title: Inhibitory effect of tanshinone IIA on rat hepatic stellate cells.
abstract: BACKGROUND
  Anti-inflammation via inhibition of NF-κB pathways in hepatic stellate cells (HSCs) is one therapeutic approach to hepatic fibrosis. Tanshinone IIA (C19H18O3, Tan IIA) is a lipophilic diterpene isolated from Salvia miltiorrhiza Bunge, with reported anti-inflammatory activity. We tested whether Tan IIA could inhibit HSC activation.
  
  
  METHODS
  The cell line of rat hepatic stellate cells (HSC-T6) was stimulated with lipopolysaccharide (LPS) (100 ng/ml). Cytotoxicity was assessed by MTT assay. HSC-T6 cells were pretreated with Tan IIA (1, 3 and 10 µM), then induced by LPS (100 ng/ml). NF-κB activity was evaluated by the luciferase reporter gene assay. Western blotting analysis was performed to measure NF-κB-p65, and phosphorylations of MAPKs (ERK, JNK, p38). Cell chemotaxis was assessed by both wound-healing assay and trans-well invasion assay. Quantitative real-time PCR was used to detect gene expression in HSC-T6 cells.
  
  
  RESULTS
  All concentrations of drugs showed no cytotoxicity against HSC-T6 cells. LPS stimulated NF-κB luciferase activities, nuclear translocation of NF-κB-p65, and phosphorylations of ERK, JNK and p38, all of which were suppressed by Tan IIA. In addition, Tan IIA significantly inhibited LPS-induced HSCs chemotaxis, in both wound-healing and trans-well invasion assays. Moreover, Tan IIA attenuated LPS-induced mRNA expressions of CCL2, CCL3, CCL5, IL-1β, TNF-α, IL-6, ICAM-1, iNOS, and α-SMA in HSC-T6 cells.
  
  
  CONCLUSIONS
  Our results demonstrated that Tan IIA decreased LPS-induced HSC activation.
authors: Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Ya-Wei
authors: YW
authors: Liu
authors: Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan.
authors: Yi-Tsau
authors: YT
authors: Huang
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000199:Actins / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002461:Cell Line, Transformed; D002633:Chemotaxis / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats
chemical_list: D045784:Abietanes; D000199:Actins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D016328:NF-kappa B; C021751:tanshinone; D020928:Mitogen-Activated Protein Kinases