Substrate Specificity of the Nateglinide/H+ Cotransport System for Phenolic Acids

In clinical, patients usually take many kinds of drugs at the same time. Thus, drug−drug interactions involving transporters can often directly affect the therapeutic safety and efficacy of many important drugs. However, there have been few studies on food−drug interactions involving transporters. Dietary polyphenols have been widely assumed to be beneficial for human health. Polyphenols are found ubiquitously, and they are commercially prepared and used as functional foods. We have reported that ferulic acid, which is one of the most well-known polyphenols and is used as a functional food, affected the transport of nateglinide, an antidiabetic drug, by Caco-2 cells. In this study, we investigated the effects of other polyphenols on the nateglinide/H+ transport system. We report here that caffeic acid and p-coumaric acid have a different inhibitory manner on the uptake of nateglinide. The results of this study are useful to identify the substrate specificity of the nateglinide/H+ cotransporter. Keywords: Nateglinide; fluorescein; caffeic acid; phenolic acid; transporter