title: Mechanism of the antioxidant action of silybin and 2,3-dehydrosilybin flavonolignans: a joint experimental and theoretical study.
abstract: Flavonolignans from silymarin, the standardized plant extract obtained from thistle, exhibit various antioxidant activities, which correlate with the other biological and therapeutic properties of that extract. To highlight the mode of action of flavonolignans as free radical scavengers and antioxidants, 10 flavonolignans, selectively methylated at different positions, were tested in vitro for their capacity to scavenge radicals (DPPH and superoxide) and to inhibit the lipid peroxidation induced on microsome membranes. The results are rationalized on the basis of (i) the oxidation potentials experimentally obtained by cyclic voltammetry and (ii) the theoretical redox properties obtained by quantum-chemical calculations (using a polarizable continuum model (PCM)-density functional theory (DFT) approach) of the ionization potentials and the O-H bond dissociation enthalpies (BDEs) of each OH group of the 10 compounds. We clearly establish the importance of the 3-OH and 20-OH groups as H donors, in the presence of the 2,3 double bond and the catechol moiety in the E-ring, respectively. For silybin derivatives (i.e., in the absence of the 2,3 double bond), secondary mechanisms (i.e., electron transfer (ET) mechanism and adduct formation with radicals) could become more important (or predominant) as the active sites for H atom transfer (HAT) mechanism are much less effective (high BDEs).
authors.affiliation: Laboratoire de Biophysique, Université de Limoges, 2 rue du Docteur Marcland, 87025 Limoges, France. trouillas@unilim.fr
authors.forename: Patrick
authors.initials: P
authors.lastname: Trouillas
authors.forename: Philippe
authors.initials: P
authors.lastname: Marsal
authors.forename: Alena
authors.initials: A
authors.lastname: Svobodová
authors.forename: Jitka
authors.initials: J
authors.lastname: Vostálová
authors.forename: Radek
authors.initials: R
authors.lastname: Gazák
authors.forename: Jan
authors.initials: J
authors.lastname: Hrbác
authors.forename: Petr
authors.initials: P
authors.lastname: Sedmera
authors.forename: Vladimír
authors.initials: V
authors.lastname: Kren
authors.forename: Roberto
authors.initials: R
authors.lastname: Lazzaroni
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Duroux
authors.forename: Daniela
authors.initials: D
authors.lastname: Walterová
mesh_terms: D000975:Antioxidants / Q000737:chemistry*; D044947:Flavonolignans / Q000737:chemistry*; D006859:Hydrogen / Q000737:chemistry*; D007477:Ions / Q000737:chemistry; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D000077385:Silybin; D012838:Silymarin / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D000975:Antioxidants; D044947:Flavonolignans; D007477:Ions; D012838:Silymarin; D000077385:Silybin; D006859:Hydrogen