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A fluorescence strategy for monitoring α-glucosidase activity and screening its inhibitors from Chinese herbal medicines based on Cu nanoclusters with aggregation-induced emission

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Abstract

Herein, the self-assembly of 1-dodecanethiol-capped Cu nanoclusters (DT-Cu NCs) is obtained by annealing of dibenzyl ether solution of nanoclusters. These aggregates are composed of small clusters and emit a high level of aggregation-induced emission (AIE) in water. Based on the quenching effect of 4-nitrophenol (4-NP) on DT-Cu NCs, a fluorescence strategy is developed to monitor α-glucosidase (α-Glu) activity and screen its inhibitors from Chinese herbal medicines. 4-Nitrophenyl-α-D-glucopyranoside (NGP) is selected as the substrate, which is further hydrolyzed to yield 4-NP through the catalysis of α-Glu. The quenching efficiency is positively correlated to the concentration of α-Glu. Furthermore, the inhibitory effects of the extracts from four Chinese herbal medicines (i.e., the rind of Punica granatum L., Momordica grosvenorii Swingle., Crataegus pinnatifida Bge., and Lycium barbarum L.) on the α-Glu activity have been studied. The IC50 values of extracts from the rind of Punica granatum L. and Momordica grosvenorii Swingle are 0.23 and 0.37 g/L, respectively, so they show obvious inhibitory effects on α-Glu. The extracts of Crataegus pinnatifida Bge. and Lycium barbarum L. exhibit relatively weak inhibitory effects. Hence, the proposed strategy can be applicable for screening α-Glu inhibitors from Chinese herbal medicines. Last but not the least, by immobilizing DT-Cu NCs into agarose hydrogels in polyethylene tubes, a visual device is fabricated to screen α-Glu inhibitors with high throughput and sensitivity.

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References

  1. Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 2018;14(2):88–98. https://doi.org/10.1038/nrendo.2017.151.

    Article  PubMed  Google Scholar 

  2. Kurihara H, Ando J, Hatano M, Kawabata J. Sulfoquinovosyldiacylglycerol as an α-glucosidase inhibitor. Bioorg Med Chem Lett. 1995;5(12):1241–4. https://doi.org/10.1016/0960-894X(95)00196-Z.

    Article  CAS  Google Scholar 

  3. Van De Laar FA, Lucassen PL, Akkermans RP, Van De Lisdonk EH, Rutten GE, Van Weel C. α-Glucosidase inhibitors for patients with type 2 diabetes: results from a Cochrane systematic review and meta-analysis. Diabetes Care. 2005;28(1):154–63. https://doi.org/10.2337/diacare.28.1.154.

    Article  PubMed  Google Scholar 

  4. Kong W, Wu D, Xia L, Chen X, Li G, Qiu N, et al. Carbon dots for fluorescent detection of alpha-glucosidase activity using enzyme activated inner filter effect and its application to anti-diabetic drug discovery. Anal Chim Acta. 2017;973:91–9. https://doi.org/10.1016/j.aca.2017.03.050.

    Article  CAS  PubMed  Google Scholar 

  5. Tang C, Qian Z, Qian Y, Huang Y, Zhao M, Ao H, et al. A fluorometric and real-time assay for α-glucosidase activity through supramolecular self-assembly and its application for inhibitor screening. Sensors Actuators B Chem. 2017;245:282–9. https://doi.org/10.1016/j.snb.2017.01.150.

    Article  CAS  Google Scholar 

  6. Mondal A, Jana NR. Fluorescent detection of cholesterol using beta-cyclodextrin functionalized graphene. Chem Commun. 2012;48(58):7316–8. https://doi.org/10.1039/c2cc33410k.

    Article  CAS  Google Scholar 

  7. Hu QD, Tang GP, Chu PK. Cyclodextrin-based host-guest supramolecular nanoparticles for delivery: from design to applications. Acc Chem Res. 2014;47(7):2017–25. https://doi.org/10.1021/ar500055s.

    Article  CAS  PubMed  Google Scholar 

  8. Munir S, Park SY. The development of a cholesterol biosensor using a liquid crystal/aqueous interface in a SDS-included beta-cyclodextrin aqueous solution. Anal Chim Acta. 2015;893:101–7. https://doi.org/10.1016/j.aca.2015.08.051.

    Article  CAS  PubMed  Google Scholar 

  9. Guo Y, Cao F, Lei X, Mang L, Cheng S, Song J. Fluorescent copper nanoparticles: recent advances in synthesis and applications for sensing metal ions. Nanoscale. 2016;8(9):4852–63. https://doi.org/10.1039/c6nr00145a.

    Article  CAS  PubMed  Google Scholar 

  10. Jia X, Li J, Wang E. Cu nanoclusters with aggregation induced emission enhancement. Small. 2013;9(22):3873–9. https://doi.org/10.1002/smll.201300896.

