UBC Theses and Dissertations
Major chlorogenic acid isomers present in coffee are modulators of redox biology and inflammation in Caco-2 cells Liang, Ningjian
Chlorogenic acid (CGA) is a general term used to describe the most abundant group of phenolic acids in coffee. 3-CQA, 4-CQA, 5-CQA, 3,4-diCQA, 3,5-diCQA, and 4,5-diCQA are major CGAs in coffee; but only 5-CQA has been thoroughly studied. The first objective of this thesis was to study interactions between major CGA isomers and chemical changes in coffee brew that affect antioxidant activity noted for coffee. The second overall objective was to study the potential of these six major CGA isomers in modulating oxidative stress and inflammation using a human intestinal Caco-2 cell line. The findings from Chapter 2 suggested that the other five CGA isomers (4-CQA, 5-CQA, 3,4-diCQA, 3,5-diCQA, and 4,5-diCQA) together account for more than 50% of the total CGA in coffee and contributed to the antioxidant activity of coffee brew. Chapter 3 and 4 addressed the research question of whether these major CGA isomers have a modulating effect on oxidative stress and inflammation in human intestinal Caco-2 cell line. Caco-2 cells were first incubated with, or without, individual CGA isomers, followed by a phorbol 12-myristate 13-acetate plus human interferon gamma challenge. Biomarkers of oxidative stress (intracellular ROS and GSH/GSSG) and inflammation (IL-8) were measured. The results demonstrated that CGA isomers scavenged intracellular ROS in inflamed Caco-2 cells, mitigated the drop in GSH/GSSG ratio and attenuated IL-8 secretion. Dicaffeoylquinic acids (3,4-diCQA, 3,5-diCQA, and 4,5-diCQA) had a relatively stronger capacity to evoke protection compared to caffeoylquinic acids (3-CQA, 4-CQA, and 5-CQA). To elucidate the possible mechanism underlying these actions, the effects of CGA isomers on the nuclear factor kappa B signaling pathway, mitogen-activated protein kinase cascades, and nuclear factor (erythroid-derived 2)-like 2 signaling pathway were further investigated. In conclusion, structural differences in six CGA isomers were found to correspond to differences in antioxidant and anti-inflammation activities. CGA isomers attenuate oxidative stress and inflammation in Caco-2 cells by triggering changes in redox biology parameters, lead to an up-regulation of nuclear factor kappa B signaling at very early stage, mitigation of p38 phosphorylation and up-regulation of antioxidant genes in an intermediate stage, and activation of Nrf2 signaling at a much later stage.
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