Dietary A- and B-type procyanidins : characterization and biofunctional potential of an abundant and diverse group of phenolics

Abstract

Procyanidins (PCs) are phenolic compounds that belong to the class of flavonoids and are oligomers of monomeric (epi)catechin units. These monomeric units can be linked to each other by a single C4-C8 or C4-C6 linkage, which is referred to as B-type. Besides these single linkages an additional ether bond can be present, C2-O-C7 or C2-O-C5, which is referred to as A-type. PCs are highly abundant in our diet. Well known PC food sources are cocoa, apple, grape seeds, wine and nuts. After the intake of PC-rich sources health beneficial effects have been detected, which are mainly related to the prevention of cardiovascular diseases such as lowering of blood pressure. The aims of this thesis were to study the bioavailability, bioconversion and bioactivity of purified PCs. Therefore, we first developed techniques for the efficient purification of both A- and B-type PCs from peanut skins and grape seeds, respectively. Furthermore, tools were set-up to analyze and characterize individual PCs in complex mixtures. We showed that A-type PC dimers were absorbed from the small intestine of rats and that they were better absorbed than B-type PC dimers. The PC dimers were not conjugated or methylated upon absorption in contrast to their monomeric units (epi)catechin. Furthermore, the presence of A-type PC tetramers enhanced the absorption of B-type PC dimers. The microbial conversion of B-type PC dimers was studied by exposing them to human microbiota. The main microbial metabolites were 2-(3,4-dihydroxyphenylacetic acid and 5-(3,4-dihydroxyphenyl)-γ-valerolactone. Based on these and other metabolites that were detected, a tentative microbial degradation route was proposed for B-type PC dimers, in which the interflavanic bond does not need to be cleaved upon degradation. Subsequently, the vasorelaxing potential of purified PCs and their microbial metabolites was analyzed by measuring their effect on the NO production of endothelial cells. Both A- and B-type PCs showed a tendency (insignificant) to increase NO production with increasing degree of polymerization and several of their human microbial metabolites that were tested were inactive. Besides enhancing NO production, several other mechanisms could be targets of PCs and were also discussed. This thesis increased our knowledge on the absorption, biotransformation and bioactivity of A- and B-type PCs. A possible interaction between oligomers with a high and low degree of polymerization, influencing absorption processes has been discussed, which suggests that until now the biofunctional potential of PAs has been underestimated. <br/