Skip to main content
SpringerLink
Log in

On the complexation of quercetin with methyl-β-cyclodextrin: photostability and antioxidant studies

  • Original Article
  • Published:
Journal of Inclusion Phenomena and Macrocyclic Chemistry Aims and scope Submit manuscript

Abstract

Quercetin, a plant-derived flavonoid, has been extensively investigated for a wide range of potential health benefits linked to its antioxidant properties. Unfortunately the topical administration of this molecule is restricted by its fast photodegradation. In the attempt to overcome this limitation the inclusion complex between quercetin (Q) and methyl-β-cyclodextrin (Me-β-CD) was prepared and previously investigated by a molecular modelling study, a solubility diagram and a DSC analysis. Successively the kinetics of photodegradation, the antiradical, metal chelating and anti-lipoperoxidative activities were studied by comparing the complex with free Q. In addition the accumulation of Q in porcine skin was evaluated after in vitro topical application by means of vertical Franz cells. The complex formation resulted useful in enhancing the solubility of Q without significantly reducing its antioxidant ability. A modest improvement in the photostability was also observed.

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
Fig. 10

Similar content being viewed by others

References

  1. Halliwell, B., Gutteridge, J.M.: Free radicals, ageing and disease. In: Free Radicals in Biology and Medicine. 2nd edn, pp. 446–493. Clarendon Press, Oxford University Press (1989)

  2. Korkina, L.G., Afanas’ev, I.B.: Antioxidant and chelating properties flavonoids. Adv. Pharmacol. 38, 151–163 (1997)

    Article  CAS  Google Scholar 

  3. Ho, C.T., Chen, Q., Shi, H., Zhang, K.Q., Rosen, R.T.: Antioxidative effect of polyphenol extract prepared from various Chinese teas. Prev. Med. 21, 520–525 (1992)

    Article  CAS  Google Scholar 

  4. van het Hof, K.H., Wiseman, S.A., Yang, C.S., Tijburg, L.B.M.: Plasma and lipoprotein of tea catechins following repeated tea consumption. Proc. Soc. Exp. Biol. Med. 220, 203–209 (1999)

    Article  Google Scholar 

  5. Pietta, P.G.: Flavonoids as antioxidants. J. Nat. Prod. 63, 1035–1042 (2000)

    Article  CAS  Google Scholar 

  6. Beret, A., Cazenave, J.P.: The effect of flavonoids on blood–vessel wall interactions. In: Cody, V., Middleton, E., Harborne, J.B., Beretz, A. (eds.) Plant Flavonoids in Biology and Medicine II: Biochemical, Cellular and Medicinal Properties, pp. 187–200. Alan R. Liss. Inc., New York (1988)

    Google Scholar 

  7. Manthey, J.A., Guthrie, N., Grohmann, R.: Biological properties of citrus flavonoids pertaining to cancer and inflammation. Curr. Med. Chem. 8, 133–153 (2001)

    Google Scholar 

  8. Ohshima, H., Yoshie, Y., Auriol, S., Gilibert, I.: Antioxidant and pro-oxidant actions of flavonoids: effect on DNA (peroxynitrite and nitroxyl anion). Free Radic. Biol. Med. 25, 1057–1065 (1998)

    Article  CAS  Google Scholar 

  9. Aviram, M., Fuhrman, B.: Effects of flavonoids on the oxidation of low-density lipoprotein and atherosclerosis. In: Rice-Evans, C.A., Packer, L. (eds.) Flavonoids in Health and Disease, 2nd edn. Revised and Expanded, pp. 165–203. Marcel Dekker Inc., New York (1998)

    Google Scholar 

  10. Kandaswami, C., Middleton, E.: Flavonoids as antioxidants. In: Shahidi, F. (ed.) Natural Antioxidant Chemistry Health Effects and Practical Applications, pp. 174–194. AOCS Press, Champaign, IL (1997)

    Google Scholar 

  11. Rice-Evans, C.A., Miller, N.J., Paganga, G.: Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic. Biol. Med. 20(7), 933–956 (1996)

    Article  CAS  Google Scholar 

  12. Sahu, S.C., Green, S.: Food antioxidants: their dual role in carcinogenesis. In: Baskin, S., Salem, H. (eds.) Oxidants, Antioxidant and Free Radicals, pp. 328–330. Taylor and Francis, Washington (1997)

    Google Scholar 

  13. Afanos’ev, B., Dorozhko, A.I., Brodskii, A.V., Kostyuk, A., Potapovitech, A.I.: Chelating and free scavenging mechanism of inhibitory action of rutin and quercetin in lipid peroxidation. Biochem. Pharmacol. 38, 1763–1769 (1989)

