Vol.23 No.6

Original Article

Inhibition of matrix metalloproteinases and inducible nitric oxide synthase by andrographolide in human osteoarthritic chondrocytes

Authors

Qian-hai Ding1 , Xiao-wei Ji2 , Ye Cheng1 , Yuan-quan Yu3 , Yi-ying Qi1 , Xiang-hua Wang1

  • 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
  • Department of Gastroenterology, The Second Affiliated Hospital of School of Medicine, Zhejiang University, Jie Fang Road 88#, 310009 Hangzhou, People’s Republic of China
  • Department of Surgery, The Second Affiliated Hospital of School of Medicine, Zhejiang University, Jie Fang Road 88#, 310009 Hangzhou, People’s Republic of China
Received:

24 April 2012

Accepted:

27 November 2012

Published online:

15 December 2012

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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-1b) 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-jB) 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-1bstimulated human articular chondrocytes (p%ABST%.05). The mechanism of andrographolide’s inhibitory effects was mediated by attenuating the activation of NF-jB in human chondrocytes in the presence of IL-1b.
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.

Key words

Andrographolide, Inducible nitric oxide synthase, Matrix metalloproteinase, Nuclear factor kappa B, Osteoarthritis