Skip to main content
SpringerLink
Log in

Antibacterial and antioxidant properties of hesperidin:β-cyclodextrin complexes obtained by different techniques

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

Abstract

The purpose of this study was to investigate the influence of β-cyclodextrin on aqueous solubility of hesperidin. The inclusion complexes were prepared by different methods (kneading, co-evaporation and lyophilization) and were tested for their antimicrobial and antioxidant activities. Solubility diagrams were drawn at four temperatures (20, 25, 37 and 40 °C) and the corresponding stability constants were calculated. The solubility diagrams obtained were of AL type and the stoichiometric ratio was 1:1. Moreover, the thermodynamic parameters of the complexation reaction were calculated: Gibbs free energy change, free energy change, enthalpy change and entropy change. The results showed that the complexation reaction is more effective with the increase in temperature and in cyclodextrin concentration. The inclusion process is endothermic and spontaneous and the interactions between hesperidin and β-cyclodextrin are hydrophobic. UV–Vis, FTIR, 1HNMR, methods provided valuable information about complex formation. Antibacterial activity was investigated by the agar diffusion method, against Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922 and Candida albicans ATCC 10231. The results revealed that all the prepared compounds display a higher antibacterial activity compared to hesperidin. Also, the inclusion compounds presented an improved antioxidant activity, demonstrated by the determination of inhibition of lipoxygenase activity, DPPH radical scavenging activity and determination of reducing capacity. In vitro dissolution tests demonstrated that the inclusion compounds have an improved dissolution, compared to free hesperidin. The enhancement in the solubility, antibacterial and antioxidant activities depend on the method of preparation.

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
Fig. 11
Fig. 12

Similar content being viewed by others

References

  1. Tong, N., Zhang, Z., Zhang, W., Qiu, Y., Gong, Y., Yin, L., Qiu, Q., Wu, X.: Diosmin alleviates retinal edema by protecting the blood-retinal barrier and reducing retinal vascular permeability during ischemia/reperfusion injury. PLos One 8, 1–10 (2013)

    Google Scholar 

  2. Sezer, A., Usta, U., Kocak, Z., Yagci, M.A.: The effect of a flavonoid fractions diosmin + hesperidin on radiation-induced acute proctitis in a rat model. J. Cancer Res. Ther. 7, 152–156 (2011)

    Article  CAS  Google Scholar 

  3. Lee, C.J., Wilson, L., Jordan, M.A., Nguyen, V., Tang, J., Smiyun, G.: Hesperidin suppressed proliferations of both human breast cancer and androgen-dependent prostate cancer cells. Phytother. Res. 24, 15–19 (2010)

    Article  Google Scholar 

  4. Monforte, M.T., Trovato, A., Kirjavainen, S., Forestieri, A.M., Galati, E.M., Lo Curto, R.B.: Biological effects of hesperidin, a Citrus flavonoid. (note II): hypolipidemic activity on experimental hypercholesterolemia in rat. Farmaco 50, 595–599 (1995)

    CAS  Google Scholar 

  5. Chiba, H., Uehara, M., Wu, J., Wang, X., Masuyama, R., Suzuki, K., Kanazawa, K., Ishimi, Y.: Hesperidin, a citrus flavonoid, inhibits bone loss and decreases serum and hepatic lipids in ovariectomized mice. J. Nutr. 133, 1892–1897 (2003)

    CAS  Google Scholar 

  6. Loscalzo, L.M., Wasowski, C., Paladini, A.C., Marder, M.: Opioid receptors are involved in the sedative and antinociceptive effects of hesperidin as well as in its potentiation with benzodiazepines. Eur. J. Pharmacol. 580, 306–313 (2008)

    Article  CAS  Google Scholar 

  7. Brewster, M.E., Loftsson, T.: Cyclodextrins as pharmaceutical solubilizers. Adv. Drug Deliv. Rev. 59, 645–666 (2007)

    Article  CAS  Google Scholar 

  8. Arun, R., Ashok, K.C.K., Sravanthi, V.V.N.S.S.: Cyclodextrins as drug carrier molecule: a review. Sci. Pharm. 76, 567–598 (2008)

    Article  Google Scholar 

  9. Davis, M.E., Brewster, M.E.: Cyclodextrin-based pharmaceutics: past, present and future. Nat. Rev. Drug Discov. 3, 1023–1035 (2004)

