title: Antifibrotic effects of magnesium lithospermate B on hepatic stellate cells and thioacetamide-induced cirrhotic rats.
abstract: Magnesium lithospermate B (MLB) is one of the major active components of Salvia miltiorrhizae. The anti-oxidative effects of Salvia miltiorrhizae have been previously reported. The aim of this study was to investigate the effect of purified MLB on hepatic fibrosis in rats and on the fibrogenic responses in hepatic stellate cells (HSCs). Hepatic fibrosis was induced in rats by intraperitoneal thioacetamide (TAA) injections over a period of 8 or 12 weeks. MLB was orally administered daily by gavage tube. Serum AST and ALT levels in TAA+ MLB group were significantly lower than those in TAA only group at week 8. Hepatic fibrosis was significantly attenuated in TAA+MLB group than in TAA only group at week 8 or 12. Activation of HSCs was also decreased in TAA+MLB group as compared to TAA only group. Hepatic mRNA expression of α-smooth muscle actin (α-SMA), TGF-β1, and collagen α1(I) was significantly decreased in TAA+MLB group as compared to TAA only group. Incubation with HSCs and MLB (>or=100 μM) for up to 48 h showed no cytotoxicity. MLB suppressed PDGF-induced HSC proliferation. MLB inhibited NF-ΚB transcriptional activation and monocyte chemotactic protein 1 (MCP-1) production in HSCs. MLB strongly suppressed H(2)O(2)-induced reactive oxygen species (ROS) generation in HSCs, and MLB inhibited type I collagen secretion in HSCs. We concluded that MLB has potent antifibrotic effect in TAA-treated cirrhotic rats, and inhibits fibrogenic responses in HSCs. These data suggest that MLB has potential as a novel therapy for hepatic fibrosis.
authors.affiliation: Department of Internal Medicine Yonsei University College of MedicineSeoul 120-752, Korea.
authors.forename: Yong Han
authors.initials: YH
authors.lastname: Paik
authors.forename: Young Joon
authors.initials: YJ
authors.lastname: Yoon
authors.forename: Hyun Chul
authors.initials: HC
authors.lastname: Lee
authors.forename: Man Kil
authors.initials: MK
authors.lastname: Jung
authors.forename: So Hee
authors.initials: SH
authors.lastname: Kang
authors.forename: Sook In
authors.initials: SI
authors.lastname: Chung
authors.forename: Ja Kyung
authors.initials: JK
authors.lastname: Kim
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Cho
authors.forename: Kwan Sik
authors.initials: KS
authors.lastname: Lee
authors.forename: Kwang Hyub
authors.initials: KH
authors.lastname: Han
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D005355:Fibrosis / Q000517:prevention & control; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D027561:Salvia miltiorrhiza / Q000276:immunology; D013853:Thioacetamide / Q000008:administration & dosage; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D000199:Actins; D000975:Antioxidants; D024042:Collagen Type I; D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D013853:Thioacetamide; C498862:Acta2 protein, rat; C061091:lithospermate B