Hesperidin Protects Against Intestinal Inflammation by Restoring Intestinal Barrier Function and Up‐Regulating Treg Cells

Abstract

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-α/ IFN-γ 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-α/IFN-γ -induced reduction in TEER and morphological disruption. Moreover, hesperidin also decreases the epithelial permeability and suppresses proinflammatory responses.

Citrus limon Peel Powder Reduces Intestinal Barrier Defects and Inflammation in a Colitic Murine Experimental Model

“…In addition, feeding mice MetOH extract partly, but significantly, reduced DSS-induced Cxcl2 expression in colonic tissues. Previous studies showed that oral administration of hesperidin (10-40 mg/kg bodyweight) and eriocitrin (20 mg/kg bodyweight) reduces disease symptoms in DSS-induced colitic mice [56,57]. The doses of hesperidin and eriocitrin achieved through feeding mice whole LP powder and MetOH extract were approximately equivalent to 17 and 7 mg/kg bodyweight, respectively, under the feeding conditions of this study.…”

“…The doses of hesperidin and eriocitrin achieved through feeding mice whole LP powder and MetOH extract were approximately equivalent to 17 and 7 mg/kg bodyweight, respectively, under the feeding conditions of this study. At least, hesperidin in whole LP powder and MetOH extract could be expected to exhibit ameliorative effects on colitic mice [57]. The reason for the weaker ameliorative effect of the MetOH extract than that was expected might be due to minor differences in experimental conditions.…”

“…The reason for the weaker ameliorative effect of the MetOH extract than that was expected might be due to minor differences in experimental conditions. Previously, hesperidin was administered to C57BL/6 mice by oral gavage [57], whereas, in this study, whole LP powder was mixed in the diet and provided to Balb/c mice.…”

Exploring the effects of phenolic compounds to reduce intestinal damage and improve the intestinal barrier integrity: A systematic review of in vivo animal studies

“…Most of the included studies assessed different PCs individually, with the exception of two studies where resveratrol and curcumin were evaluated separately in the same experiment [35,46]. In in vivo animal studies, resveratrol as an extract was the most commonly used source of PCs (n ¼ 6) [31,32,34,35,44,45]; after its oral (n ¼ 5) [31,34,35,44,45], or intravenous administration (n ¼ 1) [32].…”

“…The effects of the oral administration of a daily 10, 20, or 40 mg/kg hesperidin doses (HED: 0.8, 1.6, or 3.2 mg/kg) on a DSSinduced intestinal inflammation were assessed on 30 C57BL/6 mice [46]. For the treatment, the hesperidin doses were administered from day 0 until day 13, while the intestinal inflammation was induced from day 0 until day 7 from the oral DSS administration [46].…”