title: Flavonolignan 2,3-dehydroderivatives: Preparation, antiradical and cytoprotective activity.
abstract: The protective constituents of silymarin, an extract from Silybum marianum fruits, have been extensively studied in terms of their antioxidant and hepatoprotective activities. Here, we explore the electron-donor properties of the major silymarin flavonolignans. Silybin (SB), silychristin (SCH), silydianin (SD) and their respective 2,3-dehydroderivatives (DHSB, DHSCH and DHSD) were oxidized electrochemically and their antiradical/antioxidant properties were investigated. Namely, Folin-Ciocalteau reduction, DPPH and ABTS(+) radical scavenging, inhibition of microsomal lipid peroxidation and cytoprotective effects against tert-butyl hydroperoxide-induced damage to a human hepatocellular carcinoma HepG2 cell line were evaluated. Due to the presence of the highly reactive C3-OH group and the C-2,3 double bond (ring C) allowing electron delocalization across the whole structure in the 2,3-dehydroderivatives, these compounds are much more easily oxidized than the corresponding flavonolignans SB, SCH and SD. This finding was unequivocally confirmed not only by experimental approaches, but also by density functional theory (DFT) calculations. The hierarchy in terms of ability to undergo electrochemical oxidation (DHSCH~DHSD>DHSB>>SCH/SD>SB) was consistent with their antiradical activities, mainly DPPH scavenging, as well as in vitro cytoprotection of HepG2 cells. The results are discussed in the context of the antioxidant vs. prooxidant activities of flavonolignans and molecular interactions in complex biological systems.
authors.affiliation: Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, 775 15 Olomouc, Czech Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Pyszková
authors.affiliation: Department of Biophysics, Centre of the Region Haná for Biotechnological and Agricultural Research, Faculty of Science, Palacký University, tř. 17 listopadu 12, 771 46 Olomouc, Czech Republic; INSERM UMR 850, Univ. Limoges, School of Pharmacy, 2 rue du Docteur Marcland, 87025 Limoges, France.
authors.forename: Michal
authors.initials: M
authors.lastname: Biler
authors.affiliation: Institute of Microbiology, Laboratory of Biotransformation, Czech Academy of Sciences, Vídeňská 1083, 142 20 Prague, Czech Republic.
authors.forename: David
authors.initials: D
authors.lastname: Biedermann
authors.affiliation: Institute of Microbiology, Laboratory of Biotransformation, Czech Academy of Sciences, Vídeňská 1083, 142 20 Prague, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Valentová
authors.affiliation: Institute of Microbiology, Laboratory of Biotransformation, Czech Academy of Sciences, Vídeňská 1083, 142 20 Prague, Czech Republic.
authors.forename: Marek
authors.initials: M
authors.lastname: Kuzma
authors.affiliation: Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, 775 15 Olomouc, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Vrba
authors.affiliation: Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, 775 15 Olomouc, Czech Republic.
authors.forename: Jitka
authors.initials: J
authors.lastname: Ulrichová
authors.affiliation: J. Heyrovský Institute of Physical Chemistry, Czech Academy of Sciences, Dolejškova 3, 182 23 Prague 8, Czech Republic.
authors.forename: Romana
authors.initials: R
authors.lastname: Sokolová
authors.affiliation: Faculty of Physical Chemistry, University of Belgrade, Studentski trg 12-16, 11158 Belgrade, Serbia.
authors.forename: Miloš
authors.initials: M
authors.lastname: Mojović
authors.affiliation: Faculty of Physical Chemistry, University of Belgrade, Studentski trg 12-16, 11158 Belgrade, Serbia.
authors.forename: Ana
authors.initials: A
authors.lastname: Popović-Bijelić
authors.affiliation: Department of Biophysics, Centre of the Region Haná for Biotechnological and Agricultural Research, Faculty of Science, Palacký University, tř. 17 listopadu 12, 771 46 Olomouc, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Kubala
authors.affiliation: INSERM UMR 850, Univ. Limoges, School of Pharmacy, 2 rue du Docteur Marcland, 87025 Limoges, France; Department of Physical Chemistry, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University, tř. 17 listopadu 12, 771 46 Olomouc, Czech Republic.
authors.forename: Patrick
authors.initials: P
authors.lastname: Trouillas
authors.affiliation: Institute of Microbiology, Laboratory of Biotransformation, Czech Academy of Sciences, Vídeňská 1083, 142 20 Prague, Czech Republic.
authors.forename: Vladimír
authors.initials: V
authors.lastname: Křen
authors.affiliation: Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, 775 15 Olomouc, Czech Republic. Electronic address: jan.vacek@upol.cz.
authors.forename: Jan
authors.initials: J
authors.lastname: Vacek
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D019610:Cytoprotection; D004578:Electron Spin Resonance Spectroscopy; D044947:Flavonolignans / Q000737:chemistry / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D008297:Male; D051381:Rats; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D044947:Flavonolignans; D012838:Silymarin; D000077385:Silybin; C015505:silidianin; C015504:silychristin
keywords: Antioxidants; Aryloxy radicals; Electron transfer; Flavonolignans; Hydrogen transfer; Oxidation