Synergistic chondroprotective effects of curcumin and resveratrol in human articular chondrocytes: inhibition of IL-1 beta-induced NF-kappa B-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.