    Article  CAS  Google Scholar 

  10. Loftsson, T., Brewster, M.E.: Pharmaceutical applications of cyclodextrins: basic science and product development. J. Pharm. Pharmacol. 62, 1607–1621 (2010)

    Article  CAS  Google Scholar 

  11. Spulber, M., Pinteala, M., Fifere, A., Moldoveanu, C., Mangalagiu, I., Harabagiu, V., Simionescu, B.C.: Water soluble complexes of methyl-beta-cyclodextrin and sulconazole nitrate. J. Incl. Phenom. Macrocycl. Chem. 62, 135–142 (2008)

    Article  CAS  Google Scholar 

  12. Challa, R., Ahuja, A., Ali, J., Khar, R.K.: Cyclodextrins in drug delivery: an updated review. AAPS Pharm. Sci. Tech. 6, 329–357 (2005)

    Article  Google Scholar 

  13. Higuchi, T., Connors, K.A.: Phase-solubility techniques. Adv. Anal. Chem. Instrum. 4, 117–122 (1965)

    CAS  Google Scholar 

  14. Domańska, U., Pelczarska, A., Pobudkowska, A.: Effect of 2-hydroxypropyl-β-cyclodextrin on solubility of sparingly soluble drug derivatives of anthranilic acid. Int. J. Mol. Sci. 12, 2383–2394 (2011)

    Article  Google Scholar 

  15. Lv, H.X., Zhang, Z.H., Jiang, H., Waddad, A.Y., Zhou, J.P.: Preparation, physicochemical characteristics and bioavailability studies of an atorvastatin hydroxypropyl-β-cyclodextrin complex. Pharmazie 67, 46–53 (2012)

    CAS  Google Scholar 

  16. Hadžiabetdić, J., Elezović, A., Rahić, O., Mujezin, I.: Effect of cyclodextrin complexation on the aqueous solubility of diazepam and nitrazepam: phase-solubility analysis, thermodynamic properties. Am. J. Anal. Chem. 3, 811–819 (2012)

    Article  Google Scholar 

  17. Batt, D.K., Garala, K.C.: Preparation and evaluation of inclusion complexes of diacerein with β-cyclodextrin and hydroxypropyl β-cyclodextrin. J. Incl. Phenom. Macrocycl. Chem. 77, 471–481 (2013)

    Article  CAS  Google Scholar 

  18. George, S.J., Vasudevan, D.T.: Studies on preparation, characterization and solubility of 2-HP-beta-cyclodextrin-meclizine HCl inclusion complexes. Pharmaceutics 4, 220–227 (2012)

    CAS  Google Scholar 

  19. Salústio, P.J., Feio, G., Figueirinhas, J.L., Pinto, J.F., Cabral Marques, H.M.: The influence of the preparation methods on the inclusion of model drugs in a beta-cyclodextrin cavity. Eur. J. Pharm. Biopharm. 71, 377–386 (2009)

    Article  Google Scholar 

  20. Patel, R., Patel, M.: Solid-state characterization and in vitro dissolution behavior of lorazepam: hydroxypropyl-β-cyclodextrin inclusion complex. Drug Discov. Ther. 4, 442–452 (2010)

    CAS  Google Scholar 

  21. Petralito, S., Zanardi, I., Memoli, A., Annesini, M.C., Travagli, V.: Solubility, spectroscopic properties and photostability of rhein/cyclodextrin inclusion complex. Spectrochim. Acta. A. 74, 1254–1259 (2009)

    Article  Google Scholar 

  22. Dani, R.M.A.M., Elbashir, A.A.: Host-guest inclusion complex of β-cyclodextrin and cephalexin and its analytical application. Int. J. Pharm. Chem. Res. 2, 1–13 (2013)

    Article  Google Scholar 

  23. Marangoci, N., Mares, M., Silion, M., Fifere, A., Varganici, C., Nicolescu, A., Deleanu, C., Coroaba, A., Pinteala, M., Simionescu, B.C.: Inclusion complex of a new propiconazole derivative with beta-cyclodextrin: NMR, ESI-MS and preliminary pharmacological studies. Results Pharma. Sci. 1, 27–37 (2011)

    Article  CAS  Google Scholar 

  24. Cui, L., Zhang, Z.H., Sun, E., Jia, X.B.: Effect of beta-cyclodextrin complexation on solubility and enzymatic conversion of naringin. Int. J. Mol. Sci. 13, 14251–14261 (2012)

