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.

以前，我们在嗜中性粒细胞模型中证明了vestitol的抗炎特性。在这里，我们显示了vestitol对巨噬细胞激活和功能的影响。在生物引导分级分离后，从巴西红蜂胶中获得了雌二醇，并在LPS活化的RAW 264.7鼠巨噬细胞中以不同浓度测试了一氧化氮（NO）的产生和细胞活力。TNF-α，IL1-β，TGF-β，IL-4，IL-6，IL-10，IL-12，GM-CSF，IFN-γ的水平以及与细胞因子，NO，PI3K-AKT相关的基因表达信号转导途径分别通过ELISA和RT-qPCR进行测定。差异是通过单向方差分析，然后是Tukey-Kramer确定的。与媒介物对照相比，雌二醇在0.55μM时可抑制NO生成83％，而不会影响细胞生存力（P <0.05）。用马甲糖醇治疗可降低GM-CSF，IL-6，TNF-α，IL-4和TGF-β的水平并增加IL-10的释放（P  <0.05）。雌二醇影响与NF-κB通路，NO合酶相关的基因的表达，并抑制白细胞迁移，包括：Ccs，Ccng1，Calm1，Tnfsf15，Il11，Gata3，Gadd45b，Cdkn1b，Csf1，Ccl5，Birc3（负调控），和Igf1（积极调节）。雌二醇减少了NF-κB和Erk 1/2途径的激活，并诱导巨噬细胞进入M2样极化。甾醇的调节作用归因于NF-κB和Erk 1/2信号通路的抑制，这与促炎因子的产生有关。