Absorption and Metabolism of Chlorogenic Acids in Cultured Gastric Epithelial Monolayers

Tracy L. Farrell, Tristan P. Dew, Laure Poquet, Peter Hanson and Gary Williamson

Abstract

Gastric absorption of feruloylquinic acid and di-O-caffeoylquinic acid analogs has never been investigated despite their potential contribution to the proposed beneficial health effects leading to reduced risk of type 2 diabetes. Using a cultured gastric epithelial model, with an acidic apical pH, the relative permeability coefficients (Papp) and metabolic fate of a series of chlorogenic acids (CGAs) were investigated. Mechanistic studies were performed in the apical to basal direction and demonstrated differential rates of absorption for different CGA subgroups. For the first time, we show intact absorption of feruloylquinic acids and caffeoylquinic acid lactones across the gastric epithelium (Papp ～ 0.2 cm/s). Transport seemed to be mainly by passive diffusion, because good linearity was observed over the incubation period and test concentrations, and we speculate that a potential carrier-mediated component may be involved in uptake of certain 4-acyl CGA isomers. In contrast, absorption of intact di-O-caffeoylquinic acids was rapid (Papp ～ 2–10 cm/s) but nonlinear with respect to time and concentration dependence, which was potentially limited by interaction with an efflux transporter and/or pH gradient dependence. For the first time, methylation is shown in gastric mucosa. Furthermore, isoferulic acid, 

Caffeoylquinic acids (5-O-CQA, 4-O-CQA, 3-O-CQA) and di-O-caffeoylqunic acids
(3,5-di-O-caffeoylquinic acid, 3,4-di-O-caffeoylquinic acid, 4,5-di-O-caffeoylquinic acid)
were purchased from Biopurify Pharmaceuticals Ltd. (Sichuan, China).