Flavonoids inhibit the formation of the cross-linking AGE pentosidine in collagen incubated with glucose, according to their structure.
BACKGROUND
Glycoxidation of collagens contributes to development of vascular complications in diabetes.


OBJECTIVE
Since flavonoids are potent antioxidants present in vegetal foods, it was interesting to examine their effect on the formation of a cross-linking advanced glycation endproduct, pentosidine, in collagens.


METHODS
Collagen was incubated with glucose (250 mM), in the presence of different flavonoids. Pentosidine was measured by HPLC, hydroxyproline colorimetrically.


RESULTS
Monomeric flavonoids (25 and 250 microM) markedly reduced pentosidine/hydroxyproline values in a concentration- and structure-dependent manner. In decreasing order of their specific inhibitory activity, they rank as follows: myricetin > or = quercetin > rutin > (+)catechin > kaempferol. Thus 3'-OH or 4-oxo + Delta(2-3) increase the inhibitory activity; conjugation by Rha-Glc on 3-OH decreases it. Procyanidin oligomers from grape seed were more active than pine bark procyanidin oligomers: this may be related to the galloyl residues present in grape seed oligomers only. Procyanidin oligomers are known to be cleaved into monomers in the gastric milieu and monomeric flavonoids to be absorbed and recovered at micromolar concentrations (with a long plasmatic half-life) in extracellular fluids, in contact with collagens.


CONCLUSIONS
Flavonoids are very potent inhibitors of pentosidine formation in collagens. They are active at micromolar concentrations; these might be achieved in plasma of diabetic patients after oral intake of natural flavonoids.
Urios
Paul
P
Equipe de recherche "Protéines modifiées, protéases et physiopathologie de l'endothélium vasculaire", Dépt. de Biochimie, Faculté de Médecine and Laboratoire de Pharmacologie, Faculté de Pharmacie, Université René Descartes, Paris, France.
Grigorova-Borsos
Anne-Marie
AM
Sternberg
Michel
M
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives* / Q000032:analysis / Q000037:antagonists & inhibitors; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000032:analysis / Q000037:antagonists & inhibitors*; D006031:Glycosylation; D006801:Humans; D006909:Hydroxyproline / Q000032:analysis / Q000494:pharmacology; D008239:Lysine / Q000031:analogs & derivatives* / Q000032:analysis / Q000037:antagonists & inhibitors; D010084:Oxidation-Reduction; D013710:Tendons; D046509:Tissue Culture Techniques
D000975:Antioxidants; D003432:Cross-Linking Reagents; D005419:Flavonoids; D017127:Glycation End Products, Advanced; D001120:Arginine; C062187:pentosidine; D005947:Glucose; D008239:Lysine; D006909:Hydroxyproline