Quaternity method for integrated screening, separation, extraction optimization, and bioactivity evaluation of acetylcholinesterase inhibitors from Sophora flavescens Aiton.

IF 3 3区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Phytochemical Analysis Pub Date : 2024-07-03 DOI:10.1002/pca.3415

Yutong Zhang, Yuchi Zhang, Sainan Li, Chunming Liu, Jiaqi Liang, Yuyu Nong, Ming Chen, Ruijun Sun

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引用次数: 0

Abstract

Introduction: Sophora flavescens Aiton (Fabaceae), a ubiquitous plant species in Asia, contains a wide range of pharmacologically active compounds, such as flavonoids, with potential anti-Alzheimer's disease (anti-AD) effects.

Objectives: The objective of the study is to develop a quaternity method for the screening, isolation, extraction optimization, and activity evaluation of acetylcholinesterase (AChE)-inhibiting compounds from S. flavescens to realize high-throughput screening of active substances in traditional Chinese medicine and to provide experimental data for the development of anti-AD drugs.

Methods: With AChE as the target molecule, affinity ultrafiltration and liquid chromatography-mass spectrometry were applied to screen for potential inhibitors of the enzyme in S. flavescens. Orthogonal array experiments combined with the multi-objective Non-Dominated Sorting Genetic Algorithm III was used for the first time to optimize the process for extracting the active substances. Enzyme inhibition kinetics and molecular docking studies were performed to verify the potential anti-AD effects of the active compounds.

Results: Five AChE-inhibiting compounds were identified: kushenol I, kurarinone, sophoraflavanone G, isokurarinone, and kushenol E. These were successfully separated at purities of 72.88%, 98.55%, 96.86%, 96.74%, and 95.84%, respectively, using the n-hexane/ethyl acetate/methanol/water (4.0/5.0/4.0/5.0, v/v/v/v), n-hexane/ethyl acetate/methanol/water (5.0/5.0/6.0/4.0, v/v/v/v), and n-hexane/ethyl acetate/methanol/water (4.9/5.1/5.7/4.3, v/v/v/v) mobile phase systems. Enzyme inhibition kinetics revealed that kushenol E had the best inhibitory effect.

Conclusion: This study elucidates the mechanism of action of five active AChE inhibitors in S. flavescens and provides a theoretical basis for the screening and development of anti-AD and other therapeutic drugs.

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从 Sophora flavescens Aiton 中综合筛选、分离、优化提取和评估乙酰胆碱酯酶抑制剂的四元方法。

简介Sophora flavescens Aiton（豆科）是一种在亚洲无处不在的植物物种，含有多种药理活性化合物，如黄酮类化合物，具有潜在的抗老年痴呆症（anti-Alzheimer's disease，anti-AD）作用：目的：本研究旨在开发一种四元化合物筛选、分离、提取优化和乙酰胆碱酯酶（AChE）抑制化合物活性评价的方法，以实现中药活性物质的高通量筛选，并为抗老年痴呆症药物的开发提供实验数据：方法：以乙酰胆碱酯酶（AChE）为目标分子，采用亲和超滤和液相色谱-质谱联用技术筛选出潜在的乙酰胆碱酯酶抑制剂。正交阵列实验结合多目标非支配排序遗传算法 III 首次用于优化提取活性物质的过程。通过酶抑制动力学和分子对接研究，验证了活性化合物潜在的抗逆转录酶作用：结果：共鉴定出 5 种 AChE 抑制化合物：苦参醇 I、苦参环酮、槐黄酮 G、异苦参环酮和苦参醇 E。在正己烷/乙酸乙酯/甲醇/水（4.0/5.0/4.0/5.0，v/v/v/v）、正己烷/乙酸乙酯/甲醇/水（5.0/5.0/6.0/4.0，v/v/v/v）和正己烷/乙酸乙酯/甲醇/水（4.9/5.1/5.7/4.3，v/v/v/v）流动相体系中，这些物质的分离纯度分别为 72.88%、98.55%、96.86%、96.74% 和 95.84%。酶抑制动力学显示，草酚 E 的抑制效果最好：本研究阐明了五种活性 AChE 抑制剂在 S. flavescens 中的作用机制，为筛选和开发抗厌氧菌酶和其他治疗药物提供了理论依据。

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来源期刊

Phytochemical Analysis 生物-分析化学

CiteScore

6.00

自引率

6.10%

发文量

审稿时长

1.7 months

期刊介绍： Phytochemical Analysis is devoted to the publication of original articles concerning the development, improvement, validation and/or extension of application of analytical methodology in the plant sciences. The spectrum of coverage is broad, encompassing methods and techniques relevant to the detection (including bio-screening), extraction, separation, purification, identification and quantification of compounds in plant biochemistry, plant cellular and molecular biology, plant biotechnology, the food sciences, agriculture and horticulture. The Journal publishes papers describing significant novelty in the analysis of whole plants (including algae), plant cells, tissues and organs, plant-derived extracts and plant products (including those which have been partially or completely refined for use in the food, agrochemical, pharmaceutical and related industries). All forms of physical, chemical, biochemical, spectroscopic, radiometric, electrometric, chromatographic, metabolomic and chemometric investigations of plant products (monomeric species as well as polymeric molecules such as nucleic acids, proteins, lipids and carbohydrates) are included within the remit of the Journal. Papers dealing with novel methods relating to areas such as data handling/ data mining in plant sciences will also be welcomed.