title: Monascus purpureus-fermented rice inhibits tumor necrosis factor-α-induced upregulation of matrix metalloproteinase 2 and 9 in human aortic smooth muscle cells.
abstract: OBJECTIVE
  Inflammation is associated with atherosclerosis. Cholestin (Monascus purpureus-fermented rice) contains a naturally occurring statin, which has lipid-modulating, anti-inflammatory and antioxidative effects. This study aimed to investigate the effects of Cholestin extract on the expression of matrix metalloproteinase (MMP)-2 and MMP-9 by tumor necrosis factor (TNF)-α-treated human aortic smooth muscle cells (HASMCs).
  
  
  METHODS
  Zymography, reverse transcription polymerase chain reaction and immunoblot analyses were used for analysis of MMP expression of TNF-α-stimulated HASMCs. Gel shift assay was used for analysis of transcription factor nuclear factor-κB (NF-κB) activation. Intracellular reactive oxygen species (ROS) generation was also analysed.
  
  
  RESULTS
  The supplement of HASMCs with Cholestin extract significantly suppresses enzymatic activities of MMP-2 and MMP-9 in TNF-α-stimulated HASMCs. RT-PCR and immunoblot analyses show that Cholestin extract significantly attenuates TNF-α-induced mRNA and protein expressions of MMP-2 and MMP-9. Gel shift assays show that Cholestin treatment reduces TNF-α-activated NF-κB. Furthermore, Cholestin also attenuates intracellular ROS generation in TNF-α-treated HASMCs. The supplement with an ROS scavenger N-acetyl-cysteine (glutathione precursor) gives similar results to Cholestin.
  
  
  CONCLUSIONS
  Cholestin reduces TNF-α-stimulated MMP-2 and MMP-9 expression as well as downregulating NF-κB activation and intracellular ROS formation in HASMCs, supporting the notion that the natural compound Cholestin may have potential application in clinical atherosclerosis disease.
authors: Department of Pathology and Laboratory Medicine, Division of General, Laboratory, Taipei Veterans General Hospital, Institute of Biotechnology in Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Chih-Pei
authors: CP
authors: Lin
authors: Po-Hsun
authors: PH
authors: Huang
authors: Hui-Szu
authors: HS
authors: Tsai
authors: Tao-Cheng
authors: TC
authors: Wu
authors: Hsin-Bang
authors: HB
authors: Leu
authors: Po-Len
authors: PL
authors: Liu
authors: Yung-Hsiang
authors: YH
authors: Chen
mesh_terms: D001013:Aorta, Thoracic / Q000166:cytology; D050197:Atherosclerosis / Q000473:pathology; D001485:Basement Membrane / Q000166:cytology / Q000187:drug effects; D001688:Biological Products / Q000737:chemistry / Q000627:therapeutic use*; D015153:Blotting, Western; D002478:Cells, Cultured; D004396:Coloring Agents; D024202:Electrophoretic Mobility Shift Assay; D005109:Extracellular Matrix / Q000187:drug effects / Q000201:enzymology; D006083:Graft Occlusion, Vascular / Q000473:pathology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology*; D016133:Polymerase Chain Reaction; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D001688:Biological Products; D004396:Coloring Agents; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; C117343:red yeast rice; D012313:RNA; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C022616:thiazolyl blue