In vitro intestinal transport of oligomeric procyanidins (DP 2 to 4) across monolayers of Caco-2 cells

Extracts from hawthorn leafs and flowers (Crataegus sp., Rosaceae) are widely used as a rational based phytomedicine for declining cardiac performance. According to present literature C-glycosylated flavones and oligomeric procyanidins are considered to be the active ingredients, despite the fact that no systematic data are available on systemic bioavailability of proanthocyanidins after oral intake. The present study aims to review the actual state of literature in this field and to investigate the intestinal absorption mechanisms of defined hawthorn PAs with different degrees of polymerization by validated in vitro Caco-2 monolayer permeation system. Hawthorn OPCs with DP 2 to 6 were isolated as defined clusters. Procyanidin 82 and the procyanidin clusters DP 4, 5 and 6 had very low P,pp values between 0.6 and 6 x 10(-7) cm/s for apical to basolateral permeation. The higher the molecular weight the lower permeation coefficients were calculated. The observed low-level transport was mainly due to passive paracellular permeation. Additionally cellular uptake of OPCs by transcellular permeation was possible: on the other side procyanidins were shown to be p-glycoprotein substrates, which leads to subsequent excretion of PAs by the efflux pump to the apical side. Mixtures of the different OPCs did not have an increased permeation. Transport experiments of complex OPC mixtures together with hawthorn flavonoids did not indicate any improved permeation or synergistic effects. In principle this raises the question if systemic pharmacological activities of hawthorn extracts, can really be attributed to OPCs with very low systemic bioavailability. (C) 2012 Elsevier B.V. All rights reserved.