基于磁珠的配体捕捞结合分子对接技术快速筛选铁皮小檗中α-葡萄糖苷酶抑制配体。

IF 3.3 2区农林科学 Q1 AGRICULTURE, MULTIDISCIPLINARY

Journal of the Science of Food and Agriculture Pub Date : 2025-03-27 DOI:10.1002/jsfa.14223

Bing-Rui Liu, Wen-Xiang Hu, Hai-Jie Li, Jian-Kun Yan, Xi-Tong Zhang, Chu Chu, Yan-Shu Zhang

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引用次数: 0

摘要

背景：Alpinia officinarum Hance根茎作为一种药用和食用植物，作为探索膳食α-葡萄糖苷酶抑制剂的天然来源，越来越受到人们的关注。基于磁珠的配体钓鱼技术在加速鉴定复杂植物提取物中的生物活性成分方面显示出巨大的前景。然而，不同醛活化磁珠的固定化效率和稳定性尚不清楚。此外，非特异性结合阻碍了抑制性配体的表征。结果：分别合成了3碳连接体长度（AGNTC-3MB）和21碳连接体长度（AGNTC-21MB）载体上的固定化酶。当MBs-C21与α-葡萄糖苷酶的质量比为10:1时，固定化效率最高，为91.13±0.40%。AGNTC-21MB的催化活性比AGNTC-3MB高4 ~ 8倍。此外，56天后，AGNTC-21MB的催化活性保持在73.4-90.3%，比AGNTC-3MB（18.2-32.2%）更稳定。在一项概念验证研究中，基于agntc - 21mb的配体捕捞导致了12个配体的鉴定。其中,两个黄酮类化合物——山柰酚(1)galangin(6)和三个diarylheptanoids - 7 (4-hydroxyphenyl) 1-phenyl-4-hepten-3-one (9), 7 - (4-hydroxy-3-methoxyphenyl) 1-henylhept-4-en-3-one(11),和1,7-diphenyl-4-hepten-3-one(15) -α方面表现出显著的葡糖苷酶抑制活性,IC50值范围为23.6±0.7,146.2±3.8μl - 1摩尔和显示一个混合型行为Ki值从42.6±2.0,786.0±13.9μ摩尔l - 1。分子对接表明，化合物6、9、11和15通过氢键、静电和疏水相互作用与α-葡萄糖苷酶结合。结论：连接体长度为21碳的醛活化磁珠和AGNTC-21MB在固定化效率、酶活性和稳定性方面均优于AGNTC-3MB。基于agntc - 21mb的配体钓鱼技术结合高效液相色谱-四极杆飞行时间质谱技术和分子对接技术，为分析巴纳姆抗糖尿病成分提供了有效、可靠的生物分析技术平台。黄酮类化合物和二芳基庚烷类化合物对甲醇提取物α-葡萄糖苷酶的抑制作用起主要作用。药理学和化学特征支持进一步的研究，目的是将officinarum开发成预防和治疗2型糖尿病及相关并发症的功能性食品。©2025化学工业协会。

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Magnetic beads-based ligand fishing for rapid screening of dietary α-glucosidase inhibitory ligands from the rhizome of Alpinia officinarum Hance combined with molecular docking.

Background: The rhizome of Alpinia officinarum Hance, considered as a medicinal and edible plant, is gathering increasing attention as a natural source for exploring dietary α-glucosidase inhibitors. Magnetic beads-based ligand fishing has shown great promise for accelerating identification of bioactive constituents from complex plant extracts. However, immobilization efficiency and stability when using different aldehyde-activated magnetic beads is still unclear. Moreover, non-specific binding hampers characterization of inhibitory ligands.

Results: Immobilized enzymes on 3-carbon linker length (AG_NTC-3MB) and 21-carbon linker length (AG_NTC-21MB) supports were synthesized, respectively. The highest immobilization efficiency of 91.13 ± 0.40% was observed when the mass ratio of MBs-C21 to α-glucosidase was 10:1. The catalytic activity of AG_NTC-21MB was four- to eight-fold higher than that of AG_NTC-3MB. Additionally, after 56 days, the catalytic activity of AG_NTC-21MB retained 73.4-90.3% activity - more stable than AG_NTC-3MB (18.2-32.2%). In a proof-of-concept study, AG_NTC-21MB-based ligand fishing led to the identification of 12 ligands. Among them, two flavonoids - kaempferol (1), galangin (6) - and three diarylheptanoids - 7-(4-hydroxyphenyl)-1-phenyl-4-hepten-3-one (9), 7-(4-hydroxy-3-methoxyphenyl)-1-henylhept-4-en-3-one (11), and 1,7-diphenyl-4-hepten-3-one (15) - exhibited significant α-glucosidase inhibitory activity, with IC₅₀ values in the range of 23.6 ± 0.7 to 146.2 ± 3.8 μmol L^-1, and showing a mixed-type behavior with K_i values ranging from 42.6 ± 2.0 to 786.0 ± 13.9 μmol L^-1. Molecular docking showed compounds 6, 9, 11, and 15 bind with α-glucosidase by H-bonds, electrostatic and hydrophobic interactions.

Conclusion: Aldehyde-activated magnetic beads with 21-carbon linker length and AG_NTC-21MB are superior to AG_NTC-3MB in terms of immobilized efficiency, enzymatic activity, and stability. AG_NTC-21MB-based ligand fishing combined with high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry and molecular docking constitute an effective and robust bioanalytical technology platform for analyzing antidiabetic composition in A. officinarum. Flavonoids and diarylheptanoids are responsible for the α-glucosidase inhibitory effect of the methanolic A. officinarum extract. The pharmacological and chemical profiles support further research with the aim of developing A. officinarum into functional food for prevention and management of type 2 diabetes and related complications. © 2025 Society of Chemical Industry.

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来源期刊

Journal of the Science of Food and Agriculture 工程技术-农业综合

CiteScore

8.10

自引率

4.90%

发文量

634

审稿时长

3.1 months

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