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

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-kappa B signalling pathway. Methods We have recently demonstrated that in chondrocytes resveratrol modulates the NF-kappa B pathway by inhibiting the proteasome, while curcumin modulates the activation of NF-kappa B 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-1 beta-stimulated human chondrocytes in vitro using immunoblotting and electron microscopy. Results Treatment with curcumin and resveratrol suppressed NF-kappa B-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-alpha receptor-associated factor 1) and prevented activation of caspase-3. IL-1 beta-induced NF-kappa B activation was suppressed directly by cocktails of curcumin and resveratrol through inhibition of I kappa kappa and proteasome activation, inhibition of I kappa B alpha phosphorylation and degradation, and inhibition of nuclear translocation of NF-kappa B. The modulatory effects of curcumin and resveratrol on IL-1 beta-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.