Oxidative stress (OS) is a key factor in the generation of various pathophysiological conditions. Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) is a major transcriptional regulator of antioxidant reactions. Heme oxygenase-1 (HO-1), a gene regulated by Nrf2, is one of the most critical cytoprotective molecules. In recent years, Nrf2/HO-1 has received widespread attention as a major regulatory pathway for intracellular defense against oxidative stress. It is considered as a potential target for the treatment of inflammatory bowel disease (IBD). This review highlights the mechanism of action and therapeutic significance of Nrf2/HO-1 in IBD and IBD complications (intestinal fibrosis and colorectal cancer (CRC)), as well as the potential of phytochemicals targeting Nrf2/HO-1 in the treatment of IBD. The results suggest that the therapeutic effects of Nrf2/HO-1 on IBD mainly involve the following aspects: (1) Controlling of oxidative stress to reduce intestinal inflammation and injury; (2) Regulation of intestinal flora to repair the intestinal mucosal barrier; and (3) Prevention of ferroptosis in intestinal epithelial cells. However, due to the complex role of Nrf2/HO-1, a more nuanced understanding of the exact mechanisms involved in Nrf2/HO-1 is the way forward for the treatment of IBD in the future.

中文翻译：

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Nrf2/HO-1 在炎症性肠病中的作用机制和治疗意义


氧化应激（OS）是各种病理生理状况产生的关键因素。核因子红细胞 2 (NF-E2) 相关因子 2 (Nrf2) 是抗氧化反应的主要转录调节因子。血红素加氧酶-1 (HO-1) 是 Nrf2 调控的基因，是最关键的细胞保护分子之一。近年来，Nrf2/HO-1作为细胞内防御氧化应激的主要调控途径受到广泛关注。它被认为是治疗炎症性肠病（IBD）的潜在靶点。本综述重点介绍了 Nrf2/HO-1 在 IBD 和 IBD 并发症（肠纤维化和结直肠癌 (CRC)）中的作用机制和治疗意义，以及靶向 Nrf2/HO-1 的植物化学物质在治疗 IBD 中的潜力。结果提示，Nrf2/HO-1对IBD的治疗作用主要涉及以下几个方面：（1）控制氧化应激，减轻肠道炎症和损伤； (2)调节肠道菌群，修复肠粘膜屏障； (3)预防肠上皮细胞铁死亡。然而，由于 Nrf2/HO-1 的复杂作用，对 Nrf2/HO-1 所涉及的确切机制进行更细致的了解是未来治疗 IBD 的方向。