Skip to main content

Advertisement

SpringerLink
Log in

Ligand fishing with cellular membrane-coated cellulose filter paper: a new method for screening of potential active compounds from natural products

  • Paper in Forefront
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Ligand fishing is a widely used approach for screening active compounds from natural products. Recently, cell membrane (CM) as affinity ligand has been applied in ligand fishing, including cell membrane chromatography (CMC) and CM-coated magnetic bead. However, these methods possess many weaknesses, including complicated preparation processes and time-consuming operation. In this study, cheap and easily available cellulose filter paper (CFP) was selected as carrier of CM and used to fabricate a novel CM-coated CFP (CMCFP) for the first time. The type of CFP was optimized according to the amount of immobilized protein, and the immobilization of CM onto CFP by the insertion and self-fusion process was verified by confocal imaging. The CMCFP exhibited good selectivity and stability and was used for fishing potentially active compounds from extracts of Angelica dahurica. Three potentially active compounds, including bergapten, pabulenol, and imperatorin, were fished out and identified. The traditional Chinese medicine systems pharmacology database and analysis platform was used to build an active compound-target protein network, and accordingly, the gamma-aminobutyric acid receptor subunit alpha-1 (GABRA1) was deduced as potential target of CM for the active compounds of Angelica dahurica. Molecular docking was performed to evaluate the interaction between active compounds and GABRA1, and bergapten was speculated as a new potentially active compound. Compared with other methods, the fishing assay based on CMCFP was more effective, simpler, and cheaper.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Tu Y. The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine. Nat Med. 2011;17:1217–20.

    Article  CAS  PubMed  Google Scholar 

  2. Wang Y, Fan X, Qu H, Gao X, Cheng Y. Strategies and techniques for multi-component drug design from medicinal herbs and traditional Chinese medicine. Curr Top Med Chem. 2012;12(12):1356–62.

    Article  CAS  PubMed  Google Scholar 

  3. Wang Z, Li X, Chen M, Liu F, Han C, Kong L, et al. A strategy for screening of α-glucosidase inhibitors from Morus alba root bark based on the ligand fishing combined with high-performance liquid chromatography mass spectrometer and molecular docking. Talanta. 2018;180:337–45.

    Article  CAS  PubMed  Google Scholar 

  4. Cieśla Ł, Moaddel R. Comparison of analytical techniques for the identification of bioactive compounds from natural products. Nat Prod Rep. 2016;33(10):1131–45.

    Article  PubMed  Google Scholar 

  5. Hage DS, Anguizola JA, Bi C, Li R, Matsuda R, Papastavros E, et al. Pharmaceutical and biomedical applications of affinity chromatography: recent trends and developments. J Pharm Biomed Anal. 2012;69:93–105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Zhuo R, Liu H, Liu N, Wang Y. Ligand fishing: a remarkable strategy for discovering bioactive compounds from complex mixture of natural products. Molecules. 2016;21(11):1516–31.

    Article  CAS  PubMed Central  Google Scholar 

  7. Ding X, Cao Y, Yuan Y, Gong Z, Liu Y, Zhao L, et al. Development of APTES-decorated HepG2 cancer stem cell membrane chromatography for screening active components from Salvia miltiorrhiza. Anal Chem. 2016;88(24):12081–9.

    Article  CAS  PubMed  Google Scholar 

  8. Li F, Zhang Y, Qiu D, Kang J. Screening of epidermal growth factor receptor inhibitors in natural products by capillary electrophoresis combined with high performance liquid chromatography–tandem mass spectrometry. J Chromatogr A. 2015;1400:117–23.

    Article  CAS  PubMed  Google Scholar 

  9. Schejbal J, Řemínek R, Zeman L, Mádr A, Glatz Z. On-line coupling of immobilized cytochrome P450 microreactor and capillary electrophoresis: a promising tool for drug development. J Chromatogr A. 2016;1437:234–40.

    Article  CAS  PubMed  Google Scholar 

  10. Yin Z, Zhao W, Tian M, Zhang Q, Guo L, Yang L. A capillary electrophoresis-based immobilized enzyme reactor using graphene oxide as a support via layer by layer electrostatic assembly. Analyst. 2014;139(8):1973–9.

    Article  CAS  PubMed  Google Scholar 

  11. Moaddel R, Marszałł MP, Bighi F, Yang Q, Duan X, Wainer IW. Automated ligand fishing using human serum albumin-coated magnetic beads. Anal Chem. 2007;79(14):5414–7.

    Article  CAS  PubMed  Google Scholar 

  12. Song HP, Chen J, Hong JY, Hao H, Qi LW, Lu J, et al. A strategy for screening of high-quality enzyme inhibitors from herbal medicines based on ultrafiltration LC-MS and in silico molecular docking. Chem Commun. 2015;51(8):1494–7.

