Xiong Yongjian, Chen Dapeng, Yu Changchun, Lv Bochao, Peng Jinyong, Wang Jingyu, Lin Yuan
Department of Pharmacology, Dalian Medical University, Dalian, P. R. China.
Mol Nutr Food Res. 2015 May;59(5):829-42. doi: 10.1002/mnfr.201400614. Epub 2015 Mar 16.
Inflammatory bowel disease is a chronic inflammatory disorder of the gastrointestinal tract. Citrus nobiletin can exert robust anti-inflammatory effects in vivo and in vitro. We evaluated the impact of nobiletin on the excessive inflammatory response and impaired barrier function in a rodent colitis model.
Colitis was established by infusion with 1 mL 2,4,6-trinitrobenzene sulfonic acid (TNBS) dissolved in ethanol (40% v/v) in rats at a 125 mg/kg dose. Caco-2 cell monolayer exposed to LPSs is used as a culture model for intestinal permeability measurements. Nobiletin decreased rat epithelial proinflammatory cytokines and mediators production. Nobiletin restored impaired barrier function in colitic rats and Caco-2 monolayer. Nobiletin decreased protein expressions of Akt, nuclear factor-kappa B (NF-κB), and myosin light chain kinase (MLCK) isolated from rat intestinal epithelial tissue and Caco-2 cell, respectively. PI3K inhibitor or siRNA targeting of either Akt or NF-κB mitigated the impact of nobiletin on MLCK expression and barrier function in Caco-2 monolayer, respectively.
Nobiletin exerted anti-inflammatory effects in TNBS-induced colitis through the downregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) expression. Nobiletin restored barrier function, which had been damaged after TNBS administration, through the inhibition of the Akt-NF-κB-MLCK pathway.
炎症性肠病是一种胃肠道的慢性炎症性疾病。柑橘黄酮在体内和体外均可发挥强大的抗炎作用。我们评估了柑橘黄酮对啮齿动物结肠炎模型中过度炎症反应和受损屏障功能的影响。
通过以125mg/kg的剂量向大鼠输注1mL溶解于乙醇（40% v/v）中的2,4,6-三硝基苯磺酸（TNBS）来建立结肠炎模型。将暴露于脂多糖的Caco-2细胞单层用作肠道通透性测量的培养模型。柑橘黄酮可降低大鼠上皮促炎细胞因子和介质的产生。柑橘黄酮可恢复结肠炎大鼠和Caco-2单层受损的屏障功能。柑橘黄酮分别降低了从大鼠肠上皮组织和Caco-2细胞中分离出的Akt、核因子-κB（NF-κB）和肌球蛋白轻链激酶（MLCK）的蛋白表达。PI3K抑制剂或针对Akt或NF-κB的siRNA分别减轻了柑橘黄酮对Caco-2单层中MLCK表达和屏障功能的影响。
柑橘黄酮通过下调诱导型一氧化氮合酶（iNOS）和环氧化酶2（COX-2）的表达在TNBS诱导的结肠炎中发挥抗炎作用。柑橘黄酮通过抑制Akt-NF-κB-MLCK途径恢复了TNBS给药后受损的屏障功能。
