title: Tetramethylpyrazine Inhibits Activation of Hepatic Stellate Cells through Hedgehog Signaling Pathways In Vitro.
abstract: OBJECTIVE
  Tetramethylpyrazine (TMP), a major alkaloid isolated from Ligusticum chuanxiong, has been reported in hepatic fibrosis models. However, the action mechanism remains unclear. In the present study, effects of tetramethylpyrazine (TMP) against hepatic stellate cell (HSC) activation as well as the possible mechanisms were evaluated.
  
  
  METHODS
  Western blot assay was used to detect TMP effects on protein expression of Smo, Patched, Hhip, and Gli and to investigate the effects of TMP on Cyclin D1, Cyclin E1, CDK2, Bcl-2, Bax, and caspase expression with cyclopamine supplementation.
  
  
  RESULTS
  Our results showed that TMP significantly inhibits the expression of Cyclin D1, Cyclin E1, and Cyclin-dependent kinase CDK2 and changes the HSC cycle by inhibiting the proliferation of HSC. Moreover, TMP has also been shown to decrease the expression of Bcl-2 and increase the expression of Bax in HSC-T6 cells. Furthermore, TMP can inhibit the expression of connective tissue growth factor (CTGF), and the inhibitory effect was intensified after the application of joint treatment with TMP and cyclopamine.
  
  
  CONCLUSIONS
  TMP may be an effective Hh signaling pathway inhibitor for hepatic fibrosis treatment.
authors.affiliation: Zhejiang Medical College, Hangzhou 310053, China.
authors.forename: Jue
authors.initials: J
authors.lastname: Hu
authors.affiliation: Research Center of TCM Processing Technology, Zhejiang Chinese Medical University, Hangzhou 311401, China ; Department of Chinese Materia Medica, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Cao
authors.affiliation: Research Center of TCM Processing Technology, Zhejiang Chinese Medical University, Hangzhou 311401, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Chinese Materia Medica, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of Chinese Materia Medica, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Baochang
authors.initials: B
authors.lastname: Cai
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects; D030342:Genetic Diseases, Inborn / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011719:Pyrazines / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C526317:CCN2 protein, human; D053823:Hedgehog Proteins; D011719:Pyrazines; D055513:Connective Tissue Growth Factor; D018844:Cyclin-Dependent Kinases; C017953:tetramethylpyrazine