Wu-Mei-Wan Ameliorates Murine Ulcerative Colitis by Regulating Macrophage Polarization.

Wu-Mei-Wan Ameliorates Murine Ulcerative Colitis by Regulating Macrophage Polarization.
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乌梅丸通过调节巨噬细胞极化改善小鼠溃疡性结肠炎

DOI:
10.3389/fphar.2022.859167
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发表时间:
2022
影响因子:
5.6
通讯作者:
Li J
Li J
中科院分区:
医学2区
文献类型:
--
作者:
Yan S;Wei H;Jia R;Zhen M;Bao S;Wang W;Liu F;Li J

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越来越多的证据表明,巨噬细胞在溃疡性结肠炎(UC)的发病机制中起重要作用。据报道,巨噬细胞极化和相关信号通路的变化对肠道炎症具有保护作用。著名的中药乌梅丸(WMW)已被用于治疗腹泻,结肠炎的主要症状之一,超过2,000年。越来越多的证据表明,西洋参具有抑制肠道炎症和修复受损肠粘膜的作用,但其作用机制尚不清楚。因此,我们研究了WMW在葡聚糖硫酸钠(DSS)诱导的UC中的预防作用及其对巨噬细胞机制和极化的影响。结果显示,WMW组小鼠结肠炎明显减轻,血清和结肠组织中促炎因子TNF-α、IL-1和IL-6的分泌和表达受到抑制,而抗炎因子IL-10、Arg-1和TGF-β1则升高。随后的研究发现,WMW可以抑制DSS诱导的结肠炎小鼠结肠巨噬细胞的M1极化,促进M2极化。利用网络药理学预测潜在的作用靶点和途径,并进一步研究证实了相关作用靶点。结果表明,WMW可逐渐抑制P38 MAPK和NF-κB信号通路的激活,并进一步激活STAT 6信号通路。总之,WMW干扰p38 MAPK、NF-κB和STAT 6信号通路以调节巨噬细胞中的M1/M2极化,从而保护小鼠免受DSS诱导的结肠炎。
An increasing body of evidence shows that macrophages play an important role in the pathogenesis of ulcerative colitis (UC). Macrophage polarization and changes in related signaling pathways are reported to have a protective effect on intestinal inflammation. The well-known Chinese medicine Wumeiwan (WMW) has been used to treat diarrhea, one of the main symptoms of colitis, for more than 2,000 years. Increasing evidence shows that WMW can inhibit intestinal inflammation and repair damaged intestinal mucosa, but its effector mechanisms are unknown. Therefore, we studied the prophylactic effects of WMW in dextran sulfate sodium (DSS)-induced UC and its effects on macrophage mechanisms and polarization. The results show that colitis was significantly alleviated in mice in the WMW group, and the secretion and expression of pro-inflammatory factors TNF-α, IL-1, and IL-6 were inhibited in the serum and colonic tissues of mice with WMW-treated colitis, whereas anti-inflammatory factors IL-10, Arg-1, and TGF-β1 were increased. Subsequent studies found that WMW could inhibit M1 polarization and promote M2 polarization in colonic macrophages in DSS-induced colitis mice. Network pharmacology was used to predict potential targets and pathways, and further studies confirmed the related targets The results showed that WMW gradually inhibits the activation of the P38MAPK and NF-κB signaling pathways and further activates the STAT6 signaling pathway. In summary, WMW interferes with the p38MAPK, NF-κB and STAT6 signaling pathways to regulate M1/M2 polarization in macrophages, thereby protecting mice against DSS-induced colitis.
DOI: 10.1126/sciimmunol.aax6085
发表时间: 2020-05-22
期刊: Science immunology
影响因子: 24.8
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