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

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

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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 (≥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 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.

Original languageEnglish
Pages (from-to)341-349
Number of pages9
JournalExperimental and Molecular Medicine
Volume43
Issue number6
DOIs
Publication statusPublished - 2011 Jun

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

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    Paik, Y. H., Yoon, Y. J., Lee, H. C., Jung, M. K., Kang, S. H., Chung, S. I., Kim, J. K., Cho, J. Y., Lee, K. S., & Han, K. H. (2011). Antifibrotic effects of magnesium lithospermate B on hepatic stellate cells and thioacetamide-induced cirrhotic rats. Experimental and Molecular Medicine, 43(6), 341-349. https://doi.org/10.3858/emm.2011.43.6.037