Ferulic and Caffeic Acids Are High-Affinity Substrates of the Hepatic Transporter SLC22A7/OAT2

High Resolution Image Download MS PowerPoint Slide Phenolic acids (PAs) are abundant in edible plants and produced in the human body through the metabolism of food-derived phytochemicals by gut microbiota. PAs absorbed from the gut are metabolized in the liver, where they have various beneficial effects. However, the molecular mechanism by which PAs enter the liver from the blood remains unknown. Here, we demonstrate the function of SLC22A7/OAT2 serves as a hepatic uptake transporter for ferulic acid (FA) and caffeic acid (CA). The uptake of FA and CA mediated by OAT2 was saturable with K m values of 25.4 and 52.0 μM, respectively. The uptake of FA and CA in human hepatocytes was inhibited by nicotinate, a typical OAT2 substrate. Uptake studies using PAs derivatives showed that OAT2 recognizes specifically hydroxyl group(s) at the aromatic ring and a carboxyl moiety in PAs. These results suggest that OAT2 is involved in the influx of PAs into the liver.