基于网络药理学和分子对接技术分析少腹逐瘀汤治疗盆腔炎的作用机制及功效成分含量测定

Analysis of the mechanism of Shaofu Zhuyu Decoction in the treatment of pelvic inflammatory disease and determination of functional components based on network pharmacology and molecular docking technology

目的 基于网络药理学和分子对接技术分析少腹逐瘀汤治疗盆腔炎潜在的分子作用机制,并利用高效液相色谱-二极管阵列检测器(HPLC-DAD)建立功效物质基础含量的测定方法。方法 根据网络数据平台对少腹逐瘀汤的各味中药成分进行收集和筛选,获得了218种活性成分,得到了199个药物成分的靶点,建立“中药-药物成分-靶点”交互作用网络,筛选出关键功效物质基础。同时查找到2 558个盆腔炎相关的治疗靶点,取交集后得97个少腹逐瘀汤和盆腔炎的作用靶点,建立蛋白交互作用网络,筛选出70个核心蛋白,其中包括SRC、MAPK1和HSP90AA1。通过Metascape数据库对交集靶点进行富集分析。采用AutoDock Tools、Pymol等软件对以上过程所得结果进行分析和验证。此外,还对功效成分建立含量测定方法完成对少腹逐瘀汤中功效成分的含量测定。结果 少腹逐瘀汤与盆腔炎的共同生物学过程包括激素的响应、激酶活性的调节等;作用通路主要为癌症通路、脂质代谢与动脉粥样硬化通路、MAPK信号通路、PI3K-Akt信号通路等。分子对接的结果显示功效成分能与核心蛋白稳定的结合,并通过相关的残基进行对接,发生相互作用。结论 该研究为少腹逐瘀汤治疗盆腔炎的作用机制提供了思路,建立的功效成分含量测定方法准确、稳定,为临床应用中质量控制环节提供参考。

Objective To analyze the potential molecular mechanism of Shaofu Zhuyu Decoction(SZD)in the treatment of pelvic inflammatory disease based on network pharmacology and molecular docking technology,and establish a method for the determination of functional material by HPLC-DAD.Methods According to the network data platform,the traditional Chinese medicine components of SZD were collected and screened,218 active components were obtained,and the targets of 199 drug components were obtained.The″traditional Chinese medicine-drug component-target″interaction network was established to screen out the key functional material basis.At the same time,2558 therapeutic targets related to pelvic inflammatory disease were found,and 97 targets of SZD and pelvic inflammatory disease were obtained after intersection.The protein interaction network was established,and 70 core proteins were screened,including SRC,MAPK1 and HSP90AA1.Enrichment analysis of intersection targets was performed by Metascape database.The results obtained from the above process were analyzed and verified by AutoDock Tools,Pymol and other software.In addition,the content determination method of functional components was established to complete the content determination of functional components in SZD.Results The common biological processes of SZD and pelvic inflammatory disease include hormone response,regulation of kinase activity,etc.The main pathways are cancer pathway,lipid metabolism and atherosclerosis pathway,MAPK signaling pathway,PI3K-Akt signaling pathway and so on.The results of molecular docking showed that the functional components could bind to the core protein stably and interact with each other through the related residues.Conclusion This study provided ideas for the mechanism of SZD in the treatment of pelvic inflammatory disease.The established method for the determination of the content of functional components was accurate and stable,and provided a reference for quality control in clinical application.