PMID- 21499011 OWN - NLM STAT- MEDLINE DCOM- 20111014 LR - 20211020 IS - 2092-6413 (Electronic) IS - 1226-3613 (Print) IS - 1226-3613 (Linking) VI - 43 IP - 6 DP - 2011 Jun 30 TI - Antifibrotic effects of magnesium lithospermate B on hepatic stellate cells and thioacetamide-induced cirrhotic rats. PG - 341-9 AB - 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 muM) 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 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. FAU - Paik, Yong Han AU - Paik YH AD - Department of Internal Medicine Yonsei University College of MedicineSeoul 120-752, Korea. FAU - Yoon, Young Joon AU - Yoon YJ FAU - Lee, Hyun Chul AU - Lee HC FAU - Jung, Man Kil AU - Jung MK FAU - Kang, So Hee AU - Kang SH FAU - Chung, Sook In AU - Chung SI FAU - Kim, Ja Kyung AU - Kim JK FAU - Cho, Jae Yong AU - Cho JY FAU - Lee, Kwan Sik AU - Lee KS FAU - Han, Kwang Hyub AU - Han KH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Exp Mol Med JT - Experimental & molecular medicine JID - 9607880 RN - 0 (Actins) RN - 0 (Antioxidants) RN - 0 (Collagen Type I) RN - 0 (Drugs, Chinese Herbal) RN - 0 (NF-kappa B) RN - 0 (Reactive Oxygen Species) RN - 0 (smooth muscle actin, rat) RN - 075T165X8M (Thioacetamide) RN - 122021-74-3 (lithospermate B) SB - IM MH - Actins/genetics/metabolism MH - Animals MH - Antioxidants/*administration & dosage MH - Cell Proliferation/drug effects MH - Collagen Type I/genetics/metabolism MH - Drugs, Chinese Herbal/*administration & dosage MH - Fibrosis/prevention & control MH - Hepatic Stellate Cells/*drug effects/metabolism/pathology MH - Liver/*drug effects/metabolism/pathology MH - Liver Cirrhosis, Experimental/chemically induced/*drug therapy/physiopathology MH - Male MH - NF-kappa B/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Reactive Oxygen Species/metabolism MH - Salvia miltiorrhiza/immunology MH - Thioacetamide/administration & dosage MH - Transcriptional Activation/drug effects PMC - PMC3128912 EDAT- 2011/04/19 06:00 MHDA- 2011/10/15 06:00 PMCR- 2011/06/30 CRDT- 2011/04/19 06:00 PHST- 2011/04/19 06:00 [entrez] PHST- 2011/04/19 06:00 [pubmed] PHST- 2011/10/15 06:00 [medline] PHST- 2011/06/30 00:00 [pmc-release] AID - emm.2010.43.037 [pii] AID - 10.3858/emm.2011.43.6.037 [doi] PST - ppublish SO - Exp Mol Med. 2011 Jun 30;43(6):341-9. doi: 10.3858/emm.2011.43.6.037.