Effect of luteolin and apigenin on rosmarinic acid bioavailability in Caco-2 cell monolayers

Herbal teas are usually complex mixtures of therapeutically active compounds. The present study is focused on the interference of flavonoids on the bioavailability of rosmarinic acid, as these types of compounds are often present together in decoctions of medicinal plants, namely Lamiaceae species. The bioavailability of rosmarinic acid was analysed in the decoction of P. barbatus and in mixtures with apigenin and luteolin. Rosmarinic acid in the herbal tea showed a 43% bioavailability through the Caco-2 cells when luteolin and apigenin were approximately 30 μM each. In the artificial mixtures the bioavailability could be increased to 90% when the concentration of flavonoids was increased to 90 μM. The co-administration of substrates of known intestinal transport systems, Pgp, Oatp and MCT, showed that the extract components not only modulated the activity of these transporters but also their own bioavailability was dependent on them. Our results demonstrate that plant extracts with a high diversity of polyphenol compounds may have higher bioavailability than that predicted by the isolated compounds. The bioavailability of rosmarinic acid in Caco-2 monolayers is higher in the presence of the flavonoids apigenin and luteolin, as in herbal infusions, due to the MCT and ABC transporters.