Skip to main content
Log in

Investigation on the Binding Behavior of Ellagic Acid to Human Serum Albumin in Aqueous Solution

  • Published:
Journal of Solution Chemistry Aims and scope Submit manuscript

Abstract

Ellagic acid (EA), one of the polyphenols in fruits and nuts, has pharmacological activity. To explore binding behavior of EA to protein, human serum albumin (HSA) was chosen and investigated by fluorescence spectroscopy, Fourier transform infrared (FT-IR) spectroscopy and molecular modeling in aqueous solution. Fluorescence titration results indicated that EA effectively quenched the intrinsic fluorescence of HSA by static quenching and the binding process was spontaneous. According to the Scatchard equation, there was only one class of binding sites can bind to HSA, the binding constants at three different temperatures (298, 310 and 318 K) were 8.47 × 104, 7.39 × 104 and 6.00 × 104, respectively. It was found by FT-IR spectra that EA altered HSA secondary structure. Thermodynamic analysis showed that hydrophobic interaction and hydrogen bonds played an important role in stabilizing EA–HSA complex. A molecular docking study suggested that the HSA residues for EA binding located in sub-domain IIA.

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

Access this article

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

Instant access to the full article PDF.

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

Similar content being viewed by others

References

  1. Pfundstein, B., Desouky, S.K.E., Hull, W.E., Haubner, R., Erben, G., Owen, R.W.: Polyphenolic compounds in the fruits of Egyptian medicinal plants (Terminalia bellerica, Terminalia chebula and Terminalia horrida): Characterization, quantitation and determination of antioxidant capacities. Phytochemistry 71, 1132–1148 (2010)

    Article  CAS  Google Scholar 

  2. Daly, T., Ryan, E., Aherne, S.A., O’Grady, M.N., Hayes, J., Allen, P., Kerry, J.P., O’Brien, N.M.: Bioactivity of ellagic acid-, lutein- or sesamol-enriched meat patties assessed using an in vitro digestion and Caco-2 cell model system. Food Res. Int. 43, 753–760 (2010)

    Article  CAS  Google Scholar 

  3. Ginjom, I., Arcy, B.D., Caffin, N., Gidley, M.: Phenolic compound profiles in selected Queensland red wines at all stages of the wine-making process. Food Chem. 125, 823–834 (2011)

    Article  CAS  Google Scholar 

  4. Hayes, J.E., Stepanyan, V., Allen, P., O’Grady, M.N., O’Brien, N.M., Kerry, J.P.: The effect of lutein, sesamol, ellagic acid and olive leaf extract on lipid oxidation and oxymyoglobin oxidation in bovine and porcine muscle model systems. Meat Sci. 83, 201–208 (2009)

    Article  CAS  Google Scholar 

  5. Bakkalbasi, E., Mentes, O., Artik, N.: Food ellagitannins–occurrence, effects of processing and storage. Crit. Rev. Food Sci. 49, 283–293 (2008)

    Article  Google Scholar 

  6. Soong, Y.Y., Barlow, P.J.: Antioxidant activity and phenolic content of selected fruit seeds. Food Chem. 88, 411–417 (2004)

    Article  CAS  Google Scholar 

  7. Soong, Y.Y., Barlow, P.J.: Quantification of gallic acid and ellagic acid from longan (Dimocarpus longan Lour.) seed and mango (Mangifera indica L.) kernel and their effects on antioxidant activity. Food Chem. 97, 524–530 (2006)

    Article  CAS  Google Scholar 

  8. Pari, L., Sivasankari, R.: Effect of ellagic acid on cyclosporine A-induced oxidative damage in the liver of rats. Fund. Clin. Pharmacol. 22, 395–401 (2008)

    Article  CAS  Google Scholar 

  9. Hwang, J.M., Cho, J.S., Kim, T.H., Lee, Y.I.: Ellagic acid protects hepatocytes from damage by inhibiting mitochondrial production of reactive oxygen species. Biomed. Pharmacother. 64, 264–270 (2010)

    Article  CAS  Google Scholar 

  10. Kim, S., Gaber, M.W., Zawaski, J.A., Zhang, F., Richardson, M., Zhang, X.-A., Yang, Y.: The inhibition of glioma growth in vitro and in vivo by a chitosan/ellagic acid composite biomaterial. Biomaterials 30, 4743–4751 (2009)

    Article  CAS  Google Scholar 

  11. Feng, Y., Yang, S.-G., Du, X.-T., Zhang, X., Sun, X.-.X., Zhao, M., Sun, G.-Y., Liu, R.-T.: Ellagic acid promotes Ab42 fibrillization and inhibits Ab42-induced neurotoxicity. Biochem. Biophy. Res. Co. 390, 1250–1254 (2009)

