Onion Peel Extract Prevents Intestinal Inflammation via AMK-Activated Protein Kinase Activation in Caco-2/HT-29 Cells

Background: Obesogenic diets cause intestinal inflammation and dysfunction. Polyphenols have shown a positive impact on reducing inflammation in in vitro studies. However, their bioactivity may not be the same in the in vivo system due to structural alteration by the gastrointestinal digestive process. The purpose of this study was to investigate the anti-inflammatory effect of onion peel and its major bioactive compound, quercetin, in the intestine and further examine the impact of intestinal digestion on this effect. Methods: Onion peel extract (OPE) and quercetin (Q) were digested using gastrointestinal digestive enzymes in vitro and then treated into lipopolysaccharide (LPS)-stimulated Caco-2/HT-29 cells. Genes and proteins related to tight junction, inflammation, and epithelial integrity were measured. Results: OPE and digested OPE (DOPE) had a higher protective effect on LPS-induced tight junction and inflammatory genes and paracellular permeability than Q and digested Q (DQ). DOPE was more effective than OPE, while digestion did not change the activity of Q. The anti-inflammatory effect of OPE and Q with or without digestion was achieved by inhibiting nuclear factor kappa B through AMP-activated protein kinase-activated silent mating-type information regulation 2 homolog 1. Conclusions: It was the first to find that a crude extract, after undergoing gastrointestinal digestion, demonstrated a notably superior anti-inflammatory effect in the cell study, suggesting the consumption of onion peels could potentially yield similar benefits in the human intestine. This discovery underscores the potential of onion peel polyphenols in combating intestinal inflammation, making them a compelling area of research for future therapeutic applications using food byproducts.