    Article  Google Scholar 

  14. Potapovich, A.I., Kostyuk, V.A.: Comparative study of antioxidant properties of cytoprotective activity of flavonoids. Biochemistry (Mosc.) 68, 514–519 (2003)

    Article  CAS  Google Scholar 

  15. Tsimogiannis, D.I., Oreopoulou, V.: Free radical scavenging and antioxidant activity of 5,7,3′,4′-hydroxy-substituted flavonoids. IFSET 5, 523–528 (2004)

    CAS  Google Scholar 

  16. Jovanovic, S.V., Steenken, S., Hara, Y., Simic, M.G.: Reduction potentials of flavonoids and model phenoxyl radicals which ring in flavonoids is responsible for antioxidant activity? J. Chem. Soc. Perkin Trans. 2, 2497–2504 (1996)

    Google Scholar 

  17. Hendricks, S.B., Borthwick, H.A.: The physiological functions of phytochrome. In: Goodwin, T.W. (ed.) Chemistry and Biochemistry of Plant Pigments, pp. 405–436. Academic Press, London (1965)

    Google Scholar 

  18. Coohill, T.P.: Action spectroscopy: ultraviolet radiation. In: Horspool, W.M., Song, P.S. (eds.) CRC Handbook of Organic Photochemistry and Photobiology, pp. 1267–1275. CRC Press, Boca Raton (1995)

    Google Scholar 

  19. Bouhamidi, R., Prévost, V., Nouvelot, A.: High protection by grape seed proanthocyanidins (GSPC) of polyunsaturated fatty acids against UV-C induced peroxidation. Life Sci. 321, 31–38 (1998)

    CAS  Google Scholar 

  20. Greenspan, H.C., Aruoma, O.I.: Oxidative stress and apoptosis in HIV infection: a role for plant-derived metabolites with synergistic antioxidant activity. Immunol. Today 15, 209–213 (1994)

    Article  CAS  Google Scholar 

  21. Yuting, C., Rongliang, Z., Zhongjian, J., Yong, J.: Flavonoids as superoxide scavengers and antioxidants. Free Radic. Biol. Med. 9, 19–21 (1990)

    Article  Google Scholar 

  22. Pinelo, M., Manzocco, L., Nunez, M.J., Nicoli, C.: Solvent effect on quercetin antioxidant capacity. Food Chem. 88, 201–207 (2004)

    Article  CAS  Google Scholar 

  23. Nicoli, M.C., Calligaris, S., Manzocco, L.: Effect of enzymatic and chemical oxidation on the antioxidant capacity of catechin model systems and apple derivatives. J. Agric. Food Chem. 48, 4576–4580 (2000)

    Article  CAS  Google Scholar 

  24. Calabrò, M.L., Tommasini, S., Donato, P., Raneri, D., Stancanelli, R., Ficarra, P., Ficarra, R., Costa, C., Catania, S., Rustichelli, C., Gamberini, G.: Effects of α- and β-cyclodextrin complexation on the physico-chemical properties and antioxidant activity of some 3-hydroxyflavones. J. Pharm. Biomed. Anal. 35, 365–377 (2004)

    Article  Google Scholar 

  25. Ficarra, R., Ficarra, P., Tommasini, S., Campagna, S., Guglielmo, O.: Photochemistry of flavonoids solvent effect on photochemical behaviour of 3-hydroxyflavone. Boll. Chim. Farm. 133, 665–669 (1994)

    CAS  Google Scholar 

  26. Falkovskaia, E., Sengupta, P.K., Kasha, M.: Photophysical induction of dual fluorescence of quercetin and related hydroxyflavones upon intermolecular H-bonding to solvent matrix. Chem. Phys. Lett. 297, 109–116 (1998)

    Article  CAS  Google Scholar 

  27. Rezende, B.A., Cortes, S.F., De Sousa, F.B., Lula, I.S., Schmitt, M., Sinisterra, R.D., Lemos, V.S.: Complexation with β-cyclodextrin confers oral activity on the flavonoid dioclein. Int. J. Pharm. 367, 133–139 (2009)

    Article  CAS  Google Scholar 

  28. Alvarez-Parrilla, E., De La Rosa, L.A., Torres-Riva, F., Rodrigo-García, J., González-Aguilar, G.A.: Complexation of apple antioxidants: chlorogenic acid, quercetin and rutin by β-cyclodextrins. J. Incl. Phenom. Macrocycl. Chem. 53, 121–129 (2005)

    Article  CAS  Google Scholar 

  29. Loftsson, T., Brewster, M.E.: Pharmaceutical applications of cyclodextrins. Drug solubilization and stabilization. J. Pharm. Sci. 85, 1017–1025 (1986)

