Anti-inflammatory effect of resveratrol through the suppression of NF-κB and JAK/STAT signaling pathways

Acta Biochim Biophys Sin (Shanghai). 2015 Mar;47(3):207-13. doi: 10.1093/abbs/gmu135. Epub 2015 Feb 3.


Resveratrol, the most important ingredient extracted from Polygonum cuspidatum, exerts cytoprotective effects via anti-inflammatory actions in vitro. In this study, we investigated this effect of resveratrol on the lipopolysaccharide (LPS)-induced inflammatory response and its underlying molecular mechanism of action in RAW264.7 murine macrophages. Results showed that resveratrol down-regulated the expression of inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6), therefore, suppressed the production of nitric oxide and the secretion of IL-6 in LPS-stimulated RAW264.7 cells in a dose-dependent manner. Resveratrol also inhibited the translocation of high-mobility group box 1 (HMGB1) from the nucleus to the cytoplasm and of nuclear transcription factor kappa-B (NF-κB) p65 from the cytoplasm to the nucleus; it suppressed the phosphorylation of IκBα. Furthermore, these actions were mediated by suppressing the phosphorylation of signal transducer and activator of transcription (STAT)-1 and -3. In conclusion, these data indicate that resveratrol exerts anti-inflammatory effects, at least in part by reducing the release of HMGB1 and modulating the NF-κB and Janus kinase/STAT signaling pathways. Resveratrol could potentially be developed as a useful agent for the chemoprevention of inflammatory diseases.

Keywords: JAK/STAT; NF-κB; anti-inflammatory; high-mobility group box 1; resveratrol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • HMGB1 Protein / metabolism
  • I-kappa B Proteins / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Janus Kinases / metabolism
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • NF-KappaB Inhibitor alpha
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Phosphorylation / drug effects
  • RAW 264.7 Cells
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Resveratrol
  • STAT Transcription Factors / metabolism
  • Signal Transduction / drug effects*
  • Stilbenes / pharmacology*
  • Transcription Factor RelA / metabolism


  • Anti-Inflammatory Agents, Non-Steroidal
  • HMGB1 Protein
  • HMGB1 protein, mouse
  • I-kappa B Proteins
  • Interleukin-6
  • Lipopolysaccharides
  • Nfkbia protein, mouse
  • RNA, Messenger
  • Rela protein, mouse
  • STAT Transcription Factors
  • Stilbenes
  • Transcription Factor RelA
  • NF-KappaB Inhibitor alpha
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Janus Kinases
  • Resveratrol