Protective effect of naringenin against experimental colitis via suppression of Toll-like receptor 4/NF-κB signalling

被引:197
作者
Dou, Wei [1 ,2 ,3 ,4 ]
Zhang, Jingjing [1 ,2 ,5 ]
Sun, Aning [1 ,2 ,5 ]
Zhang, Eryun [1 ,2 ,5 ]
Ding, Lili [1 ,2 ]
Mukherjee, Subhajit [3 ,4 ]
Wei, Xiaohui [1 ,2 ]
Chou, Guixin [6 ]
Wang, Zheng-Tao [1 ,2 ,6 ]
Mani, Sridhar [3 ,4 ]
机构
[1] Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, Shanghai Key Lab Formulated Chinese Med, Shanghai 201203, Peoples R China
[2] Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, MOE Key Lab Standardizat Chinese Med, Shanghai 201203, Peoples R China
[3] Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA
[4] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10461 USA
[5] China Pharmaceut Univ, Dept Pharmacognosy, Nanjing 210038, Jiangsu, Peoples R China
[6] Shanghai R&D Ctr Standardizat Tradit Chinese Med, Shanghai 201203, Peoples R China
基金
上海市自然科学基金; 美国国家卫生研究院; 中国国家自然科学基金;
关键词
Dextran sulphate sodium-induced colitis; Toll-like receptor 4: NF-kappa B; Signalling pathways; Naringenin; NF-KAPPA-B; INFLAMMATORY-BOWEL-DISEASE; MURINE MODEL; ACTIVATION; LIPOPOLYSACCHARIDE; EXPRESSION; RESPONSIVENESS; RECRUITMENT; ANTAGONIST; INHIBITION;
D O I
10.1017/S0007114512005594
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
Naringenin, one of the most abundant flavonoids in citrus, grapefruits and tomatoes, has been used as a traditional anti-inflammatory agent for centuries. However, the molecular mechanism of naringenin in intestinal inflammation remains unknown so far. The present study investigated a molecular basis for the protective effect of naringenin in dextran sulphate sodium-induced murine colitis. Pre-administration of naringenin significantly reduced the severity of colitis and resulted in down-regulation of pro-inflammatory mediators (inducible NO synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), cyclo-oxygenase-2 (Cox2), TNF-alpha and IL-6 mRNA) in the colon mucosa. The decline in the production of pro-inflammatory cytokines, specifically TNF-alpha and IL-6, correlated with a decrease in mucosal Toll-like receptor 4 (TLR4) mRNA and protein. Phospho-NF-kappa B p65 protein was significantly decreased, which correlated with a similar decrease in phospho-I kappa B alpha protein. Consistent with the in vivo results, naringenin exposure blocked lipopolysaccharide-stimulated nuclear translocation of NF-kappa B p65 in mouse macrophage RAW264.7 cells. In addition, in vitro NF-kappa B reporter assays performed on human colonic HT-29 cells exposed to naringenin demonstrated a significant inhibition of TNF-alpha-induced NF-kappa B luciferase expression. Thus, for the first time, the present study indicates that targeted inhibition of the TLR4/NF-kappa B signalling pathway might be an important mechanism for naringenin in abrogating experimental colitis.
引用
收藏
页码:599 / 608
页数:10
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