Screening 5-lipoxygenase inhibitors from Choerospondias axillaris via a novel enzyme immobilization targeted fishing technology
Currently, coronary heart disease (CHD) is prevalent worldwide, with its harmful impact second only to that of malignant tumors. A growing number of studies have confirmed that Choerospondias axillaris can significantly improve the therapeutic effect of CHD treatment and reduce the incidence of adverse reactions. However, its bioactive components and pharmacological mechanisms remain unclear. Based on a targeted fishing strategy, this study synthesized magnetic nanomaterials immobilized with 5-lipoxygenase (5-LOX) for screening and identifying 5-LOX inhibitors from the crude extract of Choerospondias axillaris . A total of 21 active components were identified and analyzed using ultra-high performance liquid chromatography-Q-Exactive Orbitrap tandem mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS/MS). By comparing the screened active components with reported 5-LOX inhibitors, 9 novel 5-LOX inhibitors were discovered. Further molecular docking was performed on these 9 inhibitors, and the pharmacological activity of the selected ligands was verified using a 5-LOX inhibitor screening kit (fluorescence method).The compounds are ranked by activity from strongest to weakest: Lobetyolin (23.92 μM), Anhydroicaritin (29.55 μM), Narirutin(33.66 μM), Fisetin (47.28 μM) and Naringin(59.02 μM). This novel enzyme-immobilized targeted fishing technology is expected to efficiently and accurately screen bioactive components targeting different receptors from complex substrates.
危险品化学品经营许可证（带存储）