title: Inhibition of matrix metalloproteinases and inducible nitric oxide synthase by andrographolide in human osteoarthritic chondrocytes.
abstract: OBJECTIVE
  The aim of this study was to investigate the effects of andrographolide on matrix metalloproteinases (MMP) 1, 3, and 13 and inducible nitric oxide synthase (iNOS) in human articular chondrocytes from osteoarthritic cartilage.
  
  
  METHODS
  Passaged chondrocytes were pretreated with or without andrographolide for 2 h, followed by coincubation with interleukin-1 beta (IL-1β) 1 ng/ml for 24 h. Expression levels of MMP-1, 3, and 13, tissue inhibitor of metalloproteinase-1 (TIMP-1), and iNOS were evaluated using real-time-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting. Nitric oxide (NO) was analyzed using the Griess reaction assay. Involvement of nuclear factor kappa B (NF-κB) was assessed by Western blotting, transient transfection, and luciferase reporter assay.
  
  
  RESULTS
  Andrographolide tested in these in vitro studies was found be an effective antiarthritic agent, as evidenced by potent inhibition of MMP-1, 3, and 13 and iNOS expression, as well as upregulation of TIMP-1 in IL-1β-stimulated human articular chondrocytes (p < 0.05). The mechanism of andrographolide's inhibitory effects was mediated by attenuating the activation of NF-κB in human chondrocytes in the presence of IL-1β.
  
  
  CONCLUSIONS
  Andrographolide was a potent inhibitor of the production of inflammatory and catabolic mediators by chondrocytes, suggesting that this natural compound may merit consideration as a therapeutic agent for treating and preventing osteoarthritis.
authors.affiliation: Department of Orthopedic Surgery, The Second Affiliated Hospital of School of Medicine, Zhejiang University, Jie Fang Road 88#, 310009, Hangzhou, People's Republic of China.
authors.forename: Qian-hai
authors.initials: QH
authors.lastname: Ding
authors.forename: Xiao-wei
authors.initials: XW
authors.lastname: Ji
authors.forename: Ye
authors.initials: Y
authors.lastname: Cheng
authors.forename: Yuan-quan
authors.initials: YQ
authors.lastname: Yu
authors.forename: Yi-ying
authors.initials: YY
authors.lastname: Qi
authors.forename: Xiang-hua
authors.initials: XH
authors.lastname: Wang
mesh_terms: D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D020370:Osteoarthritis, Knee / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
chemical_list: D004224:Diterpenes; D004791:Enzyme Inhibitors; D053583:Interleukin-1beta; D061965:Matrix Metalloproteinase Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; C030419:andrographolide; D052247:Nitric Oxide Synthase Type II; D020782:Matrix Metalloproteinases