College of Veterinary Medicine, Jilin University, No. 5333 Xi'an Road, Changchun, Jilin, 130062, China.
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Jilin University, No. 5333 Xi'an Road, Changchun, Jilin, 130062, China.
J Transl Med. 2024 May 21;22(1):488. doi: 10.1186/s12967-024-05285-6.
Ulcerative colitis (UC) is an idiopathic, chronic inflammatory condition of the colon, characterized by repeated attacks, a lack of effective treatment options, and significant physical and mental health complications for patients. The endoplasmic reticulum (ER) is a vital intracellular organelle in maintaining cellular homeostasis. Endoplasmic reticulum stress (ERS) is induced when the body is exposed to adverse external stimuli. Numerous studies have shown that ERS-induced apoptosis plays a vital role in the pathogenesis of UC. Mogroside V (MV), an active ingredient of Monk fruit, has demonstrated excellent anti-inflammatory and antioxidant effects. In this study, we investigated the therapeutic effects of MV on dextran sulfate sodium (DSS)-induced UC and its potential mechanisms based on ERS. The results showed that MV exerted a protective effect against DSS-induced UC in mice as reflected by reduced DAI scores, increased colon length, reduced histological scores of the colon, and levels of pro-inflammatory cytokines, as well as decreased intestinal permeability. In addition, the expression of ERS pathway including BIP, PERK, eIF2α, ATF4, CHOP, as well as the apoptosis-related protein including Caspase-12, Bcl-2 and Bax, was found to be elevated in UC. However, MV treatment significantly inhibited the UC and reversed the expression of inflammation signaling pathway including ERS and ERS-induced apoptosis. Additionally, the addition of tunicamycin (Tm), an ERS activator, significantly weakened the therapeutic effect of MV on UC in mice. These findings suggest that MV may be a therapeutic agent for the treatment of DSS-induced UC by inhibiting the activation of the ERS-apoptosis pathway, and may provide a novel avenue for the treatment of UC.
溃疡性结肠炎（UC）是一种特发性、慢性炎症性结肠疾病，其特征为反复发作、缺乏有效治疗方案，以及给患者带来显著的身心健康并发症。内质网（ER）是维持细胞内稳态的重要细胞器。当机体暴露于不利的外界刺激时，会诱导内质网应激（ERS）。大量研究表明，ERS 诱导的细胞凋亡在 UC 的发病机制中起着至关重要的作用。罗汉果苷 V（MV）是罗汉果的一种活性成分，具有优异的抗炎和抗氧化作用。在本研究中，我们基于 ERS 探讨了 MV 对葡聚糖硫酸钠（DSS）诱导的 UC 的治疗作用及其潜在机制。结果表明，MV 通过降低 DAI 评分、增加结肠长度、降低结肠组织学评分以及降低促炎细胞因子水平和肠道通透性，对 DSS 诱导的 UC 小鼠发挥了保护作用。此外，UC 中 ERS 通路包括 BIP、PERK、eIF2α、ATF4、CHOP 以及凋亡相关蛋白包括 Caspase-12、Bcl-2 和 Bax 的表达升高，而 MV 治疗显著抑制了 UC 并逆转了包括 ERS 和 ERS 诱导的细胞凋亡在内的炎症信号通路的表达。此外，添加 ERS 激活剂衣霉素（Tm）显著削弱了 MV 对 UC 小鼠的治疗作用。这些发现表明，MV 可能通过抑制 ERS-细胞凋亡通路的激活，成为治疗 DSS 诱导的 UC 的一种治疗药物，并为 UC 的治疗提供了新的途径。