    Article  CAS  Google Scholar 

  25. Valnet, J., Duraffourd, C., Duraffourd, P., Lapraz, J.C.: L’aromatogramme: nouveaux resultats et essai d’interpretation sur 268 cas cliniques. Plant Médicin. Phytothér. 12, 43–52 (1978)

    Google Scholar 

  26. Danciu, C., Soica, C., Oltean, M., Avram, S., Borcan, F., Csanyi, E., Ambrus, R., Zupko, I., Muntean, D., Dehelean, C.A., Craina, M., Popovici, R.A.: Genistein in 1:1 inclusion complexes with ramified cyclodextrins: theoretical, physicochemical and biological evaluation. Int. J. Mol. Sci. 15, 1962–1982 (2014)

    Article  Google Scholar 

  27. Malterud, K.E., Rydland, K.M.: Inhibitors of 15-lipoxygenase from orange peel. J. Agric. Food Chem. 48, 5576–5580 (2000)

    Article  CAS  Google Scholar 

  28. Hatano, T., Kagawa, H., Yasuhara, T., Okuda, T.: Two new flavonoids and other constituents in licorice root: their relative astringency and radical scavenging effects. Chem. Pharm. Bull 36, 2090–2097 (1988)

    Article  CAS  Google Scholar 

  29. 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 

  30. Oyazu, M.: Studies on products of browning reactions: antioxidative activities of products of browning reaction prepared from glucosamine. Jpn. J. Nutr. 44, 307–315 (1986)

    Article  Google Scholar 

  31. Samal, H.B., Debata, J., Kumar, N.N., Sneha, S., Patra, P.K.: Solubility and dissolution improvement of aceclofenac using β-Cyclodextrin. Int. J. Drug Dev. Res. 4, 326–333 (2012)

    CAS  Google Scholar 

  32. Dua, K., Pabreja, K., Ramana, M.V., Lather, V.: Dissolution behavior of β-cyclodextrin molecular inclusion complexes of aceclofenac. J. Pharm. Bioallied Sci. 3, 417–425 (2011)

    Article  CAS  Google Scholar 

  33. Calabro, M.L., Tommasini, S., Donato, P., Stancanelli, R., Raneri, D., Catania, S., Costa, C., Villari, V., Ficarra, P., Ficarra, R.: The rutin/β-cyclodextrin interactions in fully aqueous solution: spectroscopic studies and biological assays. J. Pharm. Biomed. Anal. 36, 1019–1027 (2005)

    Article  CAS  Google Scholar 

  34. Markham, K.R.: Techniques of flavonoid identification. Academic Press, New York (1982)

    Google Scholar 

  35. Connors, K.A.: Thermodynamics of pharmaceutical systems: an introduction for students of pharmacy. John Wiley & Sons Inc, Hoboken, New Jersey (2002)

    Book  Google Scholar 

  36. Liu, B., Li, W., Nguyen, T.A., Zhao, J.: Empirical, thermodynamic and quantum-chemical investigations of inclusion complexation between flavanones and (2-hydroxypropyl)-cyclodextrins. Food Chem. 134, 926–932 (2012)

    Article  CAS  Google Scholar 

  37. Bloch, D.W., Elegakey, M.A., Speiser, P.P.: Solid dispersion of chlorthalidone in urea phase diagram and dissolution characteristics. Pharm. Acta Helv. 57, 231–235 (1982)

    CAS  Google Scholar 

  38. Guo, X., Shuang, S., Wang, X., Dong, C., Pan, J., Aboul-Enein, H.Y.: Comparative study on the inclusion behaviour of cyclodextrin derivatives with venoruton and rutin by thin layer chromatography. Biomed. Chromatogr. 18, 559–563 (2004)

    Article  CAS  Google Scholar 

  39. Roik, N.V., Belyakova, L.A.: Thermodynamic, IR spectral and X-ray diffraction studies of the β-cyclodextrin-para-aminobenzoic acid inclusion complex. J. Incl. Phenom. Macrocycl. Chem. 69, 315–319 (2011)

    Article  CAS  Google Scholar 

  40. Lin, S.Y., Lin, H.L., Lin, C.C., Hsu, C.H., Wu T.K., Huang Y.T.: Thermodynamic study of grinding-induced loratadine inclusion complex formation using thermal analysis and curve-fitted FTIR determination. In: Moreno-Piraján, J.C. (ed.) Thermodynamics - Physical Chemistry of Aqueous Systems (2011). doi: 10.5772/21338

