Faculty of Pharmacy, Shahid Beheshti University, Tehran 14155-6153, Iran.
Fundam Clin Pharmacol. 2011 Dec;25(6):723-33. doi: 10.1111/j.1472-8206.2010.00893.x. Epub 2010 Nov 16.
NF-κB is one of the most important nuclear factors responsible for overexpression of proinflammatory cytokines. This is demonstrated by increased NF-κB activity and other dependent immune factors in inflammatory bowel disease (IBD). Anti-inflammatory effects of silibinin and ursodeoxycholic acid (UDCA) along with their NF-κB inhibitory property are thought to be beneficial in colitis. Trinitrobenzene sulfonic acid was used to induce colitis rat models. After instillation, 48 rats were treated with oral silibinin, UDCA alone or a combination of both. Intraperitoneal dexamethasone was used in the control group. After 12 days of treatment, colonic samples were tested for the severity of mucosal damage macroscopically and microscopically. The levels of activated NF-κB, IL-1β, TNF-α, myeloperoxidase, thiobarbituric acid reactive substances (TBARS), protein carbonyl, and the antioxidant power of the bowel homogenates were determined. The results indicated a significant reduction in NF-κB activity as well as the levels of IL-1β, TNF-α, TBARS, protein carbonyl, myeloperoxidase activity, and an improvement in antioxidant power of colitis in treated rats. Combination therapy resulted in a more prominent improvement in bowel antioxidant power and myeloperoxidase activity. In conclusion, combination of silibinin and UDCA by inhibition of NF-κB and other relevant inflammatory factors of colitis is a good candidate for management of Crohn's disease.
NF-κB 是负责促炎细胞因子过度表达的最重要的核因子之一。在炎症性肠病 (IBD) 中,NF-κB 活性和其他依赖免疫的因子增加证明了这一点。水飞蓟宾和熊去氧胆酸 (UDCA) 的抗炎作用及其 NF-κB 抑制特性被认为对结肠炎有益。三硝基苯磺酸用于诱导结肠炎大鼠模型。滴注后,48 只大鼠用口服水飞蓟宾、UDCA 单独或两者联合治疗。对照组给予腹腔内地塞米松。治疗 12 天后,对结肠样本进行宏观和微观评估以检测黏膜损伤的严重程度。测定激活的 NF-κB、IL-1β、TNF-α、髓过氧化物酶、硫代巴比妥酸反应物质 (TBARS)、蛋白羰基和肠匀浆的抗氧化能力。结果表明,NF-κB 活性以及 IL-1β、TNF-α、TBARS、蛋白羰基、髓过氧化物酶活性降低,结肠炎大鼠的抗氧化能力得到改善。联合治疗可更显著改善肠抗氧化能力和髓过氧化物酶活性。总之,通过抑制 NF-κB 和结肠炎的其他相关炎症因子,水飞蓟宾和 UDCA 的联合治疗是治疗克罗恩病的一个很好的候选药物。