Skip to main content

Advertisement

SpringerLink
Log in

Spectroscopic investigation on the interaction characteristics and inhibitory activities between baicalin and acetylcholinesterase

  • Original Research
  • Published:
Medicinal Chemistry Research Aims and scope Submit manuscript

Abstract

Restoring neurotransmitter acetylcholine (ACh) levels by inhibiting acetylcholinesterase (AChE) has become the primary treatment for the cognitive deficits of Alzheimer’s disease. The inhibitory effects of flavonoids on AChE have attracted great interest among researchers, but few reports have focused on the interaction characteristics of inhibitor with AChE. In this work, the interaction of inhibitor baicalin with AChE was studied for the first time by fluorescence spectroscopy coupled with UV spectroscopy and circular dichroism (CD) techniques under near physiological conditions. The fluorescence quenching rate constants and binding constants for baicalin‒AChE system were determined at different temperatures. The fluorescence quenching of AChE by baicalin is due to static quenching and energy transfer. The distance and the binding constant (Ka) between baicalin and AChE were estimated to be 2.85 nm and 9.772 × 104 L mol−1 at 298 K. The results of thermodynamic parameters, ΔH (−174.6 kJ mol−1), ΔS (−489.9 J mol−1 K−1) and ΔG (−28.61 ~ −23.71 kJ mol−1), indicated that van der Waals interaction and hydrogen bonding played a major role for baicalin‒AChE association. Synchronous fluorescence spectral change of AChE showed the binding sites mainly are focused on tryptophan moiety. Circular dichroism spectra showed that baicalin caused a secondary structure change of AChE. Synchronous fluorescence and three-dimensional fluorescence studies showed that the presence of baicalin could change the conformation of AChE during the binding process. Baicalin showed an obvious inhibitory activity, with 1.24 × 10−4 mol L−1 for 50% inhibition of AChE activity (IC50). The in intro studies suggest that the baicalin could decrease catalytic activity of AChE, it is helpful for restoring and rebalancing neurotransmitter ACh levels.

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

Access this article

Log in via an institution

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
Fig. 9

Similar content being viewed by others

References

  • Akao T, Hanada M, Sakashita Y, Sato K, Morita M, Imanaka T (2007) Efflux of baicalin, a flavone glucuronide of Scutellariae Radix, on Caco-2 cells through multidrug resistance-associated protein. J Pharm Pharmacol 59:87–93

    Article  PubMed  CAS  Google Scholar 

  • Anand P, Singh B (2013) A review on cholinesterase inhibitors for Alzheimer's disease. Arch Pharm Res 36(4):375–399

    Article  PubMed  CAS  Google Scholar 

  • Barbero N, Barni E, Barolo C, Quagliotto P, Viscardi G, Napione L, Pavan S, Bussolino F (2009) A study of the interaction between fluorescein sodium salt and bovine serum albumin by steady-state fluorescence. Dyes Pigments 80:307–313

    Article  CAS  Google Scholar 

  • Besley NA, Hirst JD (1999) Theoretical studies toward quantitative protein circular dichroism calculations. J Am Chem Soc 121:9636–9644

    Article  CAS  Google Scholar 

  • Bhattar SL, Kolekar GB, Patil SR (2008) Fluorescence resonance energy transfer between perylene and riboflavin in micellar solution and analytical application on determination of vitamin B2. J Lumin 128(3):306–310

    Article  CAS  Google Scholar 

  • Bi S, Ding L, Tian Y, Song D, Zhou X, Liu X, Zhang HQ (2004) Investigation of the interaction between flavonoids and human serum albumin. J Mol Struct 703(1–3):37–45

    Article  CAS  Google Scholar 

  • Castro A, Martinez A (2001) Peripheral and dual binding site acetylcholinesterase inhibitors: implications in treatment of Alzheimer's disease. Mini-Rev Med Chem 1:267–272

    Article  PubMed  CAS  Google Scholar 

  • Chen L, Fang L, Fang X, Gou S (2010) The new target of acetylcholinesterase inhibitors against Alzheimer′s disease research progress. Chin Pharm J 45:1606–1611

    CAS  Google Scholar 

  • Čolović MB, Krstić DZ, Lazarević-Pašti TD, Tamara D, Bondzic AM, Vasic VM (2013) Acetylcholinesterase inhibitors: pharmacology and toxicology. Curr Neuropharmacol 11:315–335

    Article  PubMed  PubMed Central  Google Scholar 

  • Ding F, Zhao GY, Huang JL, Sun Y, Zhang L (2009) Fluorescence spectroscopic investigation of the interaction between chloramphenicol and lysozyme. Med Chem 44:4083–4089

