Absorption and metabolism of chlorogenic acids in cultured gastric epithelial monolayers

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

Research output: Contribution to journalArticle

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 (P(app)) 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 (P(app) ~ 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 (P(app) ~ 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, dimethoxycinnamic acid, and ferulic acid were identified as novel gastric metabolites of CGA biotransformation. We propose that the stomach is the first location for the release of hydroxycinnamic acids, which could explain their early detection after coffee consumption.
Original languageEnglish
Pages (from-to)2338-2346
Number of pages9
JournalDrug Metabolism and Disposition
Volume39
Issue number12
Early online date21 Sep 2011
DOIs
Publication statusPublished - Dec 2011

Fingerprint

Chlorogenic Acid
Stomach
ferulic acid
Acids
Coumaric Acids
Proton-Motive Force
Coffee
Lactones
Biotransformation
Gastric Mucosa
Type 2 Diabetes Mellitus
Methylation
Permeability
Epithelium
Health
caffeoylquinic acid

Keywords

  • cultured cells
  • chlorogenic acid
  • gastric mucosa
  • humans
  • hydrogen-ion concentration

Cite this

Farrell, Tracy L. ; Dew, Tristan P. ; Poquet, Laure ; Hanson, Peter ; Williamson, Gary. / Absorption and metabolism of chlorogenic acids in cultured gastric epithelial monolayers. In: Drug Metabolism and Disposition. 2011 ; Vol. 39, No. 12. pp. 2338-2346.
@article{ab94a8494f0b48988ccf6760e3ba9bd2,
title = "Absorption and metabolism of chlorogenic acids in cultured gastric epithelial monolayers",
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 (P(app)) 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 (P(app) ~ 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 (P(app) ~ 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, dimethoxycinnamic acid, and ferulic acid were identified as novel gastric metabolites of CGA biotransformation. We propose that the stomach is the first location for the release of hydroxycinnamic acids, which could explain their early detection after coffee consumption.",
keywords = "cultured cells, chlorogenic acid, gastric mucosa, humans, hydrogen-ion concentration",
author = "Farrell, {Tracy L.} and Dew, {Tristan P.} and Laure Poquet and Peter Hanson and Gary Williamson",
year = "2011",
month = "12",
doi = "10.1124/dmd.111.040147",
language = "English",
volume = "39",
pages = "2338--2346",
journal = "Drug Metabolism and Disposition",
issn = "0090-9556",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "12",

}

Absorption and metabolism of chlorogenic acids in cultured gastric epithelial monolayers. / Farrell, Tracy L.; Dew, Tristan P.; Poquet, Laure; Hanson, Peter; Williamson, Gary.

In: Drug Metabolism and Disposition, Vol. 39, No. 12, 12.2011, p. 2338-2346.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Absorption and metabolism of chlorogenic acids in cultured gastric epithelial monolayers

AU - Farrell, Tracy L.

AU - Dew, Tristan P.

AU - Poquet, Laure

AU - Hanson, Peter

AU - Williamson, Gary

PY - 2011/12

Y1 - 2011/12

N2 - 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 (P(app)) 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 (P(app) ~ 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 (P(app) ~ 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, dimethoxycinnamic acid, and ferulic acid were identified as novel gastric metabolites of CGA biotransformation. We propose that the stomach is the first location for the release of hydroxycinnamic acids, which could explain their early detection after coffee consumption.

AB - 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 (P(app)) 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 (P(app) ~ 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 (P(app) ~ 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, dimethoxycinnamic acid, and ferulic acid were identified as novel gastric metabolites of CGA biotransformation. We propose that the stomach is the first location for the release of hydroxycinnamic acids, which could explain their early detection after coffee consumption.

KW - cultured cells

KW - chlorogenic acid

KW - gastric mucosa

KW - humans

KW - hydrogen-ion concentration

UR - http://www.scopus.com/inward/record.url?scp=81855183900&partnerID=8YFLogxK

UR - http://dmd.aspetjournals.org/content/39/12/2338

U2 - 10.1124/dmd.111.040147

DO - 10.1124/dmd.111.040147

M3 - Article

C2 - 21937734

VL - 39

SP - 2338

EP - 2346

JO - Drug Metabolism and Disposition

JF - Drug Metabolism and Disposition

SN - 0090-9556

IS - 12

ER -