The interaction of flavonoids with membranes: potential determinant of flavonoid antioxidant effects.
Twenty six phenolic substances including representatives of the families, flavanones, flavanols and procyanidins, flavonols, isoflavones, phenolic acids and phenylpropanones were investigated for their effects on lipid oxidation, membrane fluidity and membrane integrity. The incubation of synthetic phosphatidylcholine (PC) liposomes in the presence of these phenolics caused the following effects: (a) flavanols, their related procyanidins and flavonols were the most active preventing 2,2'-azo-bis (2,4-dimethylvaleronitrile) (AMVN)-induced 2-thiobarituric acid-reactive substances (TBARS) formation, inducing lipid ordering at the water-lipid interface, and preventing Triton X-100-induced membrane disruption; (b) all the studied compounds inhibited lipid oxidation induced by the water-soluble oxidant 2,2'-azo-bis (2-amidinopropane) (AAPH), and no family-related effects were observed. The protective effects of the studied phenolics on membranes were mainly associated to the hydrophilicity of the compounds, the degree of flavanol oligomerization, and the number of hydroxyl groups in the molecule. The present results support the hypothesis that the chemical structure of phenolics conditions their interactions with membranes. The interactions of flavonoids with the polar head groups of phospholipids, at the lipid-water interface of membranes, should be considered among the factors that contribute to their antioxidant effects.
Erlejman
A G
AG
Department of Biological Chemistry-IQUIFIB (UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, Argentina.
Verstraeten
S V
SV
Fraga
C G
CG
Oteiza
P I
PI
D000578:Amidines / Q000037:antagonists & inhibitors / Q000737:chemistry; D000975:Antioxidants / Q000494:pharmacology*; D001391:Azo Compounds / Q000037:antagonists & inhibitors / Q000737:chemistry; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D008051:Lipid Bilayers / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D008560:Membrane Fluidity / Q000187:drug effects*; D008566:Membranes / Q000737:chemistry / Q000187:drug effects*; D008823:Micelles; D009570:Nitriles / Q000037:antagonists & inhibitors / Q000737:chemistry; D016877:Oxidants / Q000037:antagonists & inhibitors; D010084:Oxidation-Reduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D017392:Thiobarbituric Acid Reactive Substances / Q000737:chemistry
D000578:Amidines; D000975:Antioxidants; D001391:Azo Compounds; D005419:Flavonoids; D008051:Lipid Bilayers; D008055:Lipids; D008081:Liposomes; D008823:Micelles; D009570:Nitriles; D016877:Oxidants; D017392:Thiobarbituric Acid Reactive Substances; C055792:2,2'-azobis(2,4-dimethylvaleronitrile); C046728:2,2'-azobis(2-amidinopropane)