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Rapid screening and isolation of 5‐lipoxygenase inhibitors in Inonotus obliquus and mechanism of action in the treatment of asthma
Journal of Separation Science ( IF 3.1 ) Pub Date : 2024-03-11 , DOI: 10.1002/jssc.202300647
Haocheng Yun 1 , Zhen Liu 1 , Wanchao Hou 1 , Qiang Liu 1 , Yuyu Nong 1 , Sainan Li 1 , Chunming Liu 1
Affiliation  

Accurate screening and targeted preparative isolation of active substances in natural medicines have long been two technical challenges in natural medicine research. This study outlines a new approach to improve the efficiency of natural product preparation, focusing on rapidly and accurately screening potential active ingredients in Inonotus obliquus as well as efficiently preparing 5‐lipoxidase (5‐LOX) inhibitors, to provide new ideas for the treatment of asthma with Inonotus obliquus. First, we used ultrafiltration (UF) mass spectrometry to screen for three potential inhibitors of 5‐LOX in Inonotus obliquus. Subsequently, the inhibitory effect of the active ingredients screened in the UF assay on 5‐LOX was verified using the molecular docking technique, and the potential role of the active compounds in Inonotus obliquus for the treatment of asthma was analyzed by network pharmacology. Finally, based on the above activity screening guidelines, we used semi‐preparative liquid chromatography and consecutive high‐speed countercurrent chromatography to isolate three high‐purity 5‐LOX inhibitors such as betulin, lanosterol, and quercetin. Obviously, through the above approach, we have seamlessly combined rapid discovery, screening, and centralized preparation of the active ingredient with molecular‐level interactions between the active ingredient and the protease.

中文翻译:

桦褐孔菌5-脂氧合酶抑制剂的快速筛选分离及其治疗哮喘的作用机制

天然药物活性物质的精准筛选和针对性制备分离一直是天然药物研究的两大技术挑战。该研究概述了一种提高天然产物制备效率的新方法,重点是快速、准确地筛选天然产物中的潜在活性成分。桦褐孔菌以及高效制备5-脂氧化酶(5-LOX)抑制剂,为哮喘的治疗提供新思路桦褐孔菌。首先,我们使用超滤(UF)质谱法筛选了三种潜在的 5-LOX 抑制剂。桦褐孔菌。随后,利用分子对接技术验证了超滤法筛选出的活性成分对5-LOX的抑制作用,以及活性化合物在抑制5-LOX中的潜在作用。桦褐孔菌通过网络药理学分析其治疗哮喘的效果。最后,根据上述活性筛选指南,我们使用半制备液相色谱和连续高速逆流色谱分离了桦木醇、羊毛甾醇和槲皮素等三种高纯度5-LOX抑制剂。显然,通过上述方法,我们将活性成分的快速发现、筛选和集中制备与活性成分与蛋白酶之间的分子水平相互作用无缝结合起来。
更新日期:2024-03-11
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