Network pharmacology-based study to investigate the mechanism of compound houttuynia mixture against influenza virus infection by suppressing TLR7/MyD88 signaling pathway

IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE
Hailin Wei , Wenlei Wang , Qin Su , Zhihui Zheng , Zihan Chen , Xinyue Zhang , Yihan Xu , Xiaoquan Wang , Pinghu Zhang
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Abstract

Aim of the study

Compound houttuynia mixture (CHM) has been approved to cure respiratory diseases in China. However, the anti-influenza virus effect and underlying mechanism of CHM remains to be confirmed.

Materials and methods

The in vitro activity of CHM against H3N2 virus was evaluated using MDCK, A549 and THP-1 cells as an in vitro model. The in vivo protective effect on H3N2 virus infection was investigated. Moreover, serum cytokines were measured with high throughput liquid phase protein chip. The anti-influenza mechanism of CHM was predicted by network pharmacology and further validated with immunoblotting.

Results

Our results indicated that CHM has significant inhibitory effect on the replication of influenza A H3N2 virus. Furthermore, CHM could effectively reduce the mortality caused by lethal H3N2 virus infection by prolonging the survival time, reducing lung pathological injury, and suppressing excessive cytokines storm. Network pharmacology revealed that the protective effect of CHM on influenza virus infection was involved in multiple targets and multiple pathways. Mechanistic validation indicated that inhibiting the excessive activation of TLR7/MyD88 signaling pathway may be the critical mechanism of CHM exerting the protective effect against influenza virus infection.

Conclusion

Regulating of TLR7/MyD88/NF-κB signaling pathway in multiple target cells might be one of key mechanisms of CHM by inhibiting virus replication and excessive inflammatory. Our findings indicated that CHM might be an effective treatment for influenza virus infection.

Abstract Image

基于网络药理学的研究,探讨复方鱼腥草混合物通过抑制 TLR7/MyD88 信号通路抗流感病毒感染的机制
研究目的:复方鱼腥草合剂(CHM)在中国已被批准用于治疗呼吸系统疾病。然而,中草药的抗流感病毒作用及其机制仍有待证实。材料与方法以MDCK、A549和THP-1细胞为体外模型,评价中药对H3N2病毒的体外活性。研究了其在体内对H3N2病毒感染的保护作用。采用高通量液相蛋白芯片检测血清细胞因子。用网络药理学方法预测中药抗流感的作用机制,并用免疫印迹法进一步验证。结果中药对甲型流感H3N2病毒的复制有明显的抑制作用。此外,CHM可通过延长存活时间、减轻肺病理损伤、抑制过量细胞因子风暴等方式,有效降低H3N2病毒致死性感染的死亡率。网络药理学研究表明,中草药对流感病毒感染的保护作用涉及多靶点、多途径。机制验证表明,抑制TLR7/MyD88信号通路的过度激活可能是中草药发挥流感病毒感染保护作用的关键机制。结论TLR7/MyD88/NF-κB信号通路在多靶细胞中的调控可能是抑制病毒复制和过度炎症的重要机制之一。我们的研究结果表明中草药可能是治疗流感病毒感染的有效方法。
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来源期刊
Journal of Traditional and Complementary Medicine
Journal of Traditional and Complementary Medicine Medicine-Complementary and Alternative Medicine
CiteScore
9.30
自引率
6.70%
发文量
78
审稿时长
66 days
期刊介绍: eJTCM is committed to publish research providing the biological and clinical grounds for using Traditional and Complementary Medical treatments as well as studies that demonstrate the pathophysiological and molecular/biochemical bases supporting the effectiveness of such treatments. Review articles are by invitation only. eJTCM is receiving an increasing amount of submission, and we need to adopt more stringent criteria to select the articles that can be considered for peer review. Note that eJTCM is striving to increase the quality and medical relevance of the publications.
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