    Article  CAS  PubMed  Google Scholar 

  11. Wang C, Cheng H, Huang Y, Xu Z, Lin H, Zhang C. Facile sonochemical synthesis of pH-responsive copper nanoclusters for selective and sensitive detection of Pb2+ in living cells. Analyst. 2015;140(16):5634–9. https://doi.org/10.1039/C5AN00741K.

    Article  CAS  PubMed  Google Scholar 

  12. Jia X, Yang X, Li J, Li D, Wang E. Stable Cu nanoclusters: from an aggregation-induced emission mechanism to biosensing and catalytic applications. Chem Commun. 2014;50(2):237–9. https://doi.org/10.1039/c3cc47771a.

    Article  CAS  Google Scholar 

  13. Zhao M, Feng H, Han J, Ao H, Qian Z. Multi-stimuli responsive copper nanoclusters with bright red luminescence for quantifying acid phosphatase activity via redox-controlled luminescence switch. Anal Chim Acta. 2017;984:202–10. https://doi.org/10.1016/j.aca.2017.06.046.

    Article  CAS  PubMed  Google Scholar 

  14. Li Z, Guo S, Lu C. A highly selective fluorescent probe for sulfide ions based on aggregation of Cu nanocluster induced emission enhancement. Analyst. 2015;140(8):2719–25. https://doi.org/10.1039/C5AN00017C.

    Article  CAS  PubMed  Google Scholar 

  15. Lin YJ, Chen PC, Yuan Z, Ma JY, Chang HT. The isomeric effect of mercaptobenzoic acids on the preparation and fluorescence properties of copper nanoclusters. Chem Commun. 2015;51(60):11983–6. https://doi.org/10.1039/c5cc02342d.

    Article  CAS  Google Scholar 

  16. Huang Y, Liu W, Feng H, Ye Y, Tang C, Ao H, et al. Luminescent nanoswitch based on organic-phase copper nanoclusters for sensitive detection of trace amount of water in organic solvents. Anal Chem. 2016;88(14):7429–34. https://doi.org/10.1021/acs.analchem.6b02149.

    Article  CAS  PubMed  Google Scholar 

  17. Gao M, Tang BZ. Fluorescent sensors based on aggregation-induced emission: recent advances and perspectives. ACS Sensors. 2017;2(10):1382–99. https://doi.org/10.1021/acssensors.7b00551.

    Article  CAS  PubMed  Google Scholar 

  18. Qu F, Xia W, Xia L, You J, Han W. A ratiometric detection of heparin with high sensitivity based on aggregation-enhanced emission of gold nanoclusters triggered by silicon nanoparticles. Talanta. 2019;193:37–43. https://doi.org/10.1016/j.talanta.2018.09.098.

    Article  CAS  PubMed  Google Scholar 

  19. Wu Z, Liu J, Gao Y, Liu H, Li T, Zou H, et al. Assembly-induced enhancement of Cu nanoclusters luminescence with mechanochromic property. J Am Chem Soc. 2015;137(40):12906–13. https://doi.org/10.1021/jacs.5b06550.

    Article  CAS  PubMed  Google Scholar 

  20. Parker AJ, Brody D. 772. Solvation of ions. Part IV. The electronic absorption spectra of some group VI anions and their conjugate acids in protic and dipolar aprotic solvents. J Chem Soc. 1963:4061–8. https://doi.org/10.1039/JR9630004061.

  21. Ai L, Jiang W, Liu Z, Liu J, Gao Y, Zou H, et al. Engineering a red emission of copper nanocluster self-assembly architectures by employing aromatic thiols as capping ligands. Nanoscale. 2017;9(34):12618–27. https://doi.org/10.1039/C7NR03985A.

    Article  CAS  PubMed  Google Scholar 

  22. Min J, Wang F, Cai Y, Liang S, Zhang Z, Jiang X. Azeotropic distillation assisted fabrication of silver nanocages and their catalytic property for reduction of 4-nitrophenol. Chem Commun. 2014;51(4):761–4. https://doi.org/10.1039/C4CC07629J.

    Article  CAS  Google Scholar 

  23. Zhao M, Qian Z, Zhong M, Chen Z, Ao H, Feng H. Fabrication of stable and luminescent copper nanocluster-based AIE particles and their application in β-galactosidase activity assay. ACS Appl Mater Interfaces. 2017;9(38):32887–95. https://doi.org/10.1021/acsami.7b09659.

    Article  CAS  PubMed  Google Scholar 

  24. Han L, Liu SG, Liang JY, Ju YJ, Li NB, Luo HQ. pH-mediated reversible fluorescence nanoswitch based on inner filter effect induced fluorescence quenching for selective and visual detection of 4-nitrophenol. J Hazard Mater. 2019;362:45–52. https://doi.org/10.1016/j.jhazmat.2018.09.025.

