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Open Access Highly Accessed Research article

Synergistic chondroprotective effects of curcumin and resveratrol in human articular chondrocytes: inhibition of IL-1β-induced NF-κB-mediated inflammation and apoptosis

Constanze Csaki1, Ali Mobasheri2 and Mehdi Shakibaei1*

Author Affiliations

1 Musculoskeletal Research Group, Institute of Anatomy, Ludwig-Maximilians-University Munich, Pettenkoferstrasse 11, 80336 Munich, Germany

2 Musculoskeletal Research Group, Division of Veterinary Medicine, School of Veterinary Medicine and Science, Faculty of Medicine and Health Sciences, University of Nottingham, Sutton Bonington Campus, Sutton Bonington LE12 5RD, UK

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Arthritis Research & Therapy 2009, 11:R165  doi:10.1186/ar2850

Published: 4 November 2009

Abstract

Introduction

Currently available treatments for osteoarthritis (OA) are restricted to nonsteroidal anti-inflammatory drugs, which exhibit numerous side effects and are only temporarily effective. Thus novel, safe and more efficacious anti-inflammatory agents are needed for OA. Naturally occurring polyphenolic compounds, such as curcumin and resveratrol, are potent agents for modulating inflammation. Both compounds mediate their effects by targeting the NF-κB signalling pathway.

Methods

We have recently demonstrated that in chondrocytes resveratrol modulates the NF-κB pathway by inhibiting the proteasome, while curcumin modulates the activation of NF-κB by inhibiting upstream kinases (Akt). However, the combinational effects of these compounds in chondrocytes has not been studied and/or compared with their individual effects. The aim of this study was to investigate the potential synergistic effects of curcumin and resveratrol on IL-1β-stimulated human chondrocytes in vitro using immunoblotting and electron microscopy.

Results

Treatment with curcumin and resveratrol suppressed NF-κB-regulated gene products involved in inflammation (cyclooxygenase-2, matrix metalloproteinase (MMP)-3, MMP-9, vascular endothelial growth factor), inhibited apoptosis (Bcl-2, Bcl-xL, and TNF-α receptor-associated factor 1) and prevented activation of caspase-3. IL-1β-induced NF-κB activation was suppressed directly by cocktails of curcumin and resveratrol through inhibition of Iκκ and proteasome activation, inhibition of IκBα phosphorylation and degradation, and inhibition of nuclear translocation of NF-κB. The modulatory effects of curcumin and resveratrol on IL-1β-induced expression of cartilage specific matrix and proinflammatory enzymes were mediated in part by the cartilage-specific transcription factor Sox-9.

Conclusions

We propose that combining these natural compounds may be a useful strategy in OA therapy as compared with separate treatment with each individual compound.