title: Salvianolic Acid B Down-regulates Matrix Metalloproteinase-9 Activity and Expression in Tumor Necrosis Factor-α-induced Human Coronary Artery Endothelial Cells.
abstract: BACKGROUND
  Salvianolic acid B (Sal B) is a bioactive water-soluble compound of Salviae miltiorrhizae, a traditional herbal medicine that has been used clinically for the treatment of cardiovascular diseases. This study sought to evaluate the effect of Sal B on matrix metalloproteinase-9 (MMP-9) and on the underlying mechanisms in tumor necrosis factor-α± (TNF-α±)-activated human coronary artery endothelial cells (HCAECs), a cell model of Kawasaki disease.
  
  
  METHODS
  HCAECs were pretreated with 1-10 αμmol/L of Sal B, and then stimulated by TNF-α± at different time points. The protein expression and activity of MMP-9 were determined by Western blot assay and gelatin zymogram assay, respectively. Nuclear factor-κB (NF-κB) activation was detected with immunofluorescence, electrophoretic mobility shift assay, and Western blot assay. Protein expression levels of mitogen-activated protein kinase (c-Jun N-terminal kinase [JNK], extra-cellular signal-regulated kinase [ERK], and p38) were determined by Western blot assay.
  
  
  RESULTS
  After HCAECs were exposed to TNF-α±, 1-10 αμmol/L Sal B significantly inhibited TNF-α±-induced MMP-9 expression and activity. Furthermore, Sal B significantly decreased IκBα± phosphorylation and p65 nuclear translocation in HCAECs stimulated with TNF-α± for 30 min. In addition, Sal B decreased the phosphorylation of JNK and ERK1/2 proteins in cells treated with TNF-α± for 10 min.
  
  
  CONCLUSIONS
  The data suggested that Sal B suppressed TNF-α±-induced MMP-9 expression and activity by blocking the activation of NF-κB, JNK, and ERK1/2 signaling pathways.
authors.forename: Le
authors.initials: L
authors.lastname: Ma
authors.forename: Yun-Qian
authors.initials: YQ
authors.lastname: Guan
authors.affiliation: Department of Pediatrics, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China.
authors.forename: Zhong-Dong
authors.initials: ZD
authors.lastname: Du
mesh_terms: D001572:Benzofurans / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003331:Coronary Vessels / Q000166:cytology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D053630:Depsides
chemical_list: D001572:Benzofurans; D020780:Matrix Metalloproteinase 9; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C076944:salvianolic acid B; D053630:Depsides