    Article  Google Scholar 

  30. Mielcarek, J.: Photochemical stability of the inclusion complexes formed by modified 1,4-dihydropyridine derivatives with β-cyclodextrin. J. Pharm. Biomed. Anal. 15, 681–686 (1997)

    Article  CAS  Google Scholar 

  31. Sortino, S., Scaiano, J.C., De Guidi, G., Monti, S.: Effect of β-cyclodextrin complexation on the photochemical and photosensitizing properties of tolmetin: a steady state and time resolved study. Photochem. Photobiol. 70, 549–556 (1999)

    CAS  Google Scholar 

  32. Scalia, S., Villani, S., Casolari, A.: Inclusion complexation of the sunscreen agent 2-ethylhexyl-p-dimethylaminobenzoate with hydroxypropyl-β-cyclodextrin: effect on photostability. J. Pharm. Pharmacol. 51, 1367–1374 (1999)

    Article  CAS  Google Scholar 

  33. Albini, A., Fasani, E.: Photochemistry of drugs: an overview and practical problems. In: Albini, A., Fasani, E. (eds.) Drugs: photochemistry and photostability, pp. 1–74. The Royal Society of Chemistry, Cambridge, UK (1998)

    Google Scholar 

  34. Tommasini, S., Calabrò, M.L., Donato, P., Raneri, D., Guglielmo, G., Ficarra, P., Ficarra, R.: Comparative photodegradation studies on 3-hydroxyflavone: influence of different media, pH and light sources. J. Pharm. Biomed. Anal. 35, 389–397 (2004)

    Article  CAS  Google Scholar 

  35. Lucas-Abellán, C., Fortea, I., Gabaldón, J.A., Núñez-Delicado, E.: Encapsulation of quercetin and myricetin in cyclodextrins at acidic pH. J. Agric. Food Chem. 56, 255–259 (2008)

    Article  Google Scholar 

  36. Yu, Z., Cui, M., Yan, C., Song, F., Liu, Z., Liu, S.: Investigation of heptakis (2,6-di-O-methyl)-β-cyclodextrin inclusion complexes with flavonoid glycosides by electrospray ionization mass spectrometry. Rapid Commun. Mass Spectrom. 21, 683–690 (2007)

    Article  CAS  Google Scholar 

  37. Jullian, C., Moyano, L., Yañez, C., Olea-Azar, C.: Complexation of quercetin with three kinds of cyclodextrins: an antioxidant study. Spectrochim. Acta A 67, 230–234 (2007)

    Article  Google Scholar 

  38. Kim, H., Choi, J., Jung, S.: Inclusion complexes of modified cyclodextrins with some flavonols. J. Incl. Phenom. Macrocycl. Chem. 64, 43–47 (2009)

    Article  CAS  Google Scholar 

  39. MOE: version 2008.10, Chemical Computing Group, Montreal, QC, Canada. http://www.chemcomp.com/ (2008)

  40. Sapino, S., Trotta, M., Ermondi, G., Caron, G., Cavalli, R., Carlotti, M.E.: On the complexation of trolox with methyl-β-cyclodextrin: characterization, molecular modelling and photostabilizing properties. J. Incl. Phenom. Macrocycl. Chem. 62, 179–186 (2008)

    Article  CAS  Google Scholar 

  41. Higuchi, T., Connors, A.: Phase solubility techniques. Adv. Anal. Chem. Instrum. 4, 117–212 (1965)

    CAS  Google Scholar 

  42. Brand-Williams, W., Cuvelier, M.E., Berset, C.: Use of a free radical method to evaluate antioxidant activity. Food Sci. Technol. 28, 25–30 (1995)

    CAS  Google Scholar 

  43. Jang, S., Xu, Z.: Lipophilic and hydrophilic antioxidants and their antioxidant activities in purple rice bran. J. Agric. Food Chem. 57, 858–862 (2009)

    Article  CAS  Google Scholar 

  44. Bay, B.-H., Lee, Y.-K., Tan, B.K.-H., Ling, E.-A.: Lipid peroxidative stress and antioxidative enzymes in brains of milk-supplemented rats. Neurosci. Lett. 277, 127–133 (1999)

    Article  CAS  Google Scholar 

  45. Sapino, S., Carlotti, M.E., Caron, G., Ugazio, E., Cavalli, R.: In silico design, photostability and biological properties of the complex resveratrol/hydroxypropyl-β-cyclodextrin. J. Incl. Phenom. Macrocycl. Chem. 63, 171–180 (2009)

