Tetramethylated dimeric procyanidins are detected in rat plasma and liver early after oral administration of synthetic oligomeric procyanidins.
Procyanidins (PC) are of great interest in nutrition because they account for a major fraction of the total flavonoids ingested in Western diets and have health benefits in humans. However, it remains unknown which species of PC, namely, monomers, oligomers, or aromatic acid derivatives of gut microflora, are responsible for their beneficial effects in vivo. The high molecular complexity of PC extracts and PC-rich foods is a major problem in absorption studies. To circumvent this difficulty, we have synthesized oligomeric PC consisting of (-)-epicatechin units linked by ethyl bridges. The synthetic PC (SPC) only contains dimers, trimers, tetramers, and nanomers. After oral gavage of this SPC (200 mg/kg body weight) to male Wistar rats, tetramethylated dimeric PC (TDPC) were detected in plasma and liver. TDPC were detected in plasma as soon as 1 h after intake, reaching maximum concentrations (14 mg/L) 2 h after gavage. At this time, liver contained as much as 15 mug of TDPC per gram of tissue. In conclusion, orally administered dimeric PC are rapidly absorbed and internally methylated in rats. To our knowledge, this is the first time that methylated dimeric PC have been detected in plasma and liver. We consider that plasma and liver concentrations of TDPC are sufficient to exert a hormone-like effect and, therefore, that PC dimers are good candidates as agents of the biological activities of PC extracts and PC-rich foods.
Departament de Bioquímica i Biotecnologia, CeRTA, Universitat Rovira i Virgili, Marcel.lí Domingo s/n, 43007 Tarragona, Spain.
Bernardino
B
García-Ramírez
Juan
J
Fernandez-Larrea
M Josepa
MJ
Salvadó
Anna
A
Ardèvol
Lluís
L
Arola
Cinta
C
Bladé
D000042:Absorption; D000818:Animals; D044946:Biflavonoids / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D002392:Catechin / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D019281:Dimerization; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000737:chemistry*; D008297:Male; D013058:Mass Spectrometry; D008745:Methylation; D044945:Proanthocyanidins / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D044946:Biflavonoids; D044945:Proanthocyanidins; C017674:procyanidin; D002392:Catechin