Exp Mol Med.  2011 Jun;43(6):341-349. 10.3858/emm.2011.43.6.037.

Antifibrotic effects of magnesium lithospermate B on hepatic stellate cells and thioacetamide-induced cirrhotic rats

• Paik YH
• Yoon YJ
• Lee HC
• Jung MK
• Kang SH
• Chung SI
• Kim JK
• Cho JY
• Lee KS
• Han KH

• KMID: 1107375
• DOI: http://doi.org/10.3858/emm.2011.43.6.037

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 alpha-smooth muscle actin (alpha-SMA), TGF-beta1, and collagen alpha1(I) was significantly decreased in TAA + MLB group as compared to TAA only group. Incubation with HSCs and MLB (> or =100 microM) for up to 48 h showed no cytotoxicity. MLB suppressed PDGF-induced HSC proliferation. MLB inhibited NF-kappaB transcriptional activation and monocyte chemotactic protein 1 (MCP-1) production in HSCs. MLB strongly suppressed H2O2-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.

Keyword

liver cirrhosis; Salvia miltiorrhiza; hepatic stellate cells; lithospermate B; reactive oxygen species

MeSH Terms

Actins/genetics/metabolism
Animals
Antioxidants/*administration & dosage
Cell Proliferation/drug effects
Collagen Type I/genetics/metabolism
Drugs, Chinese Herbal/*administration & dosage
Fibrosis/prevention & control
Hepatic Stellate Cells/*drug effects/metabolism/pathology
Liver/*drug effects/metabolism/pathology
Liver Cirrhosis, Experimental/chemically induced/*drug therapy/physiopathology
Male
NF-kappa B/metabolism
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species/metabolism
Salvia miltiorrhiza/immunology
Thioacetamide/administration & dosage
Transcriptional Activation/drug effects