    Article  CAS  Google Scholar 

  46. Christoff, M., Toscano, V.G., Baader, W.J.: Influence of methoxy substitution on flavonoid photophysics: a steady state and laser flash photolysis study. J. Photochem. Photobiol. A Chem. 101, 11–20 (1996)

    Article  CAS  Google Scholar 

  47. Smith, G.J., Thomsen, S.J., Markham, K.R., Andary, C., Cardon, D.: The photostabilities of natural occurring 5-hydroxyflavone, flavonols, their glycosides and their aluminium complex. J. Photochem. Photobiol. A Chem. 136, 87–91 (2000)

    Article  CAS  Google Scholar 

  48. Bayomi, M.A., Abanumay, K.A., Al-Angary, A.A.: Effect of inclusion complexation with cyclodextrins on photostability of nifedipine in solid state. Int. J. Pharm. 243, 107–117 (2002)

    Article  CAS  Google Scholar 

  49. Godwin, D.A., Wiley, C.J., Felton, L.A.: Using cyclodextrin complexation to enhance secondary photoprotection of topically applied ibuprofen. Eur. J. Pharm. Biopharm. 62, 85–93 (2006)

    Article  CAS  Google Scholar 

  50. Carlotti, M.E., Sapino, S., Vione, D., Pelizzetti, E., Trotta, M.: Photostability of trolox in water/ethanol, water and Oramix CG110, in the absence and in the presence of TiO2. J. Dispers. Sci. Technol. 25, 193–207 (2004)

    Article  CAS  Google Scholar 

  51. Carlotti, M.E., Sapino, S., Vione, D., Minero, C., Peira, E., Trotta, M.: Study on the photodegradation of salicylic acid in different vehicles in the absence and in the presence of TiO2. J. Dispers. Sci. Technol. 28, 805–818 (2007)

    Article  CAS  Google Scholar 

  52. Murias, M., Jäger, W., Handler, N., Erker, T., Horvath, Z., Szekeres, T., Nohl, H., Gille, L.: Antioxidant, prooxidant and cytotoxic activity of hydroxylated resveratrol analogues: structure–activity relationship. Biochem. Pharmacol. 69, 903–912 (1995)

    Article  Google Scholar 

  53. Goldstein, S., Meyerstein, D., Czapski, G.: The Fenton reagents. Free Radic. Biol. Med. 15, 435–445 (1993)

    Article  CAS  Google Scholar 

  54. Gülçin, I.: Antioxidant activity of caffeic acid (3,4-dihydroxycinnamic acid). Toxicology 217, 213–220 (2006)

    Article  Google Scholar 

  55. Diembeck, W., Beck, H., Benech-Kieffer, F., Courtellemont, P., Dupuis, J., Lowell, W., Paye, M., Spengler, M., Steiling, W.: Test guidelines for in vitro assessment of dermal absorption and percutaneous penetration of cosmetic ingredients. Food Chem. Toxicol. 37, 191–205 (1999)

    Article  CAS  Google Scholar 

  56. Loftsson, T., Stefánsson, E.: Effect of cyclodextrins on topical drug delivery to the eye. Drug Dev. Ind. Pharm. 23, 473–481 (1997)

    Article  CAS  Google Scholar 

  57. Carlotti, M.E., Ugazio, E., Gastaldi, L., Sapino, S., Vione, D., Fenoglio, I., Fubini, B.: Specific effects of single antioxidants in the lipid peroxidation caused by nano-titania used in sunscreen lotions. J. Photochem. Photobiol. B Biol. 96, 130–135 (2009)

    Article  CAS  Google Scholar 

  58. Carlotti, M.E., Ugazio, E., Sapino, S., Fenoglio, I., Greco, G., Fubini, B.: Role of particle coating in controlling skin damage photoinduced by titania nanoparticles. Free Radic. Res. 43, 312–322 (2009)

    Article  CAS  Google Scholar 

  59. Jacobi, U., Kaiser, M., Toll, R., Mangelsdorf, S., Audring, H., Otberg, N., Sterry, W., Lademann, J.: Porcine ear skin: an in vitro model for human skin. Skin Res. Technol. 13, 19–24 (2007)

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, via P. Giuria 9, 10125, Turin, Italy

    M. E. Carlotti, S. Sapino, E. Ugazio & G. Caron

Authors
  1. M. E. Carlotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Sapino
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. Ugazio
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. Caron
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. E. Carlotti.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Carlotti, M.E., Sapino, S., Ugazio, E. et al. On the complexation of quercetin with methyl-β-cyclodextrin: photostability and antioxidant studies. J Incl Phenom Macrocycl Chem 70, 81–90 (2011). https://doi.org/10.1007/s10847-010-9864-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10847-010-9864-7

Keywords

Search

Navigation