Screening and identification of Euphorbiae pekinensis Rupr. anti-angiogenic multi-components with UPLC-QTOF-MS in zebrafish

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 antiangiogenic 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 mu g/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. (c) 2021 Elsevier B.V. All rights reserved.

Automated summary

This study successfully screened anti-angiogenic active components in Euphorbia pekinensis using UPLC-QTOF-MS method combined with a transgenic zebrafish model, with 3,3'-O-dimethoxy ellagic acid, quercetin, and ingenol showing significant anti-angiogenic effects.