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

Authors
 Yong-Han Paik  ;  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 
Citation
 EXPERIMENTAL AND MOLECULAR MEDICINE, Vol.43(6) : 341-349, 2011 
Journal Title
EXPERIMENTAL AND MOLECULAR MEDICINE
ISSN
 1226-3613 
Issue Date
2011
MeSH
Actins/genetics ; Actins/metabolism ; Animals ; Antioxidants/administration & dosage* ; Cell Proliferation/drugeffects ; Collagen Type I/genetics ; Collagen Type I/metabolism ; Drugs, Chinese Herbal/administration & dosage* ; Fibrosis/prevention & control ; HepaticStellateCells/drugeffects* ; HepaticStellateCells/metabolism ; HepaticStellateCells/pathology ; Liver/drugeffects* ; Liver/metabolism ; Liver/pathology ; Liver Cirrhosis, Experimental/chemically induced ; Liver Cirrhosis, Experimental/drug therapy* ; Liver Cirrhosis, Experimental/physiopathology ; Male ; NF-kappaB/metabolism ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species/metabolism ; Salvia miltiorrhiza/immunology ; Thioacetamide/administration & dosage ; Transcriptional Activation/drugeffects
Keywords
antifibrotic therapy ; collagen ; hepatic fibrosis ; hepatic stellate cell ; magnesium lithospermate B ; reactive oxygen species
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.
Files in This Item:
T201103450.pdf Download
DOI
10.3858/emm.2011.43.6.037
Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Ja Kyung(김자경) ORCID logo https://orcid.org/0000-0001-5025-6846
Paik, Yong Han(백용한)
Yoon, Young Joon(윤영준)
Lee, Kwan Sik(이관식) ORCID logo https://orcid.org/0000-0002-3672-1198
Lee, Hyun Chul(이현철)
Chung, Sook In(정숙인) ORCID logo https://orcid.org/0000-0002-7915-9203
Cho, Jae Yong(조재용) ORCID logo https://orcid.org/0000-0002-0926-1819
Han, Kwang-Hyub(한광협) ORCID logo https://orcid.org/0000-0003-3960-6539
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/94336
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