    Article  CAS  Google Scholar 

  13. Hu Y, Fu A, Miao Z, Zhang X, Wang T, Kang A, et al. Fluorescent ligand fishing combination with in-situ imaging and characterizing to screen Hsp 90 inhibitors from Curcuma longa L. based on InP/ZnS quantum dots embedded mesoporous nanoparticles. Talanta. 2018;178:258–67.

    Article  CAS  PubMed  Google Scholar 

  14. Wang H, Zhao X, Wang S, Tao S, Ai N, Wang Y. Fabrication of enzyme-immobilized halloysite nanotubes for affinity enrichment of lipase inhibitors from complex mixtures. J Chromatogr A. 2015;1392:20–7.

    Article  CAS  PubMed  Google Scholar 

  15. Hou G, Niu J, Song F, Liu Z, Liu S. Studies on the interactions between ginsenosides and liposome by equilibrium dialysis combined with ultrahigh performance liquid chromatography-tandem mass spectrometry. J Chromatogr B. 2013;923-924:1–7.

    Article  CAS  Google Scholar 

  16. Chen L, Wang X, Liu Y, Di X. Dual-target screening of bioactive components from traditional Chinese medicines by hollow fiber-based ligand fishing combined with liquid chromatography–mass spectrometry. J Pharm Biomed Anal. 2017;143:269–76.

    Article  CAS  PubMed  Google Scholar 

  17. de Almeida FG, Vanzolini KL, Cass QB. Angiotensin converting enzyme immobilized on magnetic beads as a tool for ligand fishing. J Pharm Biomed Anal. 2017;132:159–64.

    Article  CAS  PubMed  Google Scholar 

  18. Overington JP, Al-Lazikani B, Hopkins AL. How many drug targets are there? Nat Rev Drug Discov. 2006;5:993–6.

    Article  CAS  PubMed  Google Scholar 

  19. Hou X, Wang S, Zhang T, Ma J, Zhang J, Zhang Y, et al. Recent advances in cell membrane chromatography for traditional Chinese medicines analysis. J Pharm Biomed Anal. 2014;101:141–50.

    Article  CAS  PubMed  Google Scholar 

  20. Xu L, Xu B, Zhao ZY, Yang HP, Tang C, Dong LY, et al. Preparation and characterization of micro-cell membrane chromatographic column with N-hydroxysuccinimide group-modified silica-based porous layer open tubular capillary. J Chromatogr A. 2017;1516:125–30.

    Article  CAS  PubMed  Google Scholar 

  21. Dong ZB, Li SP, Hong M, Zhu Q. Hypothesis of potential active components in Angelica sinensis by using biomembrane extraction and high performance liquid chromatography. J Pharm Biomed Anal. 2005;38(4):664–9.

    Article  CAS  PubMed  Google Scholar 

  22. Tang C, Mao R, Liu F, Yu Y, Xu L, Zhang Y. Ligand fishing with cellular membrane-coated magnetic beads: a new method for the screening of potentially active compounds from natural products. Chromatographia. 2017;80(10):1517–25.

    Article  CAS  Google Scholar 

  23. Ma J, Wang C, Wei Y. Polyethyleneimine-facilitated high-capacity boronate affinity membrane and its application for the adsorption and enrichment of cis-diol-containing molecules. RSC Adv. 2016;6(49):43648–55.

    Article  CAS  Google Scholar 

  24. Yuan LM, Ma W, Xu M, Zhao HL, Li YY, Wang RL, et al. Optical resolution and mechanism using enantioselective cellulose, sodium alginate and hydroxypropyl-β-cyclodextrin membranes. Chirality. 2017;29(6):315–24.

    Article  CAS  PubMed  Google Scholar 

  25. Wang X, Xu L, Mao R, Zhao X, Xu B, Tang C, et al. An insertion/self-fusion mechanism for cell membrane immobilization on porous silica beads to fabricate biomimic carriers. Biomater Sci. 2017;5(7):1334–41.

    Article  PubMed  Google Scholar 

  26. Singer SJ, Nicolson GL. The fluid mosaic model of the structure of cell membranes. Science. 1972;175(4023):720–31.

    Article  CAS  PubMed  Google Scholar 

  27. Ru J, Li P, Wang J, Zhou W, Li B, Huang C, et al. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. Aust J Chem. 2014;6(1):13–8.

    Google Scholar 

  28. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498–504.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hsin K-Y, Matsuoka Y, Asai Y, Kamiyoshi K, Watanabe T, Kawaoka Y, et al. systemsDock: a web server for network pharmacology-based prediction and analysis. Nucleic Acids Res. 2016;44(W1):W507–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Hsin KY, Ghosh S, Kitano H. Combining machine learning systems and multiple docking simulation packages to improve docking prediction reliability for network pharmacology. PLoS One. 2014;8(12):e83922.

    Article  CAS  Google Scholar 

  31. Lee KS, Tsien RW. Mechanism of calcium channel blockade by verapamil, D600, diltiazem and nitrendipine in single dialysed heart cells. Nature. 1983;302:790–4.

