Quercetin and Chlorogenic Acid Mitigate DSS-Induced Changes in Expression of Select Pro-Inflammatory Cytokines and Short Chain Fatty Acid Transporter Genes
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Quercetin (Q) and chlorogenic acid (CA), two bioactive compounds found in stonefruits, may protect against inflammation and cancer because of anti-cancer, anti-oxidant, and anti-inflammatory properties. Since these compounds reach the colon undigested, they affect the luminal environment before they are metabolized by the microbiota and transported into epithelial cells. We hypothesized that Q and CA may suppress expression of pro-inflammatory molecules, alter the luminal environment, and alter the cell cycle, thereby protecting against injury/colitis. To test this hypothesis, 63 male weanling rats were given one of three diets (basal, 0.45% Q, 0.05% CA). After 3 wk of acclimation, colitis was induced in 11 rats/diet [3% dextran sodium sulfate (DSS), 48 h, 3 treatments, 2 wk separation] and 10 rats/diet served as control (0% DSS). All rats were terminated at wk 9. Measurements included: fecal moisture content, fecal short chain fatty acid (SCFA) concentrations (gas chromatography), epithelial injury and inflammation in the distal colon, proliferation (PCNA), and NF-kappaB activity (ELISA method) and gene expression (real time RT-PCR) in mucosal scrapings. Fecal moisture content was significantly increased by DSS exposure (p<0.05), and never returned to control levels. Fecal SCFA concentrations also increased with DSS (acetate, p<0.05; butyrate, p<0.05). Increased SCFA concentrations could indicate decreased SCFA uptake. Experimental diets were able to mitigate DSS-induced decreases in SLC5A8 (SCFA transporter) expression. DSS significantly increased injury (p<0.0001) and inflammation (p<0.01) scores. Compared to the basal diet, CA decreased NF-kappaB activity in DSS-treated rats (p<0.05). Q and CA may maintain healthy regulation of NF-kappaB through maintaining expression levels of IkappaBalpha and Tollip, molecules that inhibit NF-kappaB activation. Q and CA mitigated DSS-induced increases in pro-inflammatory cytokine expression, specifically IL-1. Q enhanced expression of injury-repair molecule FGF-2 (p<0.01), but neither diet nor DSS treatment altered proliferation. Although Q and CA did not protect against DSS-induced increases in injury and inflammation scores or fecal SCFA concentrations, their influence on expression of injury repair molecules, pro-inflammatory cytokines, SCFA transport proteins, and NF-kappaB inhibitory molecules suggests beneficial influences on major pathways involved in DSS-induced injury/inflammation. The combined benefit of these compounds could have additive/synergistic effects and, therefore, deserve further examination.
Piefer, Leigh (2012). Quercetin and Chlorogenic Acid Mitigate DSS-Induced Changes in Expression of Select Pro-Inflammatory Cytokines and Short Chain Fatty Acid Transporter Genes. Master's thesis, Texas A&M University. Available electronically from