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.

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

{"title":"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.","authors":"Bing-Rui Liu, Wen-Xiang Hu, Hai-Jie Li, Jian-Kun Yan, Xi-Tong Zhang, Chu Chu, Yan-Shu Zhang","doi":"10.1002/jsfa.14223","DOIUrl":null,"url":null,"abstract":"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 (AGNTC-3MB) and 21-carbon linker length (AGNTC-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 AGNTC-21MB was four- to eight-fold higher than that of AGNTC-3MB. Additionally, after 56 days, the catalytic activity of AGNTC-21MB retained 73.4-90.3% activity - more stable than AGNTC-3MB (18.2-32.2%). In a proof-of-concept study, AGNTC-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 Ki 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 AGNTC-21MB are superior to AGNTC-3MB in terms of immobilized efficiency, enzymatic activity, and stability. AGNTC-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.","PeriodicalId":17725,"journal":{"name":"Journal of the Science of Food and Agriculture","volume":" ","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the Science of Food and Agriculture","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.1002/jsfa.14223","RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"AGRICULTURE, MULTIDISCIPLINARY","Score":null,"Total":0}

引用次数: 0

Abstract

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.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

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

期刊介绍： The Journal of the Science of Food and Agriculture publishes peer-reviewed original research, reviews, mini-reviews, perspectives and spotlights in these areas, with particular emphasis on interdisciplinary studies at the agriculture/ food interface. Published for SCI by John Wiley & Sons Ltd. SCI (Society of Chemical Industry) is a unique international forum where science meets business on independent, impartial ground. Anyone can join and current Members include consumers, business people, environmentalists, industrialists, farmers, and researchers. The Society offers a chance to share information between sectors as diverse as food and agriculture, pharmaceuticals, biotechnology, materials, chemicals, environmental science and safety. As well as organising educational events, SCI awards a number of prestigious honours and scholarships each year, publishes peer-reviewed journals, and provides Members with news from their sectors in the respected magazine, Chemistry & Industry . Originally established in London in 1881 and in New York in 1894, SCI is a registered charity with Members in over 70 countries.