  41. Şamli, M., Korel, F., Bayraktar, O.: Characterization of silk fibroin based films loaded with rutin–β-cyclodextrin inclusion complexes. J. Incl. Phenom. Macrocycl. Chem. (2014). doi:10.1007/s10847-014-0396-4

    Google Scholar 

  42. Miron, L., Mares, M., Nastasa, V., Spulber, M., Fifere, A., Pinteala, M., Harabagiu, V., Simionescu, B.C.: Water soluble sulconazole-β-cyclodextrin complex: physico-chemical characterization and preliminary pharmacological studies. J. Incl. Phenom. Macrocycl. Chem. 63, 159–162 (2009)

    Article  CAS  Google Scholar 

  43. Fatiha, M., Khatmi, D.E., Largate, L.: Theoretical approach in the study of the inclusion processes of sulconazole with β-cyclodextrin. J. Mol. Liq. 154, 1–5 (2010)

    Article  CAS  Google Scholar 

  44. Piel, G., Dive, G., Ervard, B., Van Hees, T., Henry de Hassonville, S., Delattre, L.: Molecular modeling study of β- and γ-cyclodextrin complexes with miconazole. Eur. J. Pharm. Sci. 13, 271–279 (2001)

    Article  CAS  Google Scholar 

  45. Grandelli, H.E., Stickle, B., Whittington, A., Kiran, E.: Inclusion complex formation of β-cyclodextrin and naproxen: a study on exothermic complex formation by differential scanning calorimetry. Incl. Phenom. Macrocycl. Chem. 77, 269–277 (2013)

    Article  CAS  Google Scholar 

  46. Panda, S., Singh, D.L.: Study of antioxidant, antimicrobial and anthelmintic properties of 1-nicotinoyl-4-aryl-3-methyl 3a,4-dihydropyrazolo [3,4c] pyrazoles and their inclusion complexes with β-cyclodextrin. World J. Pharm. Pharm. Sci. 3, 1639–1654 (2014)

    CAS  Google Scholar 

  47. Stavniichuk, R., Drel, V.R., Shevalye, H., Vareniuk, I., Stevens, M.J., Nadler, J.L., Obrosova, I.G.: Role of 12/15-lipoxygenase in nitrosative stress and peripheral prediabetic and diabetic neuropathies. Free Radicals Biol. Med. 49, 1036–1045 (2010)

    Article  CAS  Google Scholar 

  48. Wittwer, J., Hersberger, M.: The two faces of the 15-lipoxygenase in atherosclerosis. Prostaglandins Leukot. Essent. Fatty Acids 77, 67–77 (2007)

    Article  CAS  Google Scholar 

  49. Yang, H., Zhuo, J.M., Chu, J., Chinnici, C., Praticò, D.: Amelioration of the Alzheimer’s disease phenotype by absence of 12/15-Lipoxygenase. Biol. Psychiatry 68, 922–929 (2010)

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Scientific research funded by the University of Medicine and Pharmacy “Grigore T. Popa” Iasi, based on the contract no. 4872/18.03.2013 and the PN-II-ID-PCCE-2011-2-0028 Grant.

Author information

Authors and Affiliations

  1. “Grigore T. Popa” University of Medicine and Pharmacy Iasi, Iasi, Romania

    Andreia Corciova, Constantin Ciobanu, Antonia Poiata, Cornelia Mircea & Tudor Pinteala

  2. “Petru Poni” Institute of Macromolecular Chemistry, 41A Grigore Ghica-Voda Alley, 700487, Iasi, Romania

    Alina Nicolescu, Mioara Drobota, Cristian-Dragos Varganici & Narcisa Marangoci

Authors
  1. Andreia Corciova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Constantin Ciobanu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Antonia Poiata
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cornelia Mircea
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alina Nicolescu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mioara Drobota
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Cristian-Dragos Varganici
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tudor Pinteala
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Narcisa Marangoci
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Narcisa Marangoci.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Corciova, A., Ciobanu, C., Poiata, A. et al. Antibacterial and antioxidant properties of hesperidin:β-cyclodextrin complexes obtained by different techniques. J Incl Phenom Macrocycl Chem 81, 71–84 (2015). https://doi.org/10.1007/s10847-014-0434-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10847-014-0434-2

Keywords

Search

Navigation