摘要
通过血清药物化学和网络药理学方法探讨金贝口服液(Jinbei Oral Liquid,JBOL)抗特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)的药效物质基础。基于超高效液相色谱-四极杆飞行时间串联质谱(UHPLC-Q-TOF-MS/MS)技术对大鼠口服JBOL后的入血成分进行分析鉴定,结合网络药理学通过蛋白-蛋白互作(PPI)网络构建及“成分-靶点-通路”、基因本体论(GO)功能富集和京都基因与基因组百科全书(KEGG)通路富集分析,探究了JBOL抗特发性肺纤维化的药效物质基础和潜在作用机制。首先,根据化合物的精确相对分子质量、碎片离子等信息结合对照品以及自建化合物库在JBOL提取物中快速鉴定出114种化合物。其次,在此基础上,通过对比空白血清与含药血清样品识别到70种入血原型成分,包括黄酮类28种、有机酸类25种、皂苷类和生物碱类各4种、其他类9种。最后,以入血成分为候选化合物,获得JBOL抗特发性肺纤维化的潜在靶点212个,推测其作用机制可能是通过甘草次酸、隐丹参酮、丹酚酸B、连翘酯苷A等活性成分作用于AKT1、TNF、ALB等核心靶点,调节PI3K/AKT、HIF-1、TNF等多种信号通路,发挥抗特发性肺纤维化作用。综上,JBOL可能通过多成分、多靶点、多通路发挥抗肺纤维化作用,研究结果为深入探讨其药效物质基础及药理机制提供了参考。
This study aims to explore the pharmacodynamic material basis of Jinbei Oral Liquid(JBOL)against idiopathic pulmonary fibrosis(IPF)based on serum pharmacochemistry and network pharmacology.The ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS)technology was employed to analyze and identify the components absorbed into rat blood after oral administration of JBOL.Combined with network pharmacology,the study explored the pharmacodynamic material basis and potential mechanism of JBOL against IPF through protein-protein interaction(PPI)network construction,"component-target-pathway"analysis,Gene Ontology(GO)functional enrichment,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.First,a total of 114 compounds were rapidly identified in JBOL extract according to the exact relative molecular mass,fragment ions,and other information of the compounds with the use of reference substances and a self-built compound database.Second,on this basis,70 prototype components in blood were recognized by comparing blank serum with drug-containing serum samples,including 28 flavonoids,25 organic acids,4 saponins,4 alkaloids,and 9 others.Finally,using these components absorbed into blood as candidates,the study obtained 212 potential targets of JBOL against IPF.The anti-IPF mechanism might involve the action of active ingredients such as glycyrrhetinic acid,cryptotanshinone,salvianolic acid B,and forsythoside A on core targets like AKT1,TNF,and ALB and thereby the regulation of multiple signaling pathways including PI3K/AKT,HIF-1,and TNF.In conclusion,JBOL exerts the anti-IPF effect through multiple components,targets,and pathways.The results would provide a reference for further study on pharmacodynamic material basis and pharmacological mechanism of JBOL.
作者
雷金春
张思彤
胡先润
刘文康
程雪梅
吴晓俊
陈万生
李曼琳
王长虹
LEI Jin-chun;ZHANG Si-tong;HU Xian-run;LIU Wen-kang;CHENG Xue-mei;WU Xiao-jun;CHEN Wan-sheng;LI Man-lin;WANG Chang-hong(Key Laboratory of Standardization of Chinese Materia Medica,Ministry of Education,Shanghai Key Laboratory of Compound Chinese Medicines,Institute of Chinese Materia Medica,Shanghai University of Traditional Chinese Medicine,Shanghai201203,China)
出处
《中国中药杂志》
北大核心
2025年第10期2825-2840,共16页
China Journal of Chinese Materia Medica
基金
国家重点研发计划项目(2022YFC3501701)。
作者简介
通信作者:李曼琳,博士,助理研究员,主要从事中药药效物质基础与药物代谢动力学研究,Tel:(021)51322504,E-mail:manlinli_cn@163.com;通信作者:王长虹,博士,研究员,博士生导师,主要从事药新制剂与体内过程研究,Tel:(021)51322511,E-mail:wchcxm@163.com;雷金春,硕士研究生,E-mail:L66887573@163.com。
