加味香薷口服液抗流感的药效学及作用机制

Pharmacodynamic and Mechanism of Anti-influenza Effect of Jiawei Xiangru Oral Liquid

关键词:  加味香薷口服液  流感  网络药理学  药效学

Key words:  Jiawei Xiangru oral liquid  influenza  network pharmacology  pharmacodynamics

摘要:

目的 通过狗肾细胞(MDCK细胞)与小鼠观察加味香薷口服液的抗流感作用，并结合网络药理学预测其治疗流感的作用机制。方法 观察不同浓度加味香薷口服液对甲型流感病毒3型致MDCK细胞病变的影响，以及对流感病毒感染小鼠的保护作用。通过中药系统药理学数据库与分析平台(TCMSP)收集各味药的有效成分及作用靶点。采用GeneCards 5.14数据库、OMMI等数据库收集流感疾病相关靶点，构建网络图。借助STRING数据库及Metascape数据库构建PPI网络图、GO富集和KEGG通路分析。利用AutoDockTools和PyMOL软件完成分子对接及三维可视化展示。结果 体外实验表明加味香薷口服液对流感病毒引起的MDCK细胞病变及血凝现象有明显的抑制作用；体内实验表明其可延长甲型流感病毒感染小鼠存活时间，提高病毒感染小鼠的死亡保护率、降低小鼠肺指数及肺组织病毒滴度。筛选出82个活性成分和168个共有靶点，其中胡萝卜苷、叶酸、3`-甲氧基大豆黄素、柯伊利素、山柰酚为关键成分；TNF、AKT1、EGFR、STAT3、SRC、MMP9、PTGS2为核心靶点；KEGG通路富集分析显示其主要作用机制可能为通过TNF信号通路、趋化因子信号通路、PI3K/Akt信号通路、VEGF信号通路发挥抗流感病毒作用。结论 药效学结果表明加味香薷口服液可有效治疗流感疾病，其机制可能与“多成分-多靶点-多通路”协同调节有关。

Abstract:

OBJECTIVE To observe the anti-influenza effect of Jiawei Xiangru oral liquid through MDCK cells and mice, and predict its therapeutic mechanism for influenza based on network pharmacology. METHODS Observed the effect of different concentrations of Jiawei Xiangru oral liquid on MDCK cell damage caused by influenza A virus type 3 and its protective effect on influenza virus infected mice. The effective ingredients and action targets of each drug were collected through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). Collect influenza disease related targets using GeneCards 5.14, OMMI and other databases, and construct a network diagram. Build PPI network diagrams, GO enrichment, and KEGG pathway analysis using STRING and Metascape databases. Complete molecular docking and 3D visualization display using AutoDockTools and PyMOL software. RESULTS In vitro experiments shown that the Jiawei Xiangru oral liquid had a significant inhibitory effect on MDCK cell damage and hemagglutination caused by influenza virus. In vivo experiments shown that it could prolong the survival time of mice infected with influenza A virus, improve the death protection rate of mice infected with the virus, and reduce the lung index and lung tissue virus titer of mice. The 82 active ingredients and 168 common targets were screened, with carotenoid, folic acid, 3'- methoxy daidzein, coellitin, and kaempferol as key components, and TNF, AKT1, EGFR, STAT3, SRC, MMP9, and PTGS2 as core targets. KEGG pathway enrichment analysis showed that the main mechanism of action maight exert anti-influenza virus effects through the TNF signaling pathway, chemokine signaling pathway, PI3K/Akt signaling pathway, and VEGF signaling pathway. CONCLUSION Pharmacodynamics have shown that the Jiawei Xiangru oral liquid can effectively treat influenza diseases, and its mechanism maybe related to the synergistic regulation of "multi components, multi targets, and multi pathways".