基于网络药理学葛根解热作用机制研究

Network pharmacology-based study on mechanisms of antipyretic action of Pueraria radix

采用活性成分筛选、靶点预测技术,确定葛根解热作用有效成分及作用靶点,生物信息学技术富集通路及生物过程,分子对接验证网络分析结果,阐述葛根解热作用的作用机制。结果显示,葛根49个有效成分可能调控PTGS2和EGFR等21个靶点,显著影响环氧化酶通路、前列腺素合成、正向调节发热、炎症反应等11条生物过程及花生四烯酸代谢、5羟色胺突触、HIF-1信号等7条代谢通路。分子对接验证显示, 65%以上的有效成分与关键靶点具有结合活性,相关文献也显示结果所得活性成分能够抑制关键靶点PTGS2表达,说明结果可靠性较高。研究结果表明,葛根可能通过"多成分、多靶点和多通路"作用发挥解热作用,为葛根的进一步研究及其产品开发提供了科学依据。

This study was designed to explore the antipyretic mechanism of Pueraria radix. The method of network pharmacology was used to determine the known ingredients corresponding to Pueraria radix, predict the drug-related gene/protein targets, and analyze the interplay between key ingredients and targets. Biological Infor‐mation Annotation Databases(DAVID) was used to enrich the biological processes and pathways. The result of network analysis was validated by molecular docking. It was found that 49 active ingredients of Pueraria radix not only regulate 21 targets(e. g. PTGS2, EGFR), but also affect 11 biological processes(e. g. oxidation-reduction process, prostaglandin synthesis, positive regulation of fever generation and inflammatory response) and 7 metabolic pathways(arachidonic acid metabolism, serotonergic synapse and HIF-1, et al). Molecular docking results showed that more than 65% of the active ingredients could be well docked with key targets, and the relevant literatures indicated that the active components could inhibit the expression of PTGS2, which means the result has a high reliability. These results indicated that Pueraria radix may carry its pyretic action via a "multi-ingredients-multitargets-multi-pathways" mode, which provides a scientific basis for further research and drug development.