DataSheet_5_Huang-Lian-Jie-Du Decoction Ameliorates Acute Ulcerative Colitis in Mice via Regulating NF-κB and Nrf2 Signaling Pathways and Enhancing Intestinal Barrier Function.xlsx

Evidence shows that intestinal inflammation, oxidative stress, and injury of mucosal barrier are closely related to the pathogenesis of ulcerative colitis (UC). Huang-lian-Jie-du Decoction (HLJDD) is a well-known prescription of traditional Chinese medicine with anti-inflammatory and antioxidative activities, which may be used to treat UC. However, its therapeutic effect and mechanism are still unclear. In this study, the UC model of BABL/c mice were established by DSS [3.5% (w/v)], and HLJDD was given orally for treatment at the same time. During the experiment, the clinical symptoms of mice were scored by disease activity index (DAI). Besides, the effects of HLJDD on immune function, oxidative stress, colon NF-κB and Nrf2 signaling pathway, and intestinal mucosal barrier function in UC mice were also investigated. The results showed that HLJDD could alleviate body weight loss and DAI score of UC mice, inhibit colonic shortening and relieve colonic pathological damage, and reduce plasma and colon MPO levels. In addition, HLJDD treatment significantly up-regulated plasma IL-10, down-regulated TNF-α and IL-1β levels, and inhibited the expression of NF-κB p65, p-IκKα/β, and p-IκBα proteins in the colon. Moreover, NO and MDA levels in colon tissues were significantly reduced after HLJDD treatment, while GSH, SOD levels and Nrf2, Keap1 protein expression levels were remarkably elevated. Additionally, HLJDD also protected intestinal mucosa by increasing the secretion of mucin and the expression of ZO-1 and occludin in colonic mucosa. These results indicate that HLJDD could effectively alleviate DSS-induced mice UC by suppressing NF-κB signaling pathway, activating Nrf2 signaling pathway, and enhancing intestinal barrier function.

研究证据表明，肠道炎症、氧化应激与黏膜屏障损伤与溃疡性结肠炎（Ulcerative Colitis, UC）的发病机制密切相关。黄连解毒汤（Huang-lian-Jie-du Decoction, HLJDD）是一类经典的中药方剂，具有抗炎与抗氧化活性，有望用于治疗溃疡性结肠炎，但其具体治疗效果与作用机制仍未明确。本研究采用3.5%（质量体积比，w/v）葡聚糖硫酸钠（Dextran Sulfate Sodium, DSS）构建BABL/c小鼠溃疡性结肠炎模型，并同时通过灌胃给予黄连解毒汤进行干预治疗。实验期间，通过疾病活动指数（Disease Activity Index, DAI）对小鼠的临床症状进行评分。此外，本研究还探究了黄连解毒汤对溃疡性结肠炎小鼠免疫功能、氧化应激、结肠核因子κB（Nuclear Factor Kappa B, NF-κB）及核因子E2相关因子2（Nuclear Factor Erythroid 2-related Factor 2, Nrf2）信号通路，以及肠黏膜屏障功能的影响。研究结果显示，黄连解毒汤可缓解溃疡性结肠炎小鼠的体重减轻与疾病活动指数评分，抑制结肠缩短并减轻结肠病理损伤，同时降低血浆与结肠组织的髓过氧化物酶（Myeloperoxidase, MPO）水平。此外，黄连解毒汤治疗可显著上调血浆白细胞介素-10（Interleukin-10, IL-10）的表达水平，下调肿瘤坏死因子-α（Tumor Necrosis Factor-α, TNF-α）与白细胞介素-1β（Interleukin-1β, IL-1β）的含量，并抑制结肠组织中NF-κB p65、p-IκKα/β以及p-IκBα蛋白的表达。进一步研究发现，黄连解毒汤干预后，结肠组织中的一氧化氮（Nitric Oxide, NO）与丙二醛（Malondialdehyde, MDA）水平显著降低，而谷胱甘肽（Glutathione, GSH）、超氧化物歧化酶（Superoxide Dismutase, SOD）水平以及Nrf2、Kelch样ECH相关蛋白1（Keap1）的蛋白表达量显著升高。此外，黄连解毒汤还可通过增加结肠黏膜黏蛋白的分泌以及紧密连接蛋白ZO-1与闭合蛋白（occludin）的表达，发挥肠黏膜保护作用。上述结果表明，黄连解毒汤可通过抑制NF-κB信号通路、激活Nrf2信号通路以及增强肠黏膜屏障功能，有效缓解DSS诱导的小鼠溃疡性结肠炎。