(PTFS04-01-25) Quercetin Improved High-Fat Diet-Induced Inflammation and Oxidative Stress in Intestine

Objectives: Obesogenic diet leads to intestinal inflammation by producing pro-inflammatory mediators and reactive oxygen species, which results in intestinal dysfunction and increases the risk of developing metabolic diseases. This study aimed to investigate the mechanism by which quercetin decreases intestinal inflammation and oxidative stress in vivo.

Methods: Mice were fed a low-fat diet (LFD) or a high-fat diet (HFD) with or without 1% quercetin. Genes, microRNA, and proteins related to tight junction, inflammation, and antioxidants were measured in the intestine using a qPCR or a western blot. Inflammatory markers were measured in blood. Intestinal permeability was determined by the serum levels of FITC-dextran.


Results: Quercetin alleviated HFD-induced inflammation and impaired cellular defense by reducing cyclooxygenase 2, tumor necrosis factor-α, monocyte chemoattractant protein-1, and interleukin 6 and 1b and increasing genes related to antioxidant enzymes, superoxide dismutase 2 and 3, glutathione peroxidase 1, and catalase through modulating nuclear factor kappa B (NF-κB) and nuclear factor erythroid 2-related factor (NRF) 2 in the intestine. HFD-fed mice supplemented with quercetin exhibited improved intestinal permeability with increased tight junction proteins, zonula occludens, occludin, and claudin1, and genes related to mucin production such as free fatty acid receptor 2 and 3 and mucin 2 in the intestine, compared to HFD-fed mice. The genes related to antioxidants, tight junction, and mucin were also induced by quercetin in the intestine of LFD-fed mice. Consistent with changed serotonin transporter and 5-hydroxytryptamine receptor 7 genes in the intestine, quercetin decreased lipopolysaccharide, cluster of differentiation 14, and LPS-binding protein levels, and myeloperoxidase activity in the blood of HFD-fed mice. The anti-inflammatory effect of quercetin in the intestine was attributed to AMP-activated protein kinase-silent mating type information regulation 2 homolog 1-NF-κB or NRF2-NF-κB signaling through increased miRNA-16-5p and miRNA-200b-3p, which suppresses inflammation and promotes tight junction.

Conclusions: Quercetin has the potential to enhance intestinal function by alleviating inflammation and oxidative stress in the intestine.

Funding Sources: USDA