Previously, we demonstrated the anti-inflammatory properties of vestitol in a neutrophil model. Here, we show the effects of vestitol on macrophage activation and function. Vestitol was obtained from Brazilian red propolis after bioguided fractionation and tested at different concentrations in LPS-activated RAW 264.7 murine macrophages for nitric oxide (NO) production and cell viability. The levels of TNF-α, IL1-β, TGF-β, IL-4, IL-6, IL-10, IL-12, GM-CSF, IFN-ɣ and gene expression related to cytokines, NO, PI3K-AKT and signal transduction pathways were assayed by ELISA and RT-qPCR, respectively. Differences were determined by one-way ANOVA followed by Tukey-Kramer. Vestitol inhibited NO production by 83% at 0.55 μM without affecting cell viability when compared to the vehicle control (P < 0.05). Treatment with vestitol reduced GM-CSF, IL-6, TNF-α, IL-4 and TGF-β levels and increased IL-10 release (P < 0.05). Vestitol affected the expression of genes related to NF-κB pathway, NO synthase, and inhibition of leukocyte transmigration, namely: Ccs, Ccng1, Calm1, Tnfsf15, Il11, Gata3, Gadd45b, Cdkn1b, Csf1, Ccl5, Birc3 (negatively regulated), and Igf1 (positively regulated). Vestitol diminished the activation of NF-κB and Erk 1/2 pathways and induced macrophages into M2-like polarization. The modulatory effects of vestitol are due to inhibition of NF-κB and Erk 1/2 signaling pathways, which are associated with the production of pro-inflammatory factors.

中文翻译：

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Vestitol 通过调节 NF-κB 通路驱动 LPS 激活的巨噬细胞进入 M2 表型


此前，我们在中性粒细胞模型中证明了马斯特醇的抗炎特性。在这里，我们展示了维斯特醇对巨噬细胞活化和功能的影响。 Vestitol 经过生物引导分级分离后从巴西红蜂胶中获得，并在 LPS 激活的 RAW 264.7 鼠巨噬细胞中测试不同浓度的一氧化氮 (NO) 产生和细胞活力。 TNF-α、IL1-β、TGF-β、IL-4、IL-6、IL-10、IL-12、GM-CSF、IFN-ɣ水平及细胞因子、NO、PI3K-AKT相关基因表达量分别通过ELISA和RT-qPCR检测信号转导通路。通过单向方差分析和 Tukey-Kramer 确定差异。与载体对照相比，0.55 μM Vestitol 可抑制 83% 的 NO 产生，且不影响细胞活力 (P < 0.05)。维斯托醇治疗可降低 GM-CSF、IL-6、TNF-α、IL-4 和 TGF-β 水平，并增加 IL-10 释放 (P < 0.05)。 Vestitol 影响与 NF-κB 通路、NO 合酶和白细胞迁移抑制相关的基因的表达，即：Ccs、Ccng1、Calm1、Tnfsf15、Il11、Gata3、Gadd45b、Cdkn1b、Csf1、Ccl5、Birc3（负调节）、 Vestitol 和 Igf1（正向调节）可减少 NF-κB 和 Erk 1/2 通路的激活，并诱导巨噬细胞进入 M2 样极化。 Vesitol 的调节作用是由于抑制 NF-κB 和 Erk 1/2 信号通路，这些信号通路与促炎因子的产生有关。