Tangeretin Inhibits IL-12 Expression and NF-κB Activation in Dendritic Cells and Attenuates Colitis in Mice

Abstract

In the preliminary study, tangeretin (5,6,7,8,4'-pentamethoxy flavone), a major constituent of the pericarp of sp., inhibited TNF-, IL-12, and IL-23 expression and nuclear factor kappa-B activation in lipopolysaccharide-stimulated dendritic cells; however, it did not affect IL-10 expression. Furthermore, tangeretin (5, 10, and 20 µM) suppressed the activation and translocation of nuclear factor kappa-B (p65) into the nuclei by inhibiting the binding of lipopolysaccharide on dendritic cells. Oral administration of tangeretin (10 and 20 mg/kg) suppressed the inflammatory responses, such as nuclear factor kappa-B and mitogen-activated protein kinase activation and myeloperoxidase activity, in the colon of mice with 2,4,6-trinitrobenzene sulfonic acid-induced colitis. Tangeretin increased 2,4,6-trinitrobenzene sulfonic acid-suppressed expression of tight junction proteins occludin, claudin-1, and ZO-1. Tangeretin also inhibited 2,4,6-trinitrobenzene sulfonic acid-induced differentiation of Th1 and Th17 cells as well as the expression of T-bet, RORt, interferon-, IL-12, IL-17, and TNF-. However, tangeretin increased 2,4,6-trinitrobenzene sulfonic acid-suppressed differentiation of regulatory T cells as well as the expression of Foxp3 and IL-10. These results suggest that oral administration of tangeretin may attenuate colitis by suppressing IL-12 and TNF- expression and nuclear factor kappa-B activation through the inhibition of lipopolysaccharide binding on immune cells such as dendritic cells.

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

“…It was shown that hesperidin had protective effects on the intestine through their antioxidant and anti‐inflammatory activities . Some studies also reported that hesperidin could inhibit inflammatory response induced by Aeromonas hydrophila infection and alter the ratio of CD4 + /CD8 + T cells 15.…”

Anti-inflammatory effects of polymethoxyflavones from citrus peels: a review

“…These findings verified that the inflammatory effect of nobiletin may broadly count on the suppression of PI3K/Akt pathway as well as the activated NF-κB, which serves as crucial hub of the whole inflammatory pathway. The anti-inflammatory effect of tangeretin on LPS-induced bone marrow cells and colitic mice was respectively examined (Eun et al, 2017). In both models, tangeretin significantly suppressed IL-12 and TNF-α expression by regulating NF-κB, as well as the iNOS and COX-2 generation.…”

Preventive Effects of an UPLC-DAD-MS/MS Fingerprinted Hydroalcoholic Extract of Citrus aurantium in a Mouse Model of Ulcerative Colitis

“…Among the various types of identified phytochemicals in HECA, the therapeutic effects of coumarins (e.g., scopoletin and isoimperatorin), flavonoids (e.g., hesperidin, isoquercetin, miscanthoside, naringin, naringenin, nobiletin, poncirin, quercetin, rutin, tangeritin, vitexin), lignans (e.g., acanthoside D), phenolics (e.g., ferulic acid), and sesquiterpenes (e.g., abscisic acid) have been reported against UC in animal models and human studies [12,17,[24][25][26][27][28][29][30][31][32][33][34]. These phytochemicals inhibited the overproduction of inflammatory mediators (e.g., TNF-α, IL-1β, IL-4, IL-6, IL-17, and continued prostaglandin E 2 ) and oxidative stress (e.g., nitric oxide, myeloperoxidase, superoxide dismutase, and malonaldehyde) while improving colonic structural damage (e.g., occludin, claudin-1, and zona occludens protein-1).…”