Astragaloside IV Alleviates the Experimental DSS-Induced Colitis by Remodeling Macrophage Polarization Through STAT Signaling.

Astragaloside IV Alleviates the Experimental DSS-Induced Colitis by Remodeling Macrophage Polarization Through STAT Signaling.
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黄芪甲苷 IV 通过 STAT 信号传导重塑巨噬细胞极化,减轻实验性 DSS 诱发的结肠炎。

DOI:
10.3389/fimmu.2021.740565
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发表时间:
2021
影响因子:
7.3
通讯作者:
Lin Y
Lin Y
中科院分区:
医学2区
文献类型:
--
作者:
Tian L;Zhao JL;Kang JQ;Guo SB;Zhang N;Shang L;Zhang YL;Zhang J;Jiang X;Lin Y

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炎症性肠病(IBD)以慢性、复发性肠道炎症为特征,目前缺乏安全有效的药物。之前的一些研究表明,黄芪甲苷 IV (AS-IV) 是一种从中药川芎中提取的天然皂苷,可在体外和体内缓解实验性结肠炎症状。然而,AS-IV治疗IBD的机制仍不清楚。越来越多的证据表明,M2 极化肠道巨噬细胞在 IBD 进展中发挥着关键作用。在这里,我们发现 AS-IV 减弱了 DSS 诱导的模拟人类 IBD 的结肠炎的临床活性,并导致巨噬细胞从不成熟的促炎巨噬细胞向成熟的促消退巨噬细胞的表型转变。在体外,将骨髓源性巨噬细胞(BMDM)分别诱导为 M1/M2 并与 AS-IV 孵育后,通过 qRT-PCR 观察巨噬细胞的表型变化。此外,AS-IV 可通过调节 STAT 信号通路有效抑制促炎巨噬细胞并促进促消退巨噬细胞,从而改善实验性结肠炎。因此,我们认为 AS-IV 可以通过重塑 STAT 信号传导来调节巨噬细胞表型来部分改善实验性结肠炎,这似乎在 AS-IV 缓解 IBD 病理进展的能力中具有重要功能。
Inflammatory bowel disease (IBD) is characterized by chronic and relapsing intestinal inflammation, which currently lacks safe and effective medicine. Some previous studies indicated that Astragaloside IV (AS-IV), a natural saponin extracted from the traditional Chinese medicine herb Ligusticum chuanxiong, alleviates the experimental colitis symptoms in vitro and in vivo. However, the mechanism of AS-IV on IBD remains unclear. Accumulating evidence suggests that M2-polarized intestinal macrophages play a pivotal role in IBD progression. Here, we found that AS-IV attenuated clinical activity of DSS-induced colitis that mimics human IBD and resulted in the phenotypic transition of macrophages from immature pro-inflammatory macrophages to mature pro-resolving macrophages. In vitro, the phenotype changes of macrophages were observed by qRT-PCR after bone marrow-derived macrophages (BMDMs) were induced to M1/M2 and incubated with AS-IV, respectively. In addition, AS-IV was effective in inhibiting pro-inflammatory macrophages and promoting the pro-resolving macrophages to ameliorate experimental colitis via the regulation of the STAT signaling pathway. Hence, we propose that AS-IV can ameliorate experimental colitis partially by modulating macrophage phenotype by remodeling the STAT signaling, which seems to have an essential function in the ability of AS-IV to alleviate the pathological progress of IBD.
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