Tangeretin Inhibits IL-12 Expression and NF-κB Activation in Dendritic Cells and Attenuates Colitis in Mice.
In the preliminary study, tangeretin (5,6,7,8,4'-pentamethoxy flavone), a major constituent of the pericarp ofCitrussp., inhibited TNF-α, 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 nucleiin vitroby 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, RORγt, interferon-γ, IL-12, IL-17, and TNF-α. 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-αexpression and nuclear factor kappa-B activation through the inhibition of lipopolysaccharide binding on immune cells such as dendritic cells.
Department of Life and Nanopharmaceutical Sciences and Department of Pharmacy, Kyung Hee University, Seoul, Korea.
Su-Hyeon
SH
Eun
Research Institute for Biological Functions, Chubu University, Aichi, Japan.
Je-Te
JT
Woo
Department of Life and Nanopharmaceutical Sciences and Department of Pharmacy, Kyung Hee University, Seoul, Korea.
Dong-Hyun
DH
Kim
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D002957:Citrus / Q000737:chemistry*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000187:drug effects* / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D047309:Flavones / Q000737:chemistry / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism; D014301:Trinitrobenzenes / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid / Q000009:adverse effects
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D047309:Flavones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014301:Trinitrobenzenes; C029222:sym-trinitrobenzene; D014302:Trinitrobenzenesulfonic Acid; D020928:Mitogen-Activated Protein Kinases; C059006:tangeretin