Hesperidin Protects Against Intestinal Inflammation by Restoring Intestinal Barrier Function and Up-Regulating Treg Cells (vol 63, 1800975, 2019)

Scope Hesperidin is an important natural phenolic compound and is considered beneficial to health. The purpose of this study is to investigate the protective effects of hesperidin on DSS-induced colitis in mice and Caco-2 cells. Methods The DSS-induced colitis mice are assigned to 10, 20, and 40 mg kg(-g) hesperidin diets after DSS treatment. For in vitro experiments, Caco-2 cells are treated with TNF-alpha/ IFN-gamma for 48 h without or with hesperidin. Results Hesperidin supplementation ameliorates DSS-induced colitis. Specifically, hesperidin ameliorates intestinal inflammation through decreasing MDA activity and enhancing SOD and GSH activities. Hesperidin also obviously upregulates Nrf2 antioxidant pathway and increases the protein expression of HO-1 and NQO1. Additionally, hesperidin significantly reduces the levels of inflammatory factors and increases the levels of anti-inflammatory factors in the colon tissues. Further analysis shows that hesperidin can improve the expression of tight junction proteins and intestinal permeability, as well as increases the Treg population. In Caco-2 cells, it is shown that hesperidin prevents TNF-alpha/IFN-gamma-induced reduction in TEER and morphological disruption. Moreover, hesperidin also decreases the epithelial permeability and suppresses proinflammatory responses. Conclusion Hesperidin can protect against intestinal inflammation via enhanced Nrf2 antioxidant pathway, increases the Treg population, and restores intestinal barrier function.