Ganghuo Kanggan Decoction in Influenza: Integrating Network Pharmacology and In Vivo Pharmacological Evaluation.
Ganghuo Kanggan Decoction in Influenza: Integrating Network Pharmacology and In Vivo Pharmacological Evaluation.
复制标题
DOI：
10.3389/fphar.2020.607027
复制
发表时间：
2020
影响因子：
5.6
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Lai Y;Zhang Q;Long H;Han T;Li G;Zhan S;Li Y;Li Z;Jiang Y;Liu X
背景资料：港火抗感汤是我国岭南地区治疗病毒性肺炎的临床经验方，临床疗效显著。然而，GHKGD在流感中的作用机制尚不清楚。 目的：预测GHKGD的活性成分和信号通路，探讨其治疗流感的作用机制，并利用网络药理学进行体内验证。 研究方法：通过化合物筛选、靶点预测和途径富集分析等一系列网络药理学策略，推测GHKGD治疗流感的潜在活性成分和治疗靶点。基于靶点网络和富集结果，建立甲型流感病毒（IAV）感染小鼠模型，评价GHKGD对流感的治疗作用，验证网络药理学预测的可能分子机制。 结果：共鉴定出116个候选活性化合物和17个潜在作用靶点。潜在靶点富集分析的结果表明，GHKGD可能涉及RLR信号通路来减少肺部炎症。体内实验表明，GHKGD对IAV感染小鼠引起的肺炎具有保护作用。与模型组相比，GHKGD组小鼠体重减轻减轻，肺组织炎性病变减轻（p < 0.05）。肺组织NP蛋白表达和病毒滴度均显著降低（p < 0.05）。GHKGD组RIG-I、NF-kB、STAT 1蛋白表达及MAVS、IRF 3/7 mRNA水平明显降低（p < 0.05）。经GHKGD治疗后，Th 1型细胞因子（IFN-γ、TNF-α、IL-2）水平升高，Th 2型细胞因子（IL-5、IL-4）表达降低（p < 0.05）。 结论：通过网络药理学策略和体内实验，揭示了GHKGD治疗流感的多靶点、多组分药理学特征，证实了其在抗流感过程中对RLR信号通路的调控作用。本研究为GHKGD新药的研发提供了理论依据。
Background: Ganghuo Kanggan decoction (GHKGD) is a clinical experience prescription used for the treatment of viral pneumonia in the Lingnan area of China, and its clinical effect is remarkable. However, the mechanism of GHKGD in influenza is still unclear. Objective: To predict the active components and signaling pathway of GHKGD and to explore its therapeutic mechanism in influenza and to verified it in vivo using network pharmacology. Methods: The potential active components and therapeutic targets of GHKGD in the treatment of influenza were hypothesized through a series of network pharmacological strategies, including compound screening, target prediction and pathway enrichment analysis. Based on the target network and enrichment results, a mouse model of influenza A virus (IAV) infection was established to evaluate the therapeutic effect of GHKGD on influenza and to verify the possible molecular mechanism predicted by network pharmacology. Results: A total of 116 candidate active compounds and 17 potential targets were identified. The results of the potential target enrichment analysis suggested GHKGD may involve the RLR signaling pathway to reduce inflammation in the lungs. In vivo experiments showed that GHKGD had a protective effect on pneumonia caused by IAV-infected mice. Compared with the untreated group, the weight loss in the GHKGD group in the BALB/c mice decreased, and the inflammatory pathological changes in lung tissue were reduced (p < 0.05). The expression of NP protein and the virus titers in lung were significantly decreased (p < 0.05). The protein expression of RIG-I, NF-kB, and STAT1 and the level of MAVS and IRF3/7 mRNA were remarkably inhibited in GHKGD group (p < 0.05). After the treatment with GHKGD, the level of Th1 cytokines (IFN-γ, TNF-α, IL-2) was increased, while the expression of Th2 (IL-5, IL4) cytokines was reduced (p < 0.05). Conclusion: Through a network pharmacology strategy and in vivo experiments, the multi-target and multi-component pharmacological characteristics of GHKGD in the treatment of influenza were revealed, and regulation of the RLR signaling pathway during the anti-influenza process was confirmed. This study provides a theoretical basis for the research and development of new drugs from GHKGD.
登录
查看更多内容
宿主对甲型流感病毒感染的免疫反应
影响因子：
7.3
作者：
Chen X;Liu S;Goraya MU;Maarouf M;Huang S;Chen JL
通讯作者：
Chen JL
DOI：
10.1038/nri3665
发表时间：
2014-05
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
BATMAN-TCM：中药分子机制生物信息学分析工具
影响因子：
4.6
作者：
Liu Z;Guo F;Wang Y;Li C;Zhang X;Li H;Diao L;Gu J;Wang W;Li D;He F
通讯作者：
He F
影响因子：
24.3
作者：
Herold, Susanne;Becker, Christin;Budinger, G. R. Scott
通讯作者：
Budinger, G. R. Scott
DOI：
10.1007/s00103-016-2324-9
发表时间：
2016-04-01
影响因子：
1.7
作者：
Buchholz, Udo;Buda, Silke;Uphoff, Helmut
通讯作者：
Uphoff, Helmut