Quercetin and Chlorogenic Acid Mitigate DSS-Induced Changes in Expression of Select Pro-Inflammatory Cytokines and Short Chain Fatty Acid Transporter Genes
Abstract
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.