    CAS  Google Scholar 

  • Dvir H, Silman I, Harel M, Rosenberry TL, Sussman JL (2010) Acetylcholinesterase: from 3D structure to function. Chem Biol Interact 187:10–22

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ellman GL, Courtney KD, Andres Jr V, Featherstone RM (1961) Biochem Pharmacol 7:88–95

    Article  PubMed  CAS  Google Scholar 

  • Goedert M, Spillantini MG (2006) A century of Alzheimer’s disease. Science 314:777–781

    Article  PubMed  CAS  Google Scholar 

  • Guo M, Lu WJ, Li MH, Wang W (2008) Study on the binding interaction between carnitine optical isomer and bovine serum albumin. Eur J Med Chem 43:2140–2148

    Article  PubMed  CAS  Google Scholar 

  • Guo Y, Sun M, Xing Z, Liu Y (1988) Circular dichroism analysis of acetylcholinesterase Acta Biophysica. Sinica 4:211–214

    Google Scholar 

  • Guo XJ, Sun XD, Xu SK (2009) Spectroscopic investigation of the interaction between riboflavin and bovine serum albumin. J Mol Struct 931:55–59

    Article  CAS  Google Scholar 

  • He X, Carter DC (1992) Atomic structure and chemistry of human serum albumin. Nature 358:209–215

    Article  PubMed  CAS  Google Scholar 

  • Hu YJ, Liu Y, Shen XS, Fang XY, Qu SS (2005) Studies on the interaction between 1-hexylcarbamoyl-5-fluorouracil and bovine serum albumin. J Mol Struct 738:143–147

    Article  CAS  Google Scholar 

  • Hu YJ, Liu Y, Zhao RM, Dong JX, Qu SS (2006) Spectroscopic studies on the interaction between methylene blue and bovine serum albumin. J Photochem Photobiol A 179:324–329

    Article  CAS  Google Scholar 

  • Khan I, Muhammad N, Nematullah K, Muhammad S, Said N, Farooq A, Nasiara K, Waqar Ahmad K, Mughal Q, Hanif A, Ihsan Ali K (2010) Structural insights to investigate Conypododiol as a dual cholinesterase inhibitor from Asparagus adscendens. Fitoterapia 81:1020–1025

    Article  PubMed  CAS  Google Scholar 

  • Lackowcz JR (2006) Principles of Fluorescence Spectroscopy, 3rd edn. Plenum Press, New York, pp 277–350

    Book  Google Scholar 

  • Lin CC, Shieh DE (1996) The anti-inflammatory activity of Scutellaria rivularis extracts and its active components, baicalin, baicalein and wogonin. Am J Chin Med 24(1):31–36

    Article  PubMed  CAS  Google Scholar 

  • Lackowicz JR, Weber G (1973) Quenching of protein fluorescence by oxygen: probe for structural fluctuations in macromolecules. Biochem 12:4161–4170

    Article  Google Scholar 

  • Laurents DV, Baldwin RL (1997) Characterization of the unfolding pathway of hen egg white Lysozyme. Biochem 36:1496–1504

    Article  CAS  Google Scholar 

  • Liu X, Chen X, Xiao J, Zhao J (2010) Effect of hydrogenation on ring C of flavonols on their affinity for bovine serum albumin. J Solut Chem 39:533–542

    Article  CAS  Google Scholar 

  • Mallick A, Haldar B, Chattopadhyay N (2005) Spectroscopic investigation on the interaction of ICT probe 3-A. quinolizine with serum albumin. J Phys Chem B 109:14683–14690

    Article  PubMed  CAS  Google Scholar 

  • Maurice RE, Camillo AG (1981) Fluorescence quenching studies with proteins. Anal Biochem 114:199–212

    Article  Google Scholar 

  • Mukherjee PK, Kumar V, Mal M, Houghton PJ (2007) Acetylcholinesterase inhibitors from plants. Phytomedicine 14:289–300

    Article  PubMed  CAS  Google Scholar 

  • Pohanka M (2012) Acetylcholinesterase inhibitors: a patent review (2008–present). Expert Opin Ther Pat 22:871–886

    Article  PubMed  CAS  Google Scholar 

  • Ross PD, Subramanian S (1981) Thermodynamics of protein association reactions: forces contributing to stability. Biochem 20:3096–3102

    Article  CAS  Google Scholar 

  • Savini L, Gaeta A, Fattorusso C, Catalanotti B, Campiani G, Chiasserini L, Pellerano C, Novellino E, McKissic D, Saxena A (2003) Specific targeting of acetylcholinesterase and butyrylcholinesterase recognition sites. rational design of novel, selective, and highly potent cholinesterase inhibitors. J Med Chem 46:1–4

