Yupingfeng San Inhibits NLRP3 Inflammasome to Attenuate the Inflammatory Response in Asthma Mice.

Yupingfeng San Inhibits NLRP3 Inflammasome to Attenuate the Inflammatory Response in Asthma Mice.
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玉屏风散抑制NLRP3炎性体减轻哮喘小鼠炎症反应的研究

DOI:
10.3389/fphar.2017.00944
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发表时间:
2017
影响因子:
5.6
通讯作者:
He X
He X
中科院分区:
医学2区
文献类型:
--
作者:
Liu X;Shen J;Fan D;Qiu X;Guo Q;Zheng K;Luo H;Shu J;Lu C;Zhang G;Lu A;Ma C;He X

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玉屏风散是治疗支气管哮喘的代表性中药方剂。但其作用机制尚不清楚。本研究采用网络药理学的方法,探讨YPFS治疗哮喘的可能机制。核苷酸结合寡聚化结构域(NOD)样受体途径是与YPFS和哮喘相关的最常见的信号通路。此外,在YPFS调节哮喘的过程中,NOD样受体家族pyrin domain-containing 3(NLRP 3)炎性体作为靶蛋白。此外,通过使用LPS刺激的U937细胞和卵清蛋白(OVA)致敏的BALB/c小鼠模型进行实验验证。体外实验表明,YPFS可显着降低LPS刺激的U937细胞中TNF-α和IL-6的产生,以及IL-1β、NLRP 3、Caspase-1和ASC的mRNA和蛋白水平。体内实验表明,YPFS治疗不仅能减轻哮喘小鼠的临床症状,而且能减少哮喘小鼠肺组织中的炎性细胞浸润、粘液分泌和MUC 5AC的产生。YPFS能显著降低哮喘小鼠肺组织中IL-1β、NLRP 3、Caspase-1和ASC的mRNA和蛋白水平。总之,这些结果表明,YPFS可以抑制NLRP 3炎性体组分,以减轻哮喘的炎症反应。
Yupingfeng San (YPFS) is a representative Traditional Chinese Medicine (TCM) formula with accepted therapeutic effect on Asthma. However, its action mechanism is still obscure. In this study, we used network pharmacology to explore potential mechanism of YPFS on asthma. Nucleotide-binding oligomerization domain (NOD)-like receptor pathway was shown to be the top one shared signaling pathway associated with both YPFS and asthma. In addition, NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome was treated as target protein in the process of YPFS regulating asthma. Further, experimental validation was done by using LPS-stimulated U937 cells and ovalbumin (OVA)-sensitized BALB/c mice model. In vitro experiments showed that YPFS significantly decreased the production of TNF-α and IL-6, as well as both mRNA and protein levels of IL-1β, NLRP3, Caspase-1 and ASC in LPS-stimulated U937 cells. In vivo experiment indicated that YPFS treatment not only attenuated the clinical symptoms, but also reduced inflammatory cell infiltration, mucus secretion and MUC5AC production in lung tissue of asthmatic mice. Moreover, YPFS treatment remarkably decreased the mRNA and protein levels of IL-1β, NLRP3, Caspase-1 and ASC in lung tissue of asthmatic mice. In conclusion, these results demonstrated that YPFS could inhibit NLRP3 inflammasome components to attenuate the inflammatory response in asthma.
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