基于网络药理学与分子对接技术的保健食品白及五味子颗粒保胃护肝作用机制和功效成分含量测定研究

Study on gastric mucosa protection mechanism and content of functional component in Baji Wuweizi Granule based on network pharmacology and molecular docking

基于网络药理学和分子对接筛选辨识白及五味子颗粒中保胃护肝的功效成分及作用机制,并利用HPLC-DAD建立含量测定方法。该研究遵循多个功效成分共同测定取代总成分测定以提升保健食品质量控制总体思路,采用网络药理学的方法对功效成分进行筛选。基于TCMSP、GEO和Genecards等数据库共收集白及五味子颗粒的59个目标成分和74个疾病与成分的共同作用靶点,采用PPI平台及“成分-靶点-疾病”网络筛选得到包括AKT1、JUN等11个核心靶点与橙皮苷、芒柄花素、川陈皮素、五味子醇甲、五味子甲素和五味子乙素共6个功效成分。通过对共同作用靶点进行GO和KEGG富集分析可知,白及五味子颗粒保胃护肝功能的发挥涉及对化学应激的反应、类固醇代谢过程、对酒精的反应、脂质和动脉粥样硬化通路、IL-17信号通路等关于脂质代谢、氧化应激和炎症反应的通路。提示了白及五味子颗粒发挥保胃护肝功能是通过多成分、多靶点、多通路的协同作用实现的。对筛选得到的功效成分与核心靶点的结合能力进行预测分析,结果显示,所有成分均与核心靶点结合情况良好,结合活性综合排名前3位分别是橙皮苷、五味子醇甲与五味子甲素。此外,对功效成分建立含量测定方法完成对白及五味子颗粒中功效成分的含量测定。该研究结果为保健食品白及五味子颗粒中保胃护肝功效成分的发现和作用机制的阐明提供了思路,建立的功效成分含量测定方法准确、稳定,为实际生产中质量控制环节提供参考。

To screen and identify the quality markers from Baiji Wuweizi Granule with the function of the protection of liver injury and gastric mucosa injury based on the network pharmacology and molecular docking,an HPLC-DAD content determination method was established.This study obeyed the general idea of improving the quality control of healthy food by replacing the determination of total components with the determination of multiple functional components to enable the quality of the product and adopted the concept of quality markers in the quality control of traditional Chinese medicine to screen the functional components by the method of network pharmacology.59 main components of Baiji Wuweizi Granule and 74 same targets of diseases and herbs were collected from TCMSP,GEO,and Genecards databases.Functional components and core targets were obtained based on PPI and the“drug-disease-targets”network.Eleven core targets including AKT1,PTGS2,and HSP90AA1 were obtained,and six functional components,including hesperidin,schisandrin,nobiletin,schisandrin B,formononetin,and deoxyschizandrin,having the protection of gastric mucosa and liver injury were obtained.Results of the enrichment of GO and KEGG showed that the reaction to chemical stress,steroid metabolism,alcohol,lipid,and atherosclerosis pathway,IL-17 signalling pathway,and other pathways related to lipid metabolism,oxidative stress,and inflammatory response was involved in the function of Baiji Wuweizi Granule in protecting stomach and liver.Results indicated that the mode of“multi-component-multi-target-multi-pathway”was the implementation method of the Baiji Wuweizi Granule function.The ligand-receptor level binding activity of the target and components was predicted by the molecular docking method,while the results showed that all components could bind well with targets,and the top 3 binding activities were hesperidin,schisandrin,and deoxyschizandrin,respectively.In addition,the content determination results showed that all functional components could be detected in the product.The results of this study provided an idea for the discovery of quality markers in Baiji Wuweizi granules of healthy food,and the established method for the determination of quality markers was accurate and stable,which provided a reference for quality control in actual production.