    Article  PubMed  CAS  Google Scholar 

  • Shaikh SMT, Seetharamappa J, Kandagal PB, Ashoka S (2006) Binding of the bioactive component isothipendyl hydrochloride withovine serum albumin. J Mol Struct 786:46–52

    Article  CAS  Google Scholar 

  • Tian J, Liu J, He W, Hu Z, Yao X, Chen X (2004) Probing the binding of scutellarin to human serum albumin by circular dichroism, fluorescence spectroscopy, FTIR, and molecular modeling method. Biomacromolecules 5:1956–1961

    Article  PubMed  CAS  Google Scholar 

  • Trinh N, Hoblyn J, Mohanty S, Mohanty S, Yaffe K (2003) Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer Disease: a meta-analysis. J Am Med Assoc 289:210–216

    Article  CAS  Google Scholar 

  • Tougu V (2001) Acetylcholinesterase: mechanism of catalysis and inhibition. Curr Med Chem 1:155–170

    CAS  Google Scholar 

  • Trynda-Lemiesz L, Karaczyn A, Keppler BK, Kozłowski H (2000) Studies on the interactions between human serum albumin and trans-indazolium (bisindazole) tetrachlororuthenate(III). J Inorg Biochem 78:341–346

    Article  PubMed  CAS  Google Scholar 

  • Wang Q, Jiang H, Chen J, Chen K, Ji R (1998) On the possible reaction pathway for the acylation of AChE-catalyzed hydrolysis of ACh: Semiempirical quantum chemical study. Int J Quantum Chem 70:515–525

    Article  CAS  Google Scholar 

  • Xiao Q, Huang S, Liu Y, Tian FF, Zhu JC (2009) Thermodynamics, conformation and active sites of the binding of Zn-Nd hetero-bimetallic schiff base to bovine serum albumin. J Fluoresc 19:317–326

    Article  PubMed  CAS  Google Scholar 

  • Xie Y, Yang W, Chen X, Xiao J (2014) Inhibition of flavonoids on acetylcholine esterase: binding and structure–activity relationship. Food Funct 5:2582–2589

    Article  PubMed  CAS  Google Scholar 

  • Zhao XC, Liu RT, Chi ZX, Teng Y, Qin P (2010) New insights into the behavior of bovine serum albumin adsorbed onto carbon nanotubes: comprehensive spectroscopic studies. J Phys Chem B 114:5625–5656

    Article  PubMed  CAS  Google Scholar 

  • Zhang ZJ, Li P, Wang Z, Li PT, Zhang WS, Sun ZH, Zhang XJ, Wang YY (2006) A comparative study on the individual and combined effects of baicalin and jasminoidin on focal cerebral ischemia-reperfusion injury. Brain Res 1123:188–195

    Article  PubMed  CAS  Google Scholar 

  • Zhang W, Zhao Y, Bai X, Hui G, Zhao D, Zhao B (2010) Studies on the Interaction for baicalein and baicalin with human serum albumin by spectroscopic methods. Chem J Chin Univ 31:1834–1840

    CAS  Google Scholar 

  • Zhang DB (2010) The screening of alkaloidal acetylcholinesterase inhibitors from medicinal plan. Master Dissertation, Lanzhou University of Technology

  • Zhang LN, Wu FY, Liu AH (2011) Study of the interaction between 2,5-di-[2-(4-hydroxy- phenyl)ethylene]-terephthalonitril and bovine serum albumin by fluorescence spectroscopy. Spectrochim Acta A 79:97–103

    Article  CAS  Google Scholar 

  • Zhang YZ, Chen XX, Dai J, Liu Y (2008) Spectroscopic studies on the interaction of lanthanum(III) 2-oxo-propionic acid salicyloyl hydrazone complex with bovine serum albumin. J Lumin 23:150–156

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the Science Foundation Office of Hebei Province, China (B2014201171).

Author information

Authors and Affiliations

  1. Hebei College of Science and Technology, 071000, Baoding, China

    Mingyan Sun, Ming Su & Hanwen Sun

  2. Key Laboratory of Analytical Science and Technology of Hebei Province, Hebei University, 071002, Baoding, China

    Mingyan Sun & Hanwen Sun

Authors
  1. Mingyan Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ming Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hanwen Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hanwen Sun.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sun, M., Su, M. & Sun, H. Spectroscopic investigation on the interaction characteristics and inhibitory activities between baicalin and acetylcholinesterase. Med Chem Res 27, 1589–1598 (2018). https://doi.org/10.1007/s00044-018-2174-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-018-2174-0

Keywords

Search

Navigation