Beijing Key Lab for Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.
College of Life Sciences, Beijing University of Chinese Medicine, Beijing 102488, China.
J Pharm Biomed Anal. 2022 Jan 5;207:114396. doi: 10.1016/j.jpba.2021.114396. Epub 2021 Sep 28.
Euphorbia pekinensis Rupr. (EP) (Euphorbiaceae), as Traditional Chinese Medicine (TCM), exhibits therapeutic effects on tumors in clinical practice. Anti-angiogenesis may be an underlying molecular mechanism of EP's actions. However, the anti-angiogenic active ingredients of EP remain unclear. The screening and analysis of anti-angiogenic agents were essential for the sufficient utilization and development of EP. Thus, we established a UPLC-QTOF-MS method based on a transgenic zebrafish model to screen anti-angiogenesis activity components in EP. UPLC-QTOF-MS was used to characterize compounds from EP and in vivo compounds in Tg (flk1: mCherry) zebrafish larvae treated with EP. Based on the identification results, five components were selected, and their anti-angiogenesis activity were investigated via assessment of intersegmental blood vessels during the development of the transgenic zebrafish. Three of these components (3,3'-O-dimethoxy ellagic acid, quercetin, and ingenol) are active components of EP with anti-angiogenic effects. Among them, 3, 3'-O-dimethoxy ellagic acid and ingenol were first demonstrated with anti-angiogenesis effects. UPLC-PDA analysis was performed on EP water extracts to determine anti-angiogenesis active ingredients quantitatively. In the concentration range of 100-200 μg/mL, EP and the active ingredient compositions, mixed according to the content of EP, had equivalent anti-angiogenesis activities. These experimental results indicate that the UPLC-QTOF-MS method, combined with a transgenic zebrafish model, is rapid, sensitive and reliable. The combination in TCM offers the potential to achieve certain effect levels with lower concentrations of the individual compound.
京大戟（Euphorbia pekinensis Rupr.）（大戟科）作为一种传统中药，在临床实践中对肿瘤具有治疗作用。抗血管生成可能是其作用的潜在分子机制。然而，京大戟的抗血管生成活性成分仍不清楚。筛选和分析抗血管生成剂对于充分利用和开发京大戟至关重要。因此，我们建立了一种基于转基因斑马鱼模型的 UPLC-QTOF-MS 方法，以筛选京大戟中的抗血管生成活性成分。UPLC-QTOF-MS 用于表征京大戟中的化合物和用京大戟处理的 Tg（flk1: mCherry）斑马鱼幼虫中的体内化合物。基于鉴定结果，选择了五个成分，并通过评估转基因斑马鱼发育过程中的节间血管来研究它们的抗血管生成活性。其中三个成分（3,3'-O-二甲氧基鞣花酸、槲皮素和 ingenol）是具有抗血管生成作用的京大戟的活性成分。其中，3,3'-O-二甲氧基鞣花酸和 ingenol首次被证明具有抗血管生成作用。对京大戟水提取物进行 UPLC-PDA 分析，以定量测定抗血管生成活性成分。在 100-200μg/mL 的浓度范围内，京大戟及其按京大戟含量混合的活性成分组合物具有等效的抗血管生成活性。这些实验结果表明，UPLC-QTOF-MS 方法结合转基因斑马鱼模型快速、敏感、可靠。该组合为中药实现一定的效果水平提供了潜力，同时降低了单个化合物的浓度。
