天然产物研究与开发 ›› 2023, Vol. 35 ›› Issue (增刊1): 130-143.

• 数据研究 • 上一篇    下一篇

基于UPLC-LTQ-Orbitrap-MS/MS和网络药理学探讨消炎利胆片治疗胆管炎的药效物质和作用机制

车贵娟1,2,匡艳辉1,严曾豪1,王德勤1,张偲偲1*,刘晓秋2*   

  1. 1广州白云山和记黄埔中药有限公司,广州 510000;2沈阳药科大学,沈阳 110015
  • 出版日期:2023-06-28 发布日期:2023-06-13
  • 基金资助:
    名优中成药产学研深度融合发展服务平台(20212210006)

Pharmacodynamic substances and mechanism of Xiaoyan Lidan Pian in the treatment of cholangitis based on UPLC-LTQ-Orbitrap-MS/MS and network pharmacology

CHE Gui-juan1,2,KUANG Yan-hui1,YAN Zeng-hao1,WANG De-qin1,ZHANG Si-si1*,LIU Xiao-qiu2*   

  1. 1Guangzhou Baiyun Mountain Hutchison Whampoa Chinese Medicine Co.,Ltd.,Guangzhou 510000,China;2Shenyang Pharmaceutical University,Shenyang 110015,China
  • Online:2023-06-28 Published:2023-06-13

摘要:

基于超高效液相色谱-线性离子阱-静电场轨道阱高分辨质谱联用技术(UPLC-LTQ-Orbitrap-MS/MS)和网络药理学方法预测消炎利胆片(Xiaoyan Lidan Pian,XLP)治疗胆管炎的药效物质、潜在作用靶点和机制,为深入揭示其治疗胆管炎的作用机制奠定基础。通过UPLC-LTQ-Orbitrap-MS/MS检测XLP的化学成分,利用ThermoXcalibur软件在5×10-6的质量偏差范围内计算其精确分子式,结合文献中相关化合物裂解碎片信息及保留时间对化学成分进行定性分析。通过SwissADME数据库筛选成分;SwissTargetPrediction数据库预测成分作用靶点;OMIM、Drugbank、GeneCards数据库筛选治疗胆管炎相关的靶标。利用Metascape平台对潜在靶点进行GO功能富集和KEGG通路分析,Cytoscape 3.8.0软件构建“成分-靶点-通路”网络。从XLP中初步推断出89个化合物,主要包括生物碱类、黄酮类、内酯类、酚酸类、二萜类、三萜类等化合物;根据活性成分预测出876个潜在靶点,检索到疾病相关靶点461个,两者交集靶点76个,包括信号传导与转录激活因子3(STAT3)、白细胞介素-6(IL-6)、表皮生长因子受体(EGFR)等。涉及的通路有趋化因子信号通路、NF-κB信号通路、肿瘤坏死因子(TNF)信号通路、PI3K-Akt信号通路等。预测出XLP治疗胆管炎的药效物质有44个。其可能通过作用于STAT3、IL-6等靶点,调节多个信号通路发挥抗炎、减少胆汁淤积、抗肝纤维化的作用来治疗胆管炎。

关键词: 消炎利胆片, UPLC-LTQ-Orbitrap-MS/MS, 胆管炎, 网络药理学

Abstract:

Based on the ultra performance liquid chromatography-linear ion trap quadrupole-Orbitrap-mass spectrometry/mass spectrometry (UPLC-LTQ-Orbitrap-MS/MS) and network pharmacology,the pharmacodynamic substances,potential targets and mechanisms of Xiaoyan Lidan Pian (XLP) in the treatment of cholangitis were predicted,which laid a foundation for further revealing its mechanism of action in the treatment of cholangitis.Determination of chemical components of XLP by UPLC-LTQ-Orbitrap-MS/MS.Use ThermoXcalibur software to accurate calculate its precise molecular formula within the range of 5×10-6 mass deviation,and conduct qualitative analysis of chemical components in combination with the information of relevant compound fragmentation fragments and retention time in the literature.Using SwissADME database to filter components,SwissTargetPrediction database to predicted component tagets,OMIM,Drugbank and GeneCards database to collect disease targets;Cytoscape to construct an active ingredient-targets-pathway network.Eighty-nine compounds were preliminarily inferred from XLP,including alkaloids,flavonoids,lactones,phenolic acids,diterpenoids,triterpenoids.Eight hundred and seventy-six potential targets were predicted,four hundred and sixty-one disease-related targets were retrieved,and seventy-six intersection targets were identified,including signal transduction and transcription activator 3 (STAT3),interleukin-6 (IL-6),and epidermal growth factor receptor (EGFR),etc.The involved pathways include Chemokine signaling pathway,NF-κB signaling pathway,tumor necrosis factor (TNF) signaling pathway,PI3K-Akt signaling pathway,etc.The forecast results show 44 effective substances of XLP in treating cholangitis.It may act on STAT3,IL-6 and other targets,regulate multiple signal pathways to play the role of anti inflammation,reducing cholestasis and anti liver fibrosis to treat cholangitis.

Key words: Xiaoyan Lidan Pian, UPLC-LTQ-Orbitrap-MS/MS, cholangitis, network pharmacology

中图分类号:  R284