Dimitrios A Diamantis1, Sarka Ramesova2, Christos M Chatzigiannis1, Ilaria Degano3, Paraskevi S Gerogianni4, Konstantina E Karadima5, Sonia Perikleous5, Dimitrios Rekkas5, Ioannis P Gerothanassis1, Dimitrios Galaris4, Thomas Mavromoustakos6, Georgia Valsami5, Romana Sokolova7, Andreas G Tzakos8. 1. Department of Chemistry, Section of Organic Chemistry and Biochemistry, University of Ioannina, Ioannina 45110, Greece. 2. J. Heyrovský Institute of Physical Chemistry of the Czech Academy of Sciences, Dolejškova 3, 18223 Prague, Czech Republic. 3. Department of Chemistry and Industrial Chemistry, University of Pisa, Via Moruzzi 13, 56124 Pisa, Italy. 4. Laboratory of Biological Chemistry, University of Ioannina, School of Health Sciences, Faculty of Medicine, 451 10 Ioannina, Greece. 5. Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis Zografou 15771, Greece. 6. Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou 15771, Greece. 7. J. Heyrovský Institute of Physical Chemistry of the Czech Academy of Sciences, Dolejškova 3, 18223 Prague, Czech Republic. Electronic address: romana.sokolova@jh-inst.cas.cz. 8. Department of Chemistry, Section of Organic Chemistry and Biochemistry, University of Ioannina, Ioannina 45110, Greece. Electronic address: agtzakos@gmail.com.
Abstract
BACKGROUND: Flavonoids possess a rich polypharmacological profile and their biological role is linked to their oxidation state protecting DNA from oxidative stress damage. However, their bioavailability is hampered due to their poor aqueous solubility. This can be surpassed through encapsulation to supramolecular carriers as cyclodextrin (CD). A quercetin- 2HP-β-CD complex has been formerly reported by us. However, once the flavonoid is in its 2HP-β-CD encapsulated state its oxidation potential, its decomplexation mechanism, its potential to protect DNA damage from oxidative stress remained elusive. To unveil this, an array of biophysical techniques was used. METHODS: The quercetin-2HP-β-CD complex was evaluated through solubility and dissolution experiments, electrochemical and spectroelectrochemical studies (Cyclic Voltammetry), UV-Vis spectroscopy, HPLC-ESI-MS/MS and HPLC-DAD, fluorescence spectroscopy, NMR Spectroscopy, theoretical calculations (density functional theory (DFT)) and biological evaluation of the protection offered against H2O2-induced DNA damage. RESULTS: Encapsulation of quercetin inside the supramolecule's cavity enhanced its solubility and retained its oxidation profile. Although the protective ability of the quercetin-2HP-β-CD complex against H2O2 was diminished, iron serves as a chemical stimulus to dissociate the complex and release quercetin. CONCLUSIONS: We found that in a quercetin-2HP-β-CD inclusion complex quercetin retains its oxidation profile similarly to its native state, while iron can operate as a chemical stimulus to release quercetin from its host cavity. GENERAL SIGNIFICANCE: The oxidation profile of a natural product once it is encapsulated in a supramolecular carrier was unveiled as also it was discovered that decomplexation can be triggered by a chemical stimilus.
BACKGROUND:Flavonoids possess a rich polypharmacological profile and their biological role is linked to their oxidation state protecting DNA from oxidative stress damage. However, their bioavailability is hampered due to their poor aqueous solubility. This can be surpassed through encapsulation to supramolecular carriers as cyclodextrin (CD). A quercetin- 2HP-β-CD complex has been formerly reported by us. However, once the flavonoid is in its 2HP-β-CD encapsulated state its oxidation potential, its decomplexation mechanism, its potential to protect DNA damage from oxidative stress remained elusive. To unveil this, an array of biophysical techniques was used. METHODS: The quercetin-2HP-β-CD complex was evaluated through solubility and dissolution experiments, electrochemical and spectroelectrochemical studies (Cyclic Voltammetry), UV-Vis spectroscopy, HPLC-ESI-MS/MS and HPLC-DAD, fluorescence spectroscopy, NMR Spectroscopy, theoretical calculations (density functional theory (DFT)) and biological evaluation of the protection offered against H2O2-induced DNA damage. RESULTS: Encapsulation of quercetin inside the supramolecule's cavity enhanced its solubility and retained its oxidation profile. Although the protective ability of the quercetin-2HP-β-CD complex against H2O2 was diminished, iron serves as a chemical stimulus to dissociate the complex and release quercetin. CONCLUSIONS: We found that in a quercetin-2HP-β-CD inclusion complex quercetin retains its oxidation profile similarly to its native state, while iron can operate as a chemical stimulus to release quercetin from its host cavity. GENERAL SIGNIFICANCE: The oxidation profile of a natural product once it is encapsulated in a supramolecular carrier was unveiled as also it was discovered that decomplexation can be triggered by a chemical stimilus.