GEO芯片分析联合网络药理学探讨五味子-枸杞子保护放射性肝损伤的机制研究

Protective effect of Schisandrae Chinensis Fructus and Lycii Fructus on radiation-induced liver injury based on GEO chip analysis and network pharmacology

利用转录组学、网络药理学和分子对接的技术预测五味子-枸杞子保护放射性肝损伤的活性成分、作用靶点及作用机制。通过中药系统药理学数据库与分析平台(TCMSP)筛选出五味子-枸杞子主要活性成分,从五味子中筛选出14个活性成分,枸杞子中筛选出25个活性成分,核心成分主要为槲皮素、黄豆黄素和去氧紫草素;通过GeneCards、在线人类孟德尔遗传数据库获得辐射损伤的靶点基因,利用UniProt对所获得的基因进行校正,共同关键靶点共66个,利用Cytoscape 3.8.0软件构建药物-活性成分-关键靶点-放射性肝损伤调控网络,将活性成分与疾病共同靶点上传至String数据库,构建药物靶蛋白-放射性肝损伤蛋白相互作用(PPI)网络,根据度值筛选关键核心靶点为CASP3、EGFR、ESR1;对关键靶点进行功能富集分析及通路富集分析,五味子-枸杞子活性成分主要参与化学致癌-受体激活、脂质与动脉粥样硬、PI3K-Akt、MAPK、凋亡等信号通路;分子对接结果提示3个活性成分与靶蛋白结合能力较强。本研究初步发现五味子-枸杞子可能通过槲皮素、黄豆黄素和去氧紫草素调节化学致癌-受体激活、脂质与动脉粥样硬、PI3K-Akt、MAPK、凋亡等多个信号通路发挥保护放射性肝损伤的作用。

Using transcriptomics,network pharmacology,and molecular docking techniques to predict the active components,targets,and mechanisms of Schisandrae Chinensis Fructus(SCF)and Lycii Fructus(LF)in protecting against radiation-induced liver injury.The main active components of SCF and LF were selected through traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP),14 active components were selected from SCF,and 25 active components were selected from LF.The core components were mainly quercetin,glycitein and arnebin 7;The target genes for radiation injury were obtained through genecards and online human mendelian genetic database,and the obtained genes were corrected by UniProt,a total of 66 key targets were found.A drug-active component-key target-radiation liver injury control network was constructed using cytascape software,and the targets for active components and diseases were uploaded to the string database,Construct a drug target protein radiation liver injury protein interaction network,and select the key core targets as CASP3,EGFR,and ESR1 based on the degree value;The function enrichment analysis and pathway enrichment analysis of key targets were carried out,The active components of SCF and LF were mainly involved in chemical carcinogenesis receptor activation,lipid and arterial atherosclerosis,PI3K-Akt,MAPK,apoptosis,etc;Molecular docking results suggest that the three active components have strong binding ability to target proteins.This study preliminarily found that SCF and LF may play a protective role in radiation-induced liver injury by regulating chemical carcinogenesis receptor activation,lipid and arterial atherosclerosis,PI3K-Akt,MAPK,apoptosis and other signaling pathways through quercetin,glycitein and arnebin 7.