摘要
目的 通过体内外成分分析和网络药理学研究养阴生血合剂防治化疗并发症的潜在作用机制。方法 应用超高效液相色谱-四极杆-飞行时间质谱(UPLC-Q-TOF/MS)对养阴生血合剂的化学成分及其入血成分进行定性分析。从SwissTargetPrediction数据库获得入血成分对应的靶点,DrugBank,GeneCards和OMIM数据库获得化疗并发症相关靶点,并筛选养阴生血合剂和化疗并发症的交集靶点。利用STRING数据库获取蛋白相互作用(PPI)网络图,利用DAVID数据库对交集靶点进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析,使用Cytoscape软件绘制化学成分-靶点-通路网络,应用Auto Dock软件对主要活性成分和关键靶点进行分子对接验证。结果 灌胃给予养阴生血合剂后,自大鼠血清中鉴定出哈巴苷、黄芪甲苷、黄芪皂苷Ⅱ、毛蕊异黄酮、阿魏酸、毛蕊异黄酮苷、地黄苷D、毛蕊花糖苷和8-表番木鳖酸9种入血成分。筛选得到养阴生血合剂-化疗并发症交集靶点48个,包括EGFR,TNF,STAT3,IL-2等核心靶点15个,主要涉及核因子κB(NF-κB)和白介素-17(IL-17)等信号通路。分子对接结果显示,毛蕊异黄酮和黄芪甲苷与核心靶点EGFR和TNF的对接结合能均<-5 kJ/mol。结论 养阴生血合剂及其有效成分毛蕊异黄酮和黄芪甲苷可能通过作用于EGFR和TNF等靶点,调控NF-κB和IL-17等免疫炎症信号通路,从而发挥对化疗并发症的治疗作用。
Objective To study the potential mechanism of Yangyin Shengxue mixture in the prevention and treatment of chemo‐therapy complications based on the chemical component analysis in vitro and in vivo and network pharmacology.Methods The ultra performance liquid chromatography‐quadrupole‐time of flight mass spectrometry(UPLC‐Q‐TOF/MS)was used to qualitatively analyze the chemical components of Yangyin Shengxue mixture and the components absorbed in the blood.The targets related with Yangyin Shengxue mixture components absorbed in the blood were obtained from SwissTargetPrediction database,and the chemotherapy com‐plications‐related targets were obtained from DrugBank,GeneCards and OMIM databases.The intersection targets of Yangyin Shengxue mixture and chemotherapy complications were screened.The STRING database was used to construct PPI network,and DAVID database was employed for gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Cyto‐scape software was used to construct the chemical component‐target‐pathway network.The affinity of the key components and targets was predicted by Auto Dock software.Results After oral treatment with Yangyin Shengxue mixture,a total of 9 components from rats serum were identified,including harpagide,astragalosideⅣ,astragalosideⅡ,calycosin,ferulic acid,calycosin‐7‐O‐β‐D‐glucopyranoside,rehmannioside D,acteoside and 8‐epiloganic acid.Moreover,a total of 48 intersection targets and 15 core targets including EGFR,TNF,STAT3,IL‐2 and others were screened,mainly involving nuclear factor‐κB(NF‐κB)and interleukin‐17(IL‐17)signaling pathway and others.The molecular docking results exhibited that the binding energies of calycosin and astragalosideⅣwith the core targets of EGFR and TNF were all<-5 kJ/mol.Conclusion Yangyin Shengxue mixture and its active components,caly‐cosin and astragalosideⅣ,may play a role in the prevention and treatment of chemotherapy complications through regulating the targets o
作者
张萌萌
刘典焱
郭容利
李海洋
李瑶
宋建芳
丁茹
卫培峰
ZHANG Mengmeng;LIU Dianyan;GUO Rongli;LI Haiyang;LI Yao;SONG Jianfang;DING Ru;WEI Peifeng(Department of Traditional Chinese Medicine,School of pharmacy,Shaanxi University of Chinese Medicine,Xianyang 712046,China;Department of Research and Development,Shaanxi Jianmin Pharmaceutical Co.,Ltd)
出处
《山西医科大学学报》
CAS
2024年第10期1324-1334,共11页
Journal of Shanxi Medical University
基金
秦创原引用高层次创新创业人才项目(QCYRCXM-2023-109)。
