Capacity of chlorogenic acid isomers to modulate oxidative and inflammatory responses in Caco‐2 human enterocyte‐like cells

Chlorogenic acids (CGAs) are esters formed between caffeic and quinic acids, and represent an abundant group of plant polyphenols present in the human diet. CGAs contain different isomers, including the major ones such as 5‐caffeoylqunic acid (5‐CQA), 3‐caffeoylqunic acid, 4‐caffeoylqunic acid, 3,4‐dicaffeoylqunic acid, 3,5‐dicaffeoylquinic acid, and 4,5‐dicaffeoylqunic acid. The antioxidant and anti‐inflammatory properties of 5‐CQA have been established in both cell and animal studies. However, little is known about the ability of other major CGA isomers to modulate oxidative and inflammatory stresses. In this study, we conducted a pre‐treatment experiment in which Caco‐2 cells were exposed to individual physiological relevant concentrations of CGA isomers for 24 hours and once removed were then challenged with oxidative and inflammatory stresses. We found that the pre‐incubation of CGA isomers promoted pro‐inflammatory cytokine, interleukin 8, and activated the nuclear translocation of nuclear factor kappa B (NF‐κB) pathway. The pre‐incubation did not activate nuclear factor‐E2‐related factor 2 (Nrf2) pathway. A co‐incubation experiment was conducted in which Caco‐2 cells were firstly exposed to individual CGA isomers for 24 hours. Then, fresh CGA isomers were added before cells were challenged with oxidative and inflammatory stresses. Herein, we found that the co‐incubation treatment of CGA isomers showed anti‐inflammatory effect by attenuating the secretion of IL‐8. This was accompanied with an increase in NF‐κB signaling. We also found that CGA co‐incubation treatment significantly increased Nrf2 signaling that corresponded to increased ratio of reduced glutathione to oxidized glutathione; both indicating a mitigated oxidative stress. We proposed that CGA isomers exert anti‐inflammatory activity by activating Nrf2 signaling, even though CGA isomer activated NF‐κB pathway at the early stage of response. Our results suggest that Nrf2 is a secondary event that participates in a later negative loop of NF‐kB regulation. Cross‐talk between NF‐κB and Nrf2 seems apparent in this case. Support or Funding Information This work was funded by the Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant.