Resveratrol Suppresses TNF-Induced Activation of Nuclear Transcription Factors NF-κB, Activator Protein-1, and Apoptosis: Potential Role of Reactive Oxygen Intermediates and Lipid Peroxidation

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207

作者：

SK Manna，A Mukhopadhyay，BB Aggarwal

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摘要：

Resveratrol (trans-3,4′,5-trihydroxystilbene), a polyphenolic phytoalexin found in grapes, fruits, and root extracts of the weed Polygonum cuspidatum, exhibits anti-inflammatory, cell growth-modulatory, and anticarcinogenic effects. How this chemical produces these effects is not known, but it may work by suppressing NF-κB, a nuclear transcription factor that regulates the expression of various genes involved in inflammation, cytoprotection, and carcinogenesis. In this study, we investigated the effect of resveratrol on NF-κB activation induced by various inflammatory agents. Resveratrol blocked TNF-induced activation of NF-κB in a dose- and time-dependent manner. Resveratrol also suppressed TNF-induced phosphorylation and nuclear translocation of the p65 subunit of NF-κB, and NF-κB-dependent reporter gene transcription. Suppression of TNF-induced NF-κB activation by resveratrol was not restricted to myeloid cells (U-937); it was also observed in lymphoid (Jurkat) and epithelial (HeLa and H4) cells. Resveratrol also blocked NF-κB activation induced by PMA, LPS, H2O2, okadaic acid, and ceramide. The suppression of NF-κB coincided with suppression of AP-1. Resveratrol also inhibited the TNF-induced activation of mitogen-activated protein kinase kinase and c-Jun N-terminal kinase and abrogated TNF-induced cytotoxicity and caspase activation. Both reactive oxygen intermediate generation and lipid peroxidation induced by TNF were suppressed by resveratrol. Resveratrol's anticarcinogenic, anti-inflammatory, and growth-modulatory effects may thus be partially ascribed to the inhibition of activation of NF-κB and AP-1 and the associated kinases.

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关键词：

antiinflammatory agents antineoplastic agents cell cultures cells foods fruits grapes inflammation resveratrol transcription factors