells / Q000187:drug effects*; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010616:Phenanthrenes / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D029757:Tripterygium / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000199:Actins; D003094:Collagen; D004128:Dimethylnitrosamine; D004224:Diterpenes; D004852:Epoxy Compounds; D015850:Interleukin-6; D016328:NF-kappa B; D010616:Phenanthrenes; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C498862:Acta2 protein, rat; C001899:triptolide