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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.
Abstract:
The isoflavone (3S)-vestitol, obtained from red propolis, has exhibited anti-inflammatory, antimicrobial, and anti-caries activity; however, few manuscripts deal with its anti-inflammatory mechanisms in macrophages. The objective is to elucidate the anti-inflammatory mechanisms of (3S)-vestitol on those cells. Peritoneal macrophages of C57BL6 mice, stimulated with lipopolysaccharide, were treated with 0.37 to 0.59 µM of (3S)-vestitol for 48 h. Then, nitric oxide (NO) quantities, macrophages viability, the release of 20 cytokines and the transcription of several genes related to cytokine production and inflammatory response were evaluated. The Tukey-Kramer variance analysis test statistically analyzed the data. (3S)-vestitol 0.55 µM (V55) lowered NO release by 60% without altering cell viability and diminished IL-1β, IL-1α, G-CSF, IL-10 and GM-CSF levels. V55 reduced expression of Icam-1, Wnt5a and Mmp7 (associated to inflammation and tissue destruction in periodontitis) and Scd1, Scd2, Egf1 (correlated to atherosclerosis). V55 increased expression of Socs3 and Dab2 genes (inhibitors of cytokine signaling and NF-κB pathway), Apoe (associated to atherosclerosis control), Igf1 (encoder a protein with analogous effects to insulin) and Fgf10 (fibroblasts growth factor). (3S)-vestitol anti-inflammatory mechanisms involve cytokines and NF-κB pathway inhibition. Moreover, (3S)-vestitol may be a candidate for future in vivo investigations about the treatment/prevention of persistent inflammatory diseases such as atherosclerosis and periodontitis.
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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