    Article  CAS  Google Scholar 

  12. Yüce, A., Ateşşahin, A., Çeribaş, A.O., Aksakal, M.: Ellagic acid prevents cisplatin induced oxidative stress in liver and heart tissue of rats. Basic Clin. Pharmacol. Toxicol. 101, 345–349 (2007)

    Article  Google Scholar 

  13. Rogerio, A.P., Fontanari, C., Melo, M.C., Ambrosio, S.R., Souza, G.E., Pereira, P.S., Franca, S.C., Costa, F.B., Albuquerque, D.A., Faccioli, L.H.: Anti-inflammatory analgesic and anti-oedematous effects of Lafoensia pacari extract and ellagic acid. J. Pharm. Pharmacol. 58, 1265–1273 (2006)

    Article  CAS  Google Scholar 

  14. Papoutsi, Z., Kassi, E., Chinou, I., Halabalaki, M., Skaltsounis, L.A., Moutsatsou, P.: Walnut extract (Juglans regia L.) and its component ellagic acid exhibit anti-inflammatory activity in human aorta endothelial cells and osteoblastic activity in the cell line KS483. Br. J. Nutr. 99, 715–722 (2008)

    Article  CAS  Google Scholar 

  15. Kaur, S., Grover, I.S., Kumar, S.: Antimutagenic potential of ellagic acid isolated from Terminalia arjuna. Indian J. Exp. Biol. 35, 478–482 (1997)

    CAS  Google Scholar 

  16. Makena, P.S., Chung, K.T.: Effects of various plant polyphenols on bladder carcinogen benzidine-induced mutagenicity. Food Chem. Toxicol. 45, 1899–1909 (2007)

    Article  CAS  Google Scholar 

  17. Cui, F.-L., Qin, L.-X., Zhang, G.-S., Liu, Q.-F., Yao, X.-J., Lei, B.-L.: Interaction of anthracycline disaccharide with human serum albumin: investigation by fluorescence spectroscopic technique and modeling studies. J. Pharmaceut. Biomed. 48, 1029–1036 (2008)

    Article  CAS  Google Scholar 

  18. Mandeville, J.S., Froehlich, E., Tajmir-Riahi, H.A.: Study of curcumin and genistein interactions with human serum albumin. J. Pharmaceut. Biomed. 49, 468–474 (2009)

    Article  CAS  Google Scholar 

  19. Froehlich, E., Mandeville, J.S., Jennings, C.J., Sedaghat-Herati, R., Tajmir-Riahi, H.A.: Dendrimers bind human serum albumin. J. Phys. Chem. B 113, 6986–6993 (2009)

    Article  CAS  Google Scholar 

  20. Charbonneau, D., Beauregard, M., Tajmir-Riahi, H.A.: Structural analysis of human serum albumin complexes with cationic lipids. J. Phys. Chem. B 113, 1777–1784 (2009)

    Article  CAS  Google Scholar 

  21. Herve, F., Urien, S., Albengres, E., Duche, J.C., Tillement, J.: Drug binding in plasma. A summary of recent trends in the study of drug and hormone binding. Clin. Pharmacokinet. 26, 44–58 (1994)

    Article  CAS  Google Scholar 

  22. Chamani, J., Asoodeh, A., Homayoni-Tabrizi, M., Tehranizadeh, Z.A., Baratian, A., Saberi, M.R., Gharanfoli, M.: Spectroscopic and nano-molecular modeling investigation on the binary and ternary bindings of colchicine and lomefloxacin to Human serum albumin with the viewpoint of multi-drug therapy. J. Luminesc. 130, 2476–2486 (2010)

    Article  CAS  Google Scholar 

  23. Tang, J.-H., Luan, F., Chen, X.-G.: Binding analysis of glycyrrhetinic acid to human serum albumin: fluorescence spectroscopy, FTIR, and molecular modeling. Bioorgan. Med. Chem. 14, 3210–3217 (2006)

    Article  CAS  Google Scholar 

  24. He, L.-L., Wang, X., Liu, B., Wang, J., Sun, Y.-G.: Interaction between ranitidine hydrochloride and bovine serum albumin in aqueous solution. J. Solution Chem. 39, 654–664 (2010)

    Google Scholar 

  25. Kathiravan, A., Chandramohan, M., Renganathan, R., Sekar, S.: Spectroscopic studies on the interaction between phycocyanin and bovine serum albumin. J. Mole. Struc. 919, 210–214 (2009)

    Article  CAS  Google Scholar 

  26. Nanda, R.K., Sarkar, N., Banerjee, R.: Probing the interaction of ellagic acid with human serum albumin: a fluorescence spectroscopic study. J. Photochem. Photobiol. A 192, 152–158 (2007)

    Article  CAS  Google Scholar 

  27. Dong, A.C., Huang, P., Caughey, W.S.: Protein secondary structure in water from second-derivative amide I infrared spectra. Biochemistry 29, 3303–3306 (1990)

