桂枝颗粒化学成分与增强免疫力分子机制研究  

Chemical Components and Molecule Mechanism to Improve the Immunity of Guizhi Granules

作　　者：孙元芳 王梦文 刘辉见 李莎莎 王希茜 严诗楷[1,2] 肖雪[1,4] Sun Yuanfang;Wang Mengwen;Liu Huijian;Li Shasha;Wang Xixi;Yan Shikai;Xiao Xue(Institute of Traditional Chinese Medicine,Guangdong Pharmaceutical University,Guangzhou 510006,China;School of Pharmacy,Shanghai Jiao Tong University,Shanghai,200240,China;The Second Clinical College of Guangzhou University of Chinese Medicine,Guangzhou 510006,China;Shanxi Taihang Pharmceutical Co.,Ltd,Changzhi 046000,China)

机构地区：[1]广东药科大学中医药研究所,广东广州510006 [2]上海交通大学药学院,上海200240 [3]广州中医药大学第二附属医院,广东广州510006 [4]山西太行药业股份有限公司,山西长治046000

出　　处：《实验与分析》2024年第4期62-71,共10页LABOR PRAXIS

基　　金：广东省中医药局中医药科研项目(科研平台专项)(20244046)。

摘　　要：本文对桂枝颗粒的化学成分进行分析,旨在揭示增强免疫力的可能活性成分及其潜在作用机制。基于HPLCESI-Q/TOFMS平台分析鉴定桂枝颗粒水提液中的化学成分,结合Swiss Target Prediction数据库预测桂枝颗粒中潜在活性成分的作用靶点。分别在在线人类孟德尔遗传数据库和Gene Cards数据库中以“immunity”为关键词查找靶点基因,合并去重后得到与免疫力相关靶点蛋白。将桂枝颗粒成分相关靶点与免疫力相关靶点的重合部分定义为桂枝颗粒增强免疫力的潜在作用靶点。运用String数据库获取蛋白相互作用关系网络,根据网络拓扑参数筛选核心靶点蛋白,并对其进行生物信息学分析。最后使用Autodock验证关键成分与靶点的相互作用。Cytoscape3.8.0软件被用于构建“药效成分-核心靶点”网络。本研究基于HPLC-ESI-Q/TOF MS共鉴定出桂枝颗粒水提液中的91个化学成分,其中香茅酸、光甘草宁、芍药苷、甘草查尔酮B、6-姜酚等56个成分可能是桂枝颗粒增强免疫力的关键活性成分。根据网络拓扑参数发现桂枝颗粒增强免疫力的核心靶点蛋白有AKT1、EGFR、ESR1、TNF、PTGS2、VEGFA、PPARG、HRAS、JUN、GAPDH、HSP90AA1。通路分析发现桂枝颗粒中药效成分主要通过调控雌激素、C型凝集素受体、丝裂原活化蛋白激酶、松弛素和血管内皮生长因子等信号通路来发挥增强免疫力的作用。最后分子对接结果显示桂枝颗粒中多个成分均可结合ESR1。本研究推定出桂枝颗粒中91个化学成分,通过网络药理学分析发现了桂枝颗粒增强免疫力的潜在药效成分和潜在机制,为其后续临床应用提供一定的理论基础。The aim of this study is to identify the components of Guizhi granules and explore its potential mechanism to improve the immunity of the body.Based on the HPLC-ESI-Q/TOF MS,the fingerprint of the aqueous extract of Guizhi granules was established,and the chemical components were identified.The targets protein of active components in Guizhi granules was predicted with the SwissTargetPrediction database.The immunity related genes were obtained from online mendelian inheritance in man and GeneCards databases.The overlapping part of Guizhi granule component related targets and immunity related targets was defined as the potential targets of Guizhi granule to improve immunity.The String database was used to obtain the protein interaction relationship network,screen the core target proteins,and carry out bioinformatics analysis.The network of“effective components-core targets”was built using Cytoscape 3.8.0 software.The molecular docking of compounds and key targets is achieved by autodock vina 1.1.2.The 91 chemical components in Guizhi granules were identified by HPLC-ESI-Q/TOF MS,and 56 components,such as citronella acid,glabranin,paeoniflorin,licochalcone B,6-gingerol,are the key effective ingredients of Guizhi granules to provide immunity.According to the network topology parameters,11 core target proteins were screened,including AKT1,EGFR,ESR1,TNF,PTGS2,VEGFA,PPARG,HRAS,JUN,GAPDH,HSP90AA1.The pathway analysis found that the effective components in Guizhi granules mainly play a role in improving immunity by regulating the signal pathways such as estrogen,C-type lectin receptor,mitogen activated protein kinase,relaxin and vascular endothelial growth factor.The results of molecular docking showed that multi-composition in Guizhi Granules had strong affinity with ESR1.This study identified 91 effective components in Guizhii granules,and elucidated the effective components and potential mechanisms of Guizhi granules to improve the immunity of the body,and provided a scientific theoretical basis for its subsequent

关 键 词：桂枝颗粒 药效成分 网络药理学 作用机制 

分 类 号：R917[医药卫生—药物分析学] R284.1[医药卫生—药学]