Synergistic chondroprotective effects of curcumin and resveratrol in human articular chondrocytes: inhibition of interleukin-1beta-induced nuclear factor-kappaB-mediated inflammation and apoptosis
IntroductionCurrently available treatments for osteoarthritis (OA) are restricted to non-steroidal anti-inflammatory drugs (NSAIDs), 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 nuclear factor-kappaB (NF-kappaB) signalling pathway.
Methods: We have recently demonstrated that in chondrocytes resveratrol modulates the NF-kappaB pathway by inhibiting the proteasome, while curcumin modulates the activation of NF-kappaB 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 interleukin (IL)-1beta-stimulated human chondrocytes in vitro using immunoblotting and electron microscopy.
Results: Treatment with curcumin and resveratrol suppressed NF-kappaB regulated gene products involved in inflammation (cyclooxygenase-2 (COX-2) and matrix metalloproteinase (MMP)-3, -9, vascular endothelial growth factor (VEGF)), inhibited apoptosis (Bcl-2, Bcl-xL, and tumor necrosis factor receptor-associated factor 1 (TRAF1)) and prevented activation of caspase-3.
IL-1beta-induced NF-kappaB activation was suppressed directly by cocktails of curcumin and resveratrol through inhibition of Ikappakappa- and proteasome-activation, inhibition of Ikappa-Balpha phosphorylation and degradation and inhibition of nuclear translocation of NF-kappaB. The modulatory effects of curcumin and resveratrol on IL-1beta-induced expression of cartilage-specific matrix and pro-inflammatory enzymes are 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 to separate treatment with each individual compound.
Author: Constanze CsakiAli MobasheriMehdi Shakibaei
Credits/Source: Arthritis Research &Therapy 2009, 11:R165
Published on: 2009-11-04
Copyright by the authors listed above - made available via BioMedCentral (Open Access). Please
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