    Article  CAS  Google Scholar 

  28. Petitpas, I., Bhattacharya, A.A., Twine, S., East, M., Curry, S.: Crystal structure analysis of warfarin binding to human serum albumin. J. Biol. Chem. 276, 22804–22809 (2001)

    Article  CAS  Google Scholar 

  29. Sułkowska, A.: Interaction of drugs with bovine and human serum albumin. J. Mol. Struct. 614, 227–232 (2002)

    Article  Google Scholar 

  30. Trynda-Lemiesz, L., Keppler, B.K., Koztowski, H.: Studies on the interactions between human serum albumin and imidazolium [transtetrachlorobis (imidazol) ruthenate (III)]. J. Inorg. Biochem. 73, 123–128 (1999)

    Article  CAS  Google Scholar 

  31. Xu J.-G., Wang Z.-B.: Methods of Florescence Analysis (3rd ed.). pp. 64–81. Science Press, Beijing (2006)

  32. Lakowicz J. R.: Principles of Fluorescence Spectroscopy (3rd ed.). pp. 277–290. Springer, Heidelberg (2006)

  33. Scatchard, G.: The attractions of protein for small molecules and ions. Ann. N Y Acad. Sci. 51, 660–672 (1949)

    Article  CAS  Google Scholar 

  34. Leckband, D.: Measuring the forces that control protein interactions. Annu. Rev. Biophys. Bimol. Struct. 29, 1–26 (2000)

    Article  CAS  Google Scholar 

  35. Ross, P.D., Subramanian, S.: Thermodynamics of protein association reactions: forces contributing to stability. Biochemistry 20, 3096–3102 (1981)

    Article  CAS  Google Scholar 

  36. Neméthy, G., Scheraga, H.A.: The structure of water and hydrophobic bonding in protein (III). The thermodynamic properties of hydrophobic bonds in proteins. J. Phys. Chem. 66, 1773–1789 (1962)

    Article  Google Scholar 

  37. Sirotkin, V.A., Zinatullin, A.N., Solomonov, B.N., Faizullin, D.A., Fedotov, V.D.: Calorimetric and Fourier transform infrared spectroscopic study of solid proteins immersed in low water organic solvents. Biochim. Biophys. Acta 1547, 359–369 (2001)

    Article  CAS  Google Scholar 

  38. Liu, Y., Xie, M.-X., Kang, J., Zheng, D.: Studies on the interaction of total saponins of Panax notoginseng and human serum albumin by Fourier transform infrared spectroscopy. Spectrochim Acta A 59, 2747–2758 (2003)

    Article  Google Scholar 

  39. Rahmelow, K., Hubner, W.: Secondary structure determination of proteins in aqueous solution by infrared spectroscopy. A comparison of multivariate data analysis. Anal. Biochem. 241, 5–11 (1996)

    Article  CAS  Google Scholar 

  40. Bourassa, P., Dubeau, S., Maharvi, G.M., Fauq, A.H., Thomas, T.J., Tajmir-Riahi, H.A.: Binding of antitumor tamoxifen and its metabolites 4-hydroxytamoxifen and endoxifen to human serum albumin. Biochimie 93, 1089–1101 (2011)

    Article  CAS  Google Scholar 

  41. Bourassa, P., Hasni, I., Tajmir-Riahi, H.A.: Folic acid complexes with human and bovine serum albumins. Food Chem. 129, 1148–1155 (2011)

    Article  CAS  Google Scholar 

  42. Jiang, M., Xie, M.-X., Zheng, D., Liu, Y., Li, X.-Y., Chen, X.: Spectroscopic studies on the interaction of cinnamic acid and its hydroxyl derivatives with human serum albumin. J. Mol. Struct. 692, 71–80 (2004)

    Article  Google Scholar 

  43. Sjoholm, I., Ekman, B., Kober, A., Ljungstedt-Pahlman, I., Seiving, B., Sjodin, T.: Binding of drugs to human serum albumin: XI. The specificity of three binding sites as studied with albumin immobilized in microparticles. Mol. Pharmacol. 16, 767–777 (1979)

    CAS  Google Scholar 

  44. He, J.X., Carter, D.C.: Atomic structure and chemistry of human serum albumin. Nature 358, 209–215 (1992)

    Article  CAS  Google Scholar 

  45. Curry, S., Mandelkow, H., Brick, P., Franks, N.: Crystal structure of human serum albumin complexed with fatty acid reveals an asymmetric distribution of binding sites. Nat. Struct. Biol. 5, 827–835 (1998)

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jiang-Hong Tang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tang, JH., Liang, GB., Zheng, CZ. et al. Investigation on the Binding Behavior of Ellagic Acid to Human Serum Albumin in Aqueous Solution. J Solution Chem 42, 226–238 (2013). https://doi.org/10.1007/s10953-012-9938-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10953-012-9938-9

Keywords

Navigation