Ulcerative colitis (UC), as a most common inflammatory bowel disease (IBD), has become a global public health concern. Exploring novel method of treating UC is urgent and necessary. Recently, nanozyme with excellent antioxidant properties may be one useful therapeutic strategy. In this study, a two-dimensional transition metal chalcogenide (TMCs) nano flake and polyethylene glycol (PEG) modified Mo₃Se₄ nano flakes (PMNFs) was synthesized, which had multi-enzyme activity, including peroxidase, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT). The inhibition effect of PMNFs on sodium dextran sulfate (DSS)-induced colitis was explored. UC was effectively inhibited by PMNFs in this work. PMNFs significantly reduced disease activity index (DAI) score, including weight loss, colon shorten and histopathological abnormalities. The possible mechanism of PMNFs-attenuated colitis was investigated. The results showed that PMNFs reversed DSS-induced oxidative damage, and the antioxidant pathway Nrf2-keap1 signal was activated by PMNFs. Moreover, PMNFs suppressed the expression of pro-inflammatory factors including IL-1β, TNF-α, IFN-β and IL-6 via the inactivation of TLR4/NF-κB pathway in DSS-induced colitis and LPS-treated macrophage. Furthermore, PMNFs treatment prevented the reduction of tight junction proteins (ZO-1, occludin, and claudin-1) and mucin-2 (MUC-2) as well as the up-regulation of epithelial apoptosis caused by DSS. These findings demonstrate that the PMNFs against DSS-induced colitis due to its prevention on oxidative damage, inflammation, and intestine barrier breakdown. Thus, PMNFs have a potential application in the treatment of various oxidative stress or inflammation-related diseases.

溃疡性结肠炎（UC）作为最常见的炎症性肠病（IBD），已成为全球公共卫生问题。探索治疗UC的新方法迫在眉睫。最近，具有优异抗氧化特性的纳米酶可能是一种有用的治疗策略。在这项研究中，二维过渡金属硫属化物 (TMCs) 纳米片和聚乙二醇 (PEG) 改性 Mo ₃ Se ₄合成了具有多种酶活性的纳米薄片（PMNFs），包括过氧化物酶、谷胱甘肽过氧化物酶（GPx）、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）。探讨了 PMNFs 对葡聚糖硫酸钠 (DSS) 诱导的结肠炎的抑制作用。在这项工作中，PMNFs 有效地抑制了 UC。PMNFs 显着降低了疾病活动指数 (DAI) 评分，包括体重减轻、结肠缩短和组织病理学异常。研究了 PMNFs 减毒结肠炎的可能机制。结果表明，PMNFs逆转DSS诱导的氧化损伤，抗氧化途径Nrf2-keap1信号被PMNFs激活。此外，PMNFs 抑制促炎因子的表达，包括 IL-1β、TNF-α、IFN-β 和 IL-6 通过 DSS 诱导的结肠炎和 LPS 处理的巨噬细胞中 TLR4/NF-κB 通路的失活。此外，PMNFs 治疗阻止了紧密连接蛋白（ZO-1、occludin 和 claudin-1）和粘蛋白 2（MUC-2）的减少以及 DSS 引起的上皮细胞凋亡的上调。这些发现表明，PMNFs 可以对抗 DSS 诱导的结肠炎，因为它可以预防氧化损伤、炎症和肠道屏障破坏。因此，PMNFs 在治疗各种氧化应激或炎症相关疾病方面具有潜在的应用价值。这些发现表明，PMNFs 可以对抗 DSS 诱导的结肠炎，因为它可以预防氧化损伤、炎症和肠道屏障破坏。因此，PMNFs 在治疗各种氧化应激或炎症相关疾病方面具有潜在的应用价值。这些发现表明，PMNFs 可以对抗 DSS 诱导的结肠炎，因为它可以预防氧化损伤、炎症和肠道屏障破坏。因此，PMNFs 在治疗各种氧化应激或炎症相关疾病方面具有潜在的应用价值。