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Title:
Synergistic chondroprotective effects of curcumin and resveratrol in human articular chondrocytes: inhibition of IL-1β-induced NF-κB-mediated inflammation and apoptosis | Arthritis Research & Therapy
Description:
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.
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Keywords {🔍}
curcumin, resveratrol, chondrocytes, ilβ, pubmed, nfκb, article, google, scholar, cas, hours, figure, ilβinduced, human, effects, activation, cell, expression, ngml, apoptosis, iκbα, sox, inhibition, cells, primary, cultures, protein, factor, gene, nuclear, minutes, panel, treatment, chondrocyte, antibodies, degradation, collagen, type, pretreated, products, cartilage, effect, articular, transcription, matrix, cotreated, inhibited, mmp, authors, analysis,
Topics {✒️}
n-ac-leu-leu-norleucinal apaap 100 μm n-ac-leu-leu-norleucinal il-1β-induced nf-κb-dependent proinflammatory il-1β-induced nf-κb-dependent expression il-1β-induced nf-κb-mediated inflammation c-jun n-terminal kinase il-1β-induced nf-κb activation il-1β-induced gene products nf-κb-regulated gene products nf-κb-specific gene products stabilized il-1β-induced ubiquitination inhibit il-1β-induced activation proteasome-induced nf-κb pathway nuclear factor-κb-regulated antiapoptotic counteract il-1β-induced apoptosis rel/nf-κb transcription factors nf-κb-regulated gene expression interleukin-1β-induced chondrocytes injury il-1β-induced nuclear translocation il-1β-induced ikk activation il-1β-mediated cellular responses inhibit il-1β-induced apoptosis cell-specific nf-κb inhibitor nuclear factor-kappab signaling il-1β-induced iκbα ubiquitination il-1β-induced iκbα degradation il-1β-stimulated chondrogenic inhibition il-1β-stimulated human chondrocytes nf-κb signaling pathways article download pdf il-1β-induced cytotoxicity il-1β-stimulated primary chondrocytes il-1β-induced activation il-1β-dependent iκbα phosphorylation anti-apoptotic gene products pro-apoptotic gene production il-1β-stimulated chondrocytes showed specific nf-κb inhibitor il-1β-induced mitochondrial matrix-degrading gene products nf-κb signalling pathway il-1β-induced decrease inhibit nf-κb activation transcription factor nf-κb il-1β-induced downregulation il-1β-induced reduction housekeeping protein β-actin nuclear nf-κb staining il-1β-induced suppression il-1β-induced expression
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- Aziz MH, Reagan-Shaw S, Wu J, Longley BJ, Ahmad N: Chemoprevention of skin cancer by grape constituent resveratrol: relevance to human disease?
- Brennan FM, Maini RN, Feldmann M: TNF alpha - a pivotal role in rheumatoid arthritis?
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headline:Synergistic chondroprotective effects of curcumin and resveratrol in human articular chondrocytes: inhibition of IL-1β-induced NF-κB-mediated inflammation and apoptosis
description: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. 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. 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. We propose that combining these natural compounds may be a useful strategy in OA therapy as compared with separate treatment with each individual compound.
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Human Chondrocytes
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Rheumatology
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headline:Synergistic chondroprotective effects of curcumin and resveratrol in human articular chondrocytes: inhibition of IL-1β-induced NF-κB-mediated inflammation and apoptosis
description: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. 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. 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. We propose that combining these natural compounds may be a useful strategy in OA therapy as compared with separate treatment with each individual compound.
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Resveratrol
Human Chondrocytes
ALLN
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Rheumatology
Orthopedics
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