Zhang Yanping, Cao Ping, Qin Dongyuan, Zhao Ying, Chen Xing, Ma Peng
Department of Gastroenterology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, No.99 Longcheng street, Xiao dian District, Taiyuan, 030032, China.
Faculty of Graduate Studies, Shanxi Medical University, NO.56 Road, NO. Xinjiannan Yingze District, Taiyuan, 030000, China.
Inflammopharmacology. 2025 Jan;33(1):341-352. doi: 10.1007/s10787-024-01630-9. Epub 2025 Jan 5.
Ulcerative colitis (UC) is a significant inflammatory bowel disease (IBD) that typically arises from chronic inflammation of the intestinal tract. Report suggest that anti-inflammatory drug plays a crucial role in the protection of UC. The recent study demonstrated that columbianadin has a protective effect against UC induced by dextran sulfate sodium (DSS) in rats through the modulation of HO-1/Nrf2 and TLR4-NF-κB signaling pathways.
In this study, Swiss Wistar rats were utilized, and UC was induced using 2% DSS. The treatment regimen included oral administration of columbianadin (5, 10 and 15 mg/kg) and sulfasalazine to the rats. The body weight, spleen index, disease activity index (DAI), colon length, food and water intake were estimated. Moreover, antioxidant, cytokines, inflammatory and apoptosis parameters were determined. mRNA expression levels were also quantitatively analyzed.
Columbianadin treatment significantly (P < 0.001) boosted the body weight and suppressed the DAI. Columbianadin significantly (P < 0.001) enhanced the colon length and repressed the spleen index along with enhanced food and water intake. Columbianadin significantly (P < 0.001) suppressed the level of lactate dehydrogenase (LDH), myeloperoxidase (MPO) and altered the level of oxidative stress parameters such as catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), malonaldehyde (MDA), nitric oxide (NO), SA; cytokines level such as interleukin (IL)-1, 1β, 6, 10, 17, 18, TNF-α; inflammatory parameters viz., cyclooxygenase-2 (COX-2), prostaglandin (PGE), inducible nitric oxide synthetase (iNOS), nuclear factor kappa B (NF-κB), transforming growth factor (TGF-β); apoptosis parameters include Bax, Bcl-2, Bcl-2/Bax ratio, caspase-1 and A-caspase-3 activity, respectively. Columbianadin significantly altered the mRNA expression of IFN-γ, IL-6, IL-1β, IL-8, TNF-α, NF-κB, TLR4, Bcl-2, caspase-9, Bax, p38, ASC, MCP-1, ZO-1, and Ocln. While this study focused on COX-2 modulation as a marker of inflammatory response, no direct measurements or inferences were made regarding leukotriene activity, which involves a separate lipoxygenase pathway.
Columbianadin exhibited the protective effect against DSS-induced UC via alteration of HO-1/Nrf2 and TLR4-NF-κB signaling pathway.
溃疡性结肠炎（UC）是一种重要的炎症性肠病（IBD），通常由肠道慢性炎症引起。报告表明，抗炎药物在UC的防治中起关键作用。最近的研究表明，哥伦比亚苷通过调节HO-1/Nrf2和TLR4-NF-κB信号通路，对葡聚糖硫酸钠（DSS）诱导的大鼠UC具有保护作用。
本研究使用瑞士Wistar大鼠，用2% DSS诱导UC。治疗方案包括给大鼠口服哥伦比亚苷（5、10和15 mg/kg）和柳氮磺胺吡啶。评估体重、脾脏指数、疾病活动指数（DAI）、结肠长度、食物和水摄入量。此外，还测定了抗氧化、细胞因子、炎症和凋亡参数。还对mRNA表达水平进行了定量分析。
哥伦比亚苷治疗显著（P < 0.001）提高了体重并抑制了DAI。哥伦比亚苷显著（P < 0.001）增加了结肠长度，降低了脾脏指数，同时增加了食物和水的摄入量。哥伦比亚苷显著（P < 0.001）抑制了乳酸脱氢酶（LDH）、髓过氧化物酶（MPO）水平，并改变了氧化应激参数如过氧化氢酶（CAT）、超氧化物歧化酶（SOD）、谷胱甘肽还原酶（GR）、谷胱甘肽过氧化物酶（GPx）、丙二醛（MDA）、一氧化氮（NO）、SA的水平；细胞因子水平如白细胞介素（IL）-1、1β、6、10、17、18、肿瘤坏死因子-α（TNF-α）；炎症参数即环氧合酶-2（COX-2）、前列腺素（PGE）、诱导型一氧化氮合酶（iNOS）、核因子κB（NF-κB）、转化生长因子（TGF-β）；凋亡参数分别包括Bax、Bcl-2、Bcl-2/Bax比值、半胱天冬酶-1和活化的半胱天冬酶-3活性。哥伦比亚苷显著改变了IFN-γ、IL-6、IL-1β、IL-8、TNF-α、NF-κB、TLR4、Bcl-2、半胱天冬酶-9、Bax、p38、ASC、MCP-1、ZO-1和闭合蛋白（Ocln）的mRNA表达。虽然本研究将COX-2调节作为炎症反应的标志物，但未对白三烯活性进行直接测量或推断，白三烯活性涉及一条单独的脂氧合酶途径。
哥伦比亚苷通过改变HO-1/Nrf2和TLR4-NF-κB信号通路，对DSS诱导的UC具有保护作用。
