Grape polyphenols and propolis mixture inhibits inflammatory mediator release from human leukocytes and reduces clinical scores in experimental arthritis

Phytomedicine. 2014 Feb 15;21(3):290-7. doi: 10.1016/j.phymed.2013.08.015. Epub 2013 Sep 20.


Polyphenols from red fruits and bee-derived propolis (PR) are bioactive natural products in various in vitro and in vivo models. The present study shows that hematotoxicity-free doses of grape polyphenols (GPE) and PR differentially decreased the secretion of pro-inflammatory cytokines from activated human peripheral blood leucocytes. While GPE inhibited the monocytes/macrophage response, propolis decreased both monokines and interferon γ (IFNγ) production. When used together, their distinct effects lead to the attenuation of all inflammatory mediators, as supported by a significant modulation of the transcriptomic profile of pro-inflammatory genes in human leukocytes. To enforce in vitro data, GPE+PR were tested for their ability to improve clinical scores and cachexia in chronic rat adjuvant-induced arthritis (AA). Extracts significantly reduced arthritis scores and cachexia, and this effect was more significant in animals receiving continuous low doses compared to those receiving five different high doses. Animals treated daily had significantly better clinical scores than corticoid-treated rats. Together, these findings indicate that the GPE+PR combination induces potent anti-inflammatory activity due to their complementary immune cell modulation.

Keywords: Anthocyanins; Grape polyphenols; Inflammation; Macrophage; Propolis; Rheumatoid arthritis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Apitherapy
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / metabolism
  • Cachexia / drug therapy
  • Drug Therapy, Combination
  • Female
  • Fruit
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Inflammation Mediators / metabolism*
  • Interferon-gamma / metabolism
  • Leukocytes / metabolism*
  • Monokines / metabolism
  • Phytotherapy
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Polyphenols / pharmacology
  • Polyphenols / therapeutic use*
  • Propolis / pharmacology
  • Propolis / therapeutic use*
  • Rats
  • Rats, Inbred Strains
  • Transcriptome
  • Vitis / chemistry*


  • Anti-Inflammatory Agents
  • Inflammation Mediators
  • Monokines
  • Plant Extracts
  • Polyphenols
  • Interferon-gamma
  • Propolis