基于超高效液相色谱-质谱技术及网络药理学探究大血藤治疗脑梗死的有效成分及其潜在作用机制

Study on the effective ingredients and potential mechanism of Sargentodoxa cuneata in the treatment of cerebral infarction based on UPLC-HR-MS and network pharmacology

本文通过超高效液相色谱-串联高分辨质谱技术、网络药理学及分子对接技术探讨大血藤化学成分治疗脑梗死的潜在药效物质和作用机制。采用超高效液相色谱-高分辨质谱技术对大血藤化学成分进行初步分析,鉴定得到大血藤中化学成分共20个,包括苯丙素类、蒽醌类、酚酸类和三萜类等。在化学成分分析基础上,通过网络药理学方法建立可视化的“化学成分-疾病靶标-生物通路”网络,筛选其治疗脑梗死的潜在核心靶点共71个,包括PIK3CA、SRC和STAT3等。KEGG通路富集结果表明,大血藤可通过调控HIF-1信号通路、sphingolipid信号通路、ErbB信号通路等多条信号通路发挥作用。我们进一步对核心靶点进行分子对接验证,结果显示大血藤化学成分3,4-二羟基苯乙醇葡萄糖苷、紫罗兰酮苷、大黄素甲醚等与APP、PIK3CA、STAT3等靶点均具有良好的亲和性。本研究揭示了大血藤通过多成分、多靶点、多通路的调控发挥治疗脑梗死的潜在作用机制,为未来深入阐释大血藤治疗脑梗死的药效物质基础和作用机制提供有利线索及参考依据。

This study aims to predict the potential targets and molecular mechanism of Sargentodoxa cuneata for the treatment of cerebral infarction(CI)based on ultra-performance liquid chromatography-high-resolution mass spectrometry(UPLC-HR-MS),network pharmacology and molecular docking.UPLC-HR-MS was used to conduct a preliminary analysis of the chemical composition of S.cuneata.A total of 20 chemical constituents,including phenylpropanoids,anthraquinones,phenolic acids and triterpenoids were identified in S.cuneata.Based on chemical composition analysis,visual“chemical composition-disease target-biological pathway”network was established through network pharmacology analysis,and a total of 71 potential core targets for the treatment of CI were selected,including PIK3CA,SRC,STAT3 and so on.The enrichment results of the KEGG pathway suggested that the pathway of these key targets is mainly related to HIF-1,ErBb,sphingolipid pathways and so on.The molecular docking of the core targets was further verified,and the results showed that 3,4-dihydroxyphenylethyl alcohol glucoside,cuneataside E and physcion had good affinity with APP,PIK3CA,STAT3 and other targets.In summary,this paper indicates that the components of S.cuneata act on multiple targets,participate in the regulation of multiple pathways to exert the mechanism of treating CI,which provides a basis and reference for further verifying the pharmacodynamic substance and mechanism of S.cuneata for the treatment of CI.