5, 7, 2′, 4′, 5′-Pentamethoxyflavanone regulates M1/M2 macrophage phenotype and protects the septic mice
5, 7, 2′, 4′, 5′-Pentamethoxyflavanone regulates M1/M2 macrophage phenotype and protects the septic mice
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DOI：
10.1016/s1875-5364(19)30042-1
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发表时间：
2019-05-20
影响因子：
4.6
通讯作者：
Xu Qiang
中科院分区：
文献类型：
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作者：
Feng Li-Li;Xu Li-Sha;Xu Qiang
据报道，黄酮类化合物对多种炎症性疾病具有保护作用，但其潜在的细胞机制仍未完全明晰。在本研究中，我们通过体外和体内实验，探究了一种多甲氧基黄酮类化合物——5,7,2',4',5'-五甲氧基黄烷酮（简称为Pen.）的抗炎活性。即便在高剂量处理下，Pen.对巨噬细胞也无明显毒性。我们的研究结果表明，Pen.能显著抑制促炎细胞因子白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）以及诱导型一氧化氮合酶（iNOS）的mRNA和蛋白质水平，这些均为M1极化巨噬细胞的特征性表达。Pen.的这些作用通过M1巨噬细胞表面标志物CD11c表达的降低得到进一步证实。进一步研究显示，其作用机制在于Pen.下调了M1极化关键转录因子p65的活性。另一方面，Pen.还通过上调抗炎因子以及增加M2巨噬细胞表面标志物来促进M2极化，从而促使M1和M2巨噬细胞达到平衡。此外，体内研究证实，Pen.处理可提高小鼠存活率、降低炎症细胞因子水平并改善肺组织损伤，进而缓解脂多糖（LPS）诱导的小鼠败血症。总之，我们的研究结果表明，Pen.通过抑制p65信号通路来调节巨噬细胞表型，从而发挥抗炎活性。
Flavonoids have been reported to exert protective effect against many inflammatory diseases, while the underlying cellular mechanisms are still not completely known. In the present study, we explored the anti-inflammation activity of 5, 7, 2', 4', 5'-pentamethoxyflavanone (abbreviated as Pen.), a kind of polymethoxylated flavonoid, both in vitro and in vivo experiments. Pen. was showed no obvious toxicity in macrophages even at high dosage treatment. Our results indicated that Pen. significantly inhibited both mRNA and protein level of proinflammatory cytokines, IL-1 beta, IL-6, TNF-alpha and iNOS, which was characteristic expressed on Ml polarized macrophages. These effects of Pen. were further confirmed by diminished expression of CD11c, the M1 macrophage surface marker. Further researches showed that the mechanism was due to that Pen. downregulated the activity of p65, key transcription factor for M1 polarization. On the other hand, Pen. also enhanced M2 polarization with upregulation of anti-inflammatory factors and increase of M2 macrophage surface markers, which lead to the balance of M1 and M2 macrophages. Moreover, in vivo research verified that Pen. treatment alleviated LPS-induced sepsis in mice by increasing survival rate, decreasing inflammatory cytokines and improving lung tissue damage. In summary, our results suggested that Pen. modulated macrophage phenotype via suppressing p65 signal pathway to exert the anti-inflammation activity.