    Article  CAS  PubMed  Google Scholar 

  32. He L, Wang S, Geng X. Coating and fusing cell membranes onto a silica surface and their chromatographic characteristics. Chromatographia. 2001;54(1):71–6.

    Article  CAS  Google Scholar 

  33. Du H, He J, Wang S, He L. Investigation of calcium antagonist–L-type calcium channel interactions by a vascular smooth muscle cell membrane chromatography method. Anal Bioanal Chem. 2010;397(5):1947–53.

    Article  CAS  PubMed  Google Scholar 

  34. Wubshet SG, Brighente IMC, Moaddel R, Staerk D. Magnetic ligand fishing as a targeting tool for HPLC-HRMS-SPE-NMR: α-glucosidase inhibitory ligands and alkylresorcinol glycosides from eugenia catharinae. J Nat Prod. 2015;78(11):2657–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Pochet L, Heus F, Jonker N, Lingeman H, Smit AB, Niessen WMA, et al. Online magnetic bead based dynamic protein affinity selection coupled to LC–MS for the screening of acetylcholine binding protein ligands. J Chromatogr B. 2011;879(20):1781–8.

    Article  CAS  Google Scholar 

  36. Xie Y, Chen Y, Lin M, Wen J, Fan G, Wu Y. High-performance liquid chromatographic method for the determination and pharmacokinetic study of oxypeucedanin hydrate and byak-angelicin after oral administration of Angelica dahurica extracts in mongrel dog plasma. J Pharm Biomed Anal. 2007;44(1):166–72.

    Article  CAS  PubMed  Google Scholar 

  37. Li B, Zhang X, Wang J, Zhang L, Gao B, Shi S, et al. Simultaneous characterisation of fifty coumarins from the roots of angelica dahurica by off-line two-dimensional high-performance liquid chromatography coupled with electrospray ionisation tandem mass spectrometry. Phytochem Anal. 2014;25(3):229–40.

    Article  CAS  PubMed  Google Scholar 

  38. He JY, Zhang W, He LC, Cao YX. Imperatorin induces vasodilatation possibly via inhibiting voltage dependent calcium channel and receptor-mediated Ca2+ influx and release. Eur J Pharmacol. 2007;573(1):170–5.

    Article  CAS  PubMed  Google Scholar 

  39. Schofield PR, Pritchett DB, Sontheimer H, Kettenmann H, Seeburg PH. Sequence and expression of human GABAA receptor α1 and β1 subunits. FEBS Lett. 1989;244(2):361–4.

    Article  CAS  PubMed  Google Scholar 

  40. Horiuchi Y, Nakayama J, Ishiguro H, Ohtsuki T, Detera-Wadleigh SD, Toyota T, et al. Possible association between a haplotype of the GABA-A receptor alpha 1 subunit gene (GABRA1) and mood disorders. Biol Psychiatry. 2004;55(1):40–5.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank Prof. H. Duan of Tianjin Medical University and Prof. L. He and Prof. S. Wang of Xi’an Jiaotong University for their valuable help on this work.

Funding

This work was financially supported by the National Natural Science Foundation of China (Grant Nos. 21605114, 81402889, 81303191), 131 innovative talents training project in Tianjin, Tianjin Municipal Administration of Traditional Chinese Medicine (Grant No. 2017077), and Tianjin Institute of Higher Vocational Education (Grant No. VII308).

Author information

Author notes

  1. Liang Xu and Cheng Tang contributed equally to this work.

Authors and Affiliations

  1. Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnosis, School of Pharmacy, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300072, China

    Liang Xu, Cheng Tang, Xin Li, Xiaofan Li, Huiping Yang, Ruizhi Mao, Wanqing Li & Xianhua Wang

  2. Tianjin Medical College, Tianjin, 300222, China

    Liang Xu, Jiyang Liu & Yalong Li

  3. People’s Hospital of Tongliangqu, Chongqing, 402560, China

    Ruizhi Mao

  4. School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 61 Yuquan Road, Nankai District, Tianjin, 300193, China

    Jiahui He & Xuefeng Xiao

  5. Acchrom Technologies Co., Lid., Beijing, 100020, China

    Jiahui He

  6. Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Chaoyang District, Beijing, 100029, China

    Shuobo Shi

Authors
  1. Liang Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cheng Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xin Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaofan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Huiping Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ruizhi Mao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jiahui He
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Wanqing Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jiyang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yalong Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Shuobo Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Xuefeng Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Xianhua Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Xuefeng Xiao or Xianhua Wang.

Ethics declarations

The procedure about rabbit was approved by Animal Ethics Committee, Tianjin Medical University, Tianjin, China. All the experiments on rabbits were performed in compliance with the guide of care and use of laboratory animals.

Conflict of interest

The authors declare that they no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(PDF 3137 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xu, L., Tang, C., Li, X. et al. Ligand fishing with cellular membrane-coated cellulose filter paper: a new method for screening of potential active compounds from natural products. Anal Bioanal Chem 411, 1989–2000 (2019). https://doi.org/10.1007/s00216-019-01662-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-019-01662-z

Keywords

Search

Navigation