[关键词]
[摘要]
目的 采用超高效液相色谱-串联质谱(UPLC-MS/MS)法结合网络药理学研究肺筋草防治急性肺损伤(ALI)的入血成分及药效作用。方法 采用UPLC-MS/MS对肺筋草入血成分进行鉴定,结合网络药理学和分子对接探究肺筋草预防ALI的药效物质基础,最后通过体外实验验证肺筋草总酮对于炎症反应的抑制作用。结果 在肺筋草防治ALI有效作用下,共得到71个入血原型成分。根据变量重要性投影值(VIP)>1.4筛选指标性成分,共得到42个指标性成分。以指标性成分为候选化合物,获得肺筋草预防ALI的潜在靶点117个,推测其作用机制可能是通过芹菜素、2-氧-3,4-二氢-1H-喹啉-3-羧酸、3',4',7-三羟基酮等活性成分作用于SRC、STAT3、PTGS2、EGFR、ESR1等核心靶点,调节IL-17、c AMP、TNF、MAPK等多种信号通路。体外实验表明,与模型组相比,地塞米松组和肺筋草总酮组的炎症因子表达水平明显降低,说明肺筋草总酮对RAW264.7巨噬细胞的炎症反应具有一定的抑制作用。结论 初步阐明肺筋草预防ALI的药效物质基础,为其总酮治疗ALI的作用机制深入研究提供了参考。
[Key word]
[Abstract]
Objective To study the blood components and pharmacodynamic effects of Aletris spicataon acute lung injury(ALI) by using ultrahigh performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) combined with network pharmacology. Method UPLC-MS/MS was used to identify the blood components of A. spicata, and the pharmacological basis of A. spicata in preventing ALI was investigated by combining network pharmacology and molecular docking, and finally the inhibitory effect of total flavonoids of A. spicata on inflammation was verified by in vitro experiments. Result Under the effective action of A. spicata in preventing ALI, 71 prototype components were identified in the blood. Based on a VIP value > 1.4, 42 indicator components were screened. Using these indicator components as candidate compounds, 117 potential targets for the prevention of ALI by A. spicata were identified. The mechanism of action may involve active components such as apigenin, 2-oxo-3,4-dihydro-1H-quinoline-3-carboxylic acid and 3’,4’,7-trihydroxyflavone acting on core targets such as SRC, STAT3, PTGS2, EGFR, and ESR1, and regulating multiple signaling pathways including IL-17, cAMP, TNF, and MAPK. In vitro experiments showed that the expression levels of various inflammatory factors were significantly reduced in the positive group and the group administered with total flavonoids of A. spicata compared with the model group, suggesting that total flavonoids of A. spicata had a certain inhibitory effect on the inflammatory response of RAW264.macrophages. Conclusion This study preliminarily elucidated the pharmacodynamic material basis of A. spicata for the prevention of ALI, and provided a reference for the in-depth study of the mechanism of action of its total flavonoids in the treatment of ALI.
[中图分类号]
R285.5
[基金项目]
贵州省中医药管理局中医药、民族医药科学技术研究课题项目(QZYY-2022-015);贵州省科学技术基金项目(黔科合基础-ZK[2021]一般515)