    Article  CAS  PubMed  Google Scholar 

  25. Zhang J, Zhou R, Tang D, Hou X, Wu P. Optically-active nanocrystals for inner filter effect-based fluorescence sensing: achieving better spectral overlap. Trac-Trend Anal Chem. 2019;110:183–90. https://doi.org/10.1016/j.trac.2018.11.002.

    Article  CAS  Google Scholar 

  26. Qu F, Sun C, Lv X, You J. A terbium-based metal-organic framework@gold nanoparticle system as a fluorometric probe for aptamer based determination of adenosine triphosphate. Microchim Acta. 2018;185(8):359. https://doi.org/10.1007/s00604-018-2888-1.

    Article  CAS  Google Scholar 

  27. Guo X, Deng L, Wang J. Oligonucleotide-stabilized silver nanoclusters as fluorescent probes for sensitive detection of hydroquinone. RSC Adv. 2013;3(2):401–7. https://doi.org/10.1039/C2RA21615A.

    Article  CAS  Google Scholar 

  28. Zhang X, Wu FG, Liu P, Gu N, Chen Z. Enhanced fluorescence of gold nanoclusters composed of HAuCl4 and histidine by glutathione: glutathione detection and selective cancer cell imaging. Small. 2014;10(24):5170–7. https://doi.org/10.1002/smll.201401658.

    Article  CAS  PubMed  Google Scholar 

  29. Wang HB, Chen Y, Li Y, Liu YM. A sensitive fluorescence sensor for glutathione detection based on MnO2 nanosheets–copper nanoclusters composites. RSC Adv. 2016;6(83):79526–32. https://doi.org/10.1039/C6RA17850B.

    Article  CAS  Google Scholar 

  30. Zhang J, Liu Y, Wang X, Chen Y, Li G. Electrochemical assay of alpha-glucosidase activity and the inhibitor screening in cell medium. Biosens Bioelectron. 2015;74:666–72. https://doi.org/10.1016/j.bios.2015.07.023.

    Article  CAS  PubMed  Google Scholar 

  31. Li J, He G, Wang B, Shi L, Gao T, Li G. Fabrication of reusable electrochemical biosensor and its application for the assay of alpha-glucosidase activity. Anal Chim Acta. 2018;1026:140–6. https://doi.org/10.1016/j.aca.2018.04.015.

    Article  CAS  PubMed  Google Scholar 

  32. Xi M, Hai C, Tang H, Chen M, Fang K, Liang X. Antioxidant and antiglycation properties of total saponins extracted from traditional Chinese medicine used to treat diabetes mellitus. Phytother Res. 2008;22(2):228–37. https://doi.org/10.1002/ptr.2297.

    Article  CAS  PubMed  Google Scholar 

  33. Tong XL, Dong L, Chen L, Zhen Z. Treatment of diabetes using traditional Chinese medicine: past, present and future. Am J Chin Med. 2012;40(5):877–86. https://doi.org/10.1142/S0192415X12500656.

    Article  PubMed  Google Scholar 

  34. Kim KY, Nam KA, Kurihara H, Kim SM. Potent alpha-glucosidase inhibitors purified from the red alga Grateloupia elliptica. Phytochemistry. 2008;69(16):2820–5. https://doi.org/10.1016/j.phytochem.2008.09.007.

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by the National Natural Science Foundation of China (No. 21775088, 21705095), the Natural Science Foundation of Shandong Province, China (ZR2019QB010), and the Scientific Research Foundation of Qufu Normal University (BSQD20130117).

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Authors and Affiliations

  1. Key Laboratory of Life-Organic Analysis of Shandong Province, School of Chemistry and Chemical Engineering, Qufu Normal University, Jining, 272000, Shandong, China

    Cong Li, Yuqiu Zi, Dawei Xu, Fei Qu & Xian-En Zhao

  2. Key Laboratory of Green Natural Products and Pharmaceutical Intermediates in Colleges and Universities of Shandong Province, School of Chemistry and Chemical Engineering, Qufu Normal University, Jining, 272000, Shandong, China

    Cong Li, Yuqiu Zi, Dawei Xu, Fei Qu & Xian-En Zhao

  3. Department of Physical and Chemical Testing, Shandong Center for Disease Control and Prevention, Jinan, 250014, Shandong, China

    Dafeng Jiang

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  1. Cong Li
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Correspondence to Fei Qu or Xian-En Zhao.

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The human serum sample experiments were performed in accordance with the guidelines from the Ethical Committee, Qufu Normal University. All serum samples were obtained from healthy volunteers with their informed consent. All studies were approved by the Ethical Committee of Qufu Normal University.

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Li, C., Zi, Y., Xu, D. et al. A fluorescence strategy for monitoring α-glucosidase activity and screening its inhibitors from Chinese herbal medicines based on Cu nanoclusters with aggregation-induced emission. Anal Bioanal Chem 413, 2553–2563 (2021). https://doi.org/10.1007/s00216-021-03214-w

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