Antifibrotic effects of magnesium lithospermate B on hepatic stellate cells and thioacetamide-induced cirrhotic rats.
10.3858/emm.2011.43.6.037
- Author:
Yong Han PAIK
1
;
Young Joon YOON
;
Hyun Chul LEE
;
Man Kil JUNG
;
So Hee KANG
;
Sook In CHUNG
;
Ja Kyung KIM
;
Jae Yong CHO
;
Kwan Sik LEE
;
Kwang Hyub HAN
Author Information
1. Department of Internal Medicine, Yonsei University College of Medicine, Seoul 120-752, Korea. gihankhys@yuhs.ac
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
liver cirrhosis;
Salvia miltiorrhiza;
hepatic stellate cells;
lithospermate B;
reactive oxygen species
- MeSH:
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
- From:Experimental & Molecular Medicine
2011;43(6):341-349
- CountryRepublic of Korea
- Language:English
-
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.
