基于网络药理学和分子对接探讨宁夏枸杞子中抑制免疫的成分及作用机制  

Discussion on the Composition and Mechanism of Lycium barbarum for Inhibiting Immune Based on Network Pharmacology and Molecular Docking

作　　者：许地元 乔亚玲 才让南加 林鹏程 海平 Xu Diyuan;Qiao Yaling;Cairang Nanjia;Lin Pengcheng;Hai Ping(College of Pharmacy,Qinghai Minzu University,Xining 810007,China;Qinghai Provincial Drug Inspection and Testing Institute/National Medical Products Administration Key Lab of Chinese and Tibetan Medicine Quality Control/Qinghai Key Lab of Chinese and Tibetan Medicine Modernization Study,Xining 810016,China;Key Laboratory of Phytochemistry in the Qinghai-Tibet Plateau,Xining 810007,China)

机构地区：[1]青海民族大学药学院,西宁810007 [2]青海省药品检验检测院/国家药品监督管理局中药(藏药)质量控制重点实验室/青海省中藏药现代化研究重点实验室,西宁810016 [3]青海省青藏高原植物化学重点实验室,西宁810007

出　　处：《青海科技》2023年第2期88-99,共12页Qinghai Science and Technology

基　　金：青海省科技计划项目(2020-SF-C32)。

摘　　要：通过网络药理学和分子对接技术,探究宁夏枸杞子乙酸乙酯萃取物中抑制程序性细胞死亡蛋白-1及其配体的活性成分及作用机制。通过检索文献和SwissTargetPrediction数据库,筛选出宁夏枸杞子乙酸乙酯萃取物中的成分及其对应靶点。在UniProt、OMIM、DrugBank和GeneCards数据库获取免疫相关靶点。采用Cytoscape软件构建化合物-关键免疫靶点-免疫通路网络图。运用String数据库构建蛋白质相互作用网络图(PPI)。利用DAVID数据库对关键免疫靶点进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。使用AutoDock Vina软件进行分子对接。宁夏枸杞子乙酸乙酯萃取物中活性成分共44种,活性成分与免疫交集靶点169个。PPI网络核心靶点有表皮生长因子受体(EGFR)、脾酪氨酸激酶(SYK)、雌激素受体(ESR1)等。GO富集显示活性成分可能通过蛋白磷酸化、肽基-酪氨酸自磷酸化、蛋白酪氨酸激酶活性等发挥抗免疫作用;KEGG通路显示活性成分可能通过FcεRI信号通路、B细胞受体信号通路、T细胞受体信号通路发挥作用;分子对接结果显示,化合物lyciumamide C、lyciumamide B与N-E-coumaroyl tyramine具有抑制PD-1/PD-L1的活性,核心蛋白与关键化合物之间的作用力主要是疏水相互作用、氢键和π-堆叠。宁夏枸杞子乙酸乙酯萃取物可通过多个靶点、多个通路发挥免疫抑制作用,lyciumamide C、lyciumamide B与N-E-coumaroyl tyramine是抑制PD-1/PD-L1的主要化合物。Objective To explore the composition and mechanism of Lycium barbarum for inhibiting PD-1/PD-L1 based on network pharmacology and molecular docking.Methods The active components of ethyl acetate layer of Lycium barbarum and their targets were screened by the literature and SwissTargetPrediction.The targets related to immune genes were obtained from UniProt、OMIM、DrugBank、GeneCards database.Cytoscape software was used to construct“components-key immune targets-immune pathway”network.String database was used to construct protein-protein interaction(PPI)network.GO and KEGG pathway enrichment of keyimmune targets were analyzed using DAVID database.AutoDock Vina was used for molecular docking。Results There were 44 active components in ethyl acetate layer of Lycium barbarum and 169 intersection targets of active and immunity.The core targets of PPI network were EGFR,SYK,ESR1,etc.GO enrichment analysis revealed that active ingredients may play an anti-immune role through protein phosphorylation,peptidyl-tyrosine autophosphorylation,protein tyrosine kinase activity,etc.KEGG pathway enrichment analysis revealed that active ingredients for regulate immunity was associated with FcεRI signaling pathway,B cell receptor signaling pathway,T cell receptor signaling pathway,etc.Molecular docking results showed that the compounds lyciumamide C,lyciumamide B and N-E-coumaroyl tyramine have the activity of inhibiting PD-1/PD-L1.The interactions between core proteins and key compounds are mainly hydrophobic interactions,hydrogen bonding andπ-stacking.Conclusion The ethyl acetate layer of Lycium barbarum can inhibite PD-1/PD-L1 by regulating multiple pathways and targets.Lyciumamide C,lyciumamide B and N-E-coumaroyl tyramine are the main immunosuppressive extracts.

关 键 词：宁夏枸杞子 PD-1 PD-L1 N-E-coumaroyl tyramine 网络药理学 分子对接 

分 类 号：R284.1[医药卫生—中药学]