The bioavailability of polyphenols is highly governed by the capacity of the intestine and of the liver to secrete conjugated metabolites.
BACKGROUND
After ingestion of a complex meal containing foods and beverages of plant origin, different polyphenols are likely to be simultaneously present in the intestine. However, almost nothing is known about their interactions and possible consequences on their bioavailability.


OBJECTIVE
The present study deals with the intestinal absorption and splanchnic metabolism of three polyphenols, genistein, hesperetin and ferulic acid (FA),when perfused in the small intestine alone or in combination, at different doses (15 and 120 microM).


METHODS
The fate of polyphenols in the small intestine was studied using a rat in situ intestinal perfusion model. Polyphenols were analysed in perfusate, bile and plasma by HPLC.


RESULTS
Whatever the perfused dose, the efficiency of the net transfer towards the enterocyte was similar for the three polyphenols and not significantly modified by any association between these molecules. However, FA largely differed from the two flavonoids by its low intestinal secretion of conjugates. When perfused at 15 microM, the secretion of conjugates back to the lumen represented 6.2% of the net transfer into the enterocytes for FA compared to 25.5 and 20 % for genistein and hesperetin respectively. Intestinal conjugation and secretion of conjugates back to the gut lumen varied with the dose of flavonoids: saturation of conjugation was observed for the highest dose or when a high dose of a second flavonoid was perfused simultaneously. Intensity of the biliary secretion substantially differed among tested polyphenols: 7.7% of the net transfer for FA vs 50% for genistein or hesperetin. The extent of the enterohepatic cycling of these polyphenols was proportional to the perfused dose and unaffected by the simultaneous presence of different compounds in the intestine.


CONCLUSIONS
Genistein and hesperetin appeared less available than FA for peripheral tissues because of a high intestinal and biliary secretion of their conjugates. Moreover, data suggest that a high polyphenol intake may improve their bioavailability due to saturation of the intestinal secretion of conjugates.
Laboratoire des Maladies Métaboliques et des Micronutriments, I. N. R. A. Centre de Recherche de Clermont-Ferrand/Theix, 63122, Saint Genés-Champanelle, France.
M
M
Silberberg
C
C
Morand
T
T
Mathevon
C
C
Besson
C
C
Manach
A
A
Scalbert
C
C
Remesy
D000818:Animals; D001652:Bile Ducts / Q000378:metabolism; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D003373:Coumaric Acids / Q000737:chemistry / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000737:chemistry / Q000493:pharmacokinetics*; D019833:Genistein / Q000737:chemistry / Q000493:pharmacokinetics; D006569:Hesperidin / Q000737:chemistry / Q000493:pharmacokinetics; D007408:Intestinal Absorption / Q000187:drug effects*; D007421:Intestine, Small / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D015394:Molecular Structure; D010477:Perfusion; D010636:Phenols / Q000737:chemistry / Q000493:pharmacokinetics*; D059808:Polyphenols; D051381:Rats; D017208:Rats, Wistar
D003373:Coumaric Acids; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; C004999:ferulic acid; D019833:Genistein; D006569:Hesperidin; C013015:hesperetin