Anti-Inflammatory Effects of (3S)-Vestitol on Peritoneal Macrophages

Bruno Bueno-Silva1,2, Manuela Rocha Bueno1, Dione Kawamoto1

  • 1Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-900, SP, Brazil.

Insights

The isoflavone (3S)-vestitol from red propolis reduces inflammatory nitric oxide (NO) and cytokines in macrophages. It may help treat inflammatory diseases like atherosclerosis and periodontitis.

Area of Science:

  • Immunology
  • Pharmacology
  • Natural Products Chemistry

Background:

  • The anti-inflammatory properties of (3S)-vestitol, an isoflavone from red propolis, are known, but its precise mechanisms in macrophages remain unclear.
  • Macrophages play a crucial role in inflammatory responses, making them a key target for understanding and modulating inflammation.
  • Few studies have investigated the molecular mechanisms underlying the anti-inflammatory effects of (3S)-vestitol in macrophages.

Purpose of the Study:

  • To elucidate the anti-inflammatory mechanisms of (3S)-vestitol in lipopolysaccharide-stimulated mouse peritoneal macrophages.
  • To evaluate the impact of (3S)-vestitol on nitric oxide (NO) production, cytokine release, and gene expression in macrophages.
  • To explore the potential of (3S)-vestitol as a therapeutic agent for inflammatory conditions.

Main Methods:

  • Peritoneal macrophages from C57BL6 mice were stimulated with lipopolysaccharide and treated with varying concentrations of (3S)-vestitol (0.37–0.59 µM) for 48 hours.
  • Assays were performed to measure nitric oxide (NO) levels, macrophage viability, and the release of 20 different cytokines.
  • Gene expression analysis was conducted for genes involved in inflammation, cytokine production, and related pathways.

Main Results:

  • A concentration of 0.55 µM (V55) of (3S)-vestitol significantly reduced NO release by 60% without affecting cell viability.
  • V55 treatment diminished the levels of pro-inflammatory cytokines IL-1β, IL-1α, G-CSF, IL-10, and GM-CSF.
  • V55 modulated the expression of key genes, including downregulation of inflammation-associated genes (Icam-1, Wnt5a, Mmp7) and upregulation of inhibitory genes (Socs3, Dab2) and atherosclerosis-related genes (Apoe).

Conclusions:

  • The anti-inflammatory effects of (3S)-vestitol in macrophages involve the inhibition of cytokine release and the NF-κB pathway.
  • These findings suggest that (3S)-vestitol possesses mechanisms that could be beneficial in managing persistent inflammatory diseases.
  • (3S)-vestitol shows promise as a potential candidate for further in vivo research into the treatment or prevention of atherosclerosis and periodontitis.

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