归肾经补阳药的网络药理学机制研究

Mechanism of Yang-tonifying herbs distributing along kidney meridians in molecular level by network pharmacology

目的运用网络药理学的方法对归肾经补阳药的分子作用机制进行预测。方法选择归肾经补阳中药肉苁蓉、菟丝子、冬虫夏草、韭菜子、沙苑子、仙茅、续断以及胡芦巴作为研究对象,通过TCMSP数据库检索中药化学成分,利用口服生物利用度(OB)、类药性(DL)值筛选活性成分及Pub Chem数据库的化学相似性靶点预测方法对中药活性成分进行靶点预测;通过STRING数据库寻找归肾经补阳药靶蛋白之间的相互作用关系以及KEGG通路分析;通过加权Page Rank算法评价蛋白互作(PPI)网络中的节点,并对信号通路进行打分。基于通路富集分析及PPI分析筛选核心靶蛋白。利用Cytoscape 3.6.0软件,分别构建化合物-关键靶点网络、药材-关键靶点PPI网络和关键靶点-通路网络,并对其作用机制进行了初步探讨。结果筛选出归肾经补阳药核心靶蛋白21个,信号通路40条。归肾经补阳中药可能通过T细胞调节、性激素调节、免疫反应、延缓衰老等途径发挥温补肾阳的作用,其作用机制可能与甲状腺激素、神经营养因子、TNF及雌激素等信号通路有关。结论基于网络药理学的研究方法有助于寻找归肾经补阳药的关键靶点和信号通路,为深入诠释补肾阳药的分类含义提供有益的信息和数据支撑。

Objective To predict the unique mechanism of Yang-tonifying herbs distributing along kidney meridians in molecular level through network pharmacology technology.Methods Eight kidney-yang tonifying herbs with common clinical effects and clear therapeutic effects were selected in study.The chemical ingredients of traditional Chinese medicines were searched by TCMSP database.OB and DL values were applied to screen the active substance and the chemical similarity target prediction methods of Pub Chem database were used to predict the target proteins of TCM;The PPI between the target proteins of the kidney-yang tonifying herbs and the KEGG signal pathway were searched by the STRING database;The nodes in the PPI network were evaluated by the weighted Page Rank algorithm and then the core target protein was screened.Using the Cytoscape 3.6.0 software,a compound-target network,a herb-target-PPI network,and a target-pathway network were constructed.Results Through the network analysis,21 key targets and 40 signal pathways of the kidney-yang tonifying herbs were screened.The medicinal played the role of warming and tonifying kidney-yang by T cell regulation,sex hormone regulation,immune response,and delaying aging.The mechanism may be related to thyroid hormone signaling pathway,neurotrophin signaling pathway,TNF signaling pathway and estrogen signaling pathway.Conclusion The method based on network pharmacology could help to find the key targets and signal pathways of the kidney-yang tonifying herbs,which provides useful information and data support for further interpretation of the classification meaning of the kidney-yang tonifying herbs in TCM.