Gao Bowen, Huang Xiaoling, Fu Junlong, Chen Liyuan, Deng Zhichao, Wang Shuhui, Zhu Yuanyuan, Xu Chenxi, Zhang Yujie, Zhang Mingxin, Chen Lina, Cui Manli, Zhang Mingzhen
School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
Department of Gastroenterology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang Uygur Autonomous Region, 830001, China.
J Nanobiotechnology. 2025 Apr 1;23(1):261. doi: 10.1186/s12951-025-03346-6.
Ulcerative colitis (UC) is an inflammatory bowel disease (IBD), accompanied by intense inflammation, oxidative stress, and intestinal microbiota dysbiosis. Current treatments using chemotherapeutic drugs or immunosuppressants have limited effectiveness and side effects. Therefore, the development of safe, effective, and multi-targeting therapies for IBD is of great importance. Momordica charantia exhibits antioxidant, anti-inflammatory, and intestinal microbiota-regulating properties, suggesting that Momordica charantia-derived extracellular vesicles (MCEVs) have the potential for UC management.
We extracted MCEVs using differential centrifugation and density gradient centrifugation. The results showed that MCEVs possessed high purity, even particle size, and excellent stability. In vitro, MCEVs were shown to inhibit macrophage inflammatory responses, scavenge reactive oxygen species (ROS), and protect cells from oxidative damage. Transcriptomics analysis revealed that MCEVs may alleviate mitochondria-dependent apoptosis by safeguarding the integrity of the mitochondrial structure and regulating the expression of apoptosis-related proteins. Furthermore, all components of MCEVs contributed to their pharmacological activity. In vivo, MCEVs had better retention in the inflamed colon and significantly alleviated UC through a comprehensive renovation of the intestinal microenvironment.
These findings suggested that MCEVs own considerable potential as natural nanotherapeutics for UC treatment.
溃疡性结肠炎（UC）是一种炎症性肠病（IBD），伴有强烈炎症、氧化应激和肠道微生物群失调。目前使用化疗药物或免疫抑制剂的治疗效果有限且有副作用。因此，开发安全、有效且多靶点的IBD治疗方法至关重要。苦瓜具有抗氧化、抗炎和调节肠道微生物群的特性，这表明苦瓜来源的细胞外囊泡（MCEVs）具有治疗UC的潜力。
我们采用差速离心和密度梯度离心法提取了MCEVs。结果表明，MCEVs具有高纯度、均匀的粒径和优异的稳定性。在体外，MCEVs被证明可抑制巨噬细胞炎症反应、清除活性氧（ROS）并保护细胞免受氧化损伤。转录组学分析表明，MCEVs可能通过维护线粒体结构的完整性和调节凋亡相关蛋白的表达来减轻线粒体依赖性凋亡。此外，MCEVs的所有成分都对其药理活性有贡献。在体内，MCEVs在炎症结肠中具有更好的滞留性，并通过全面改善肠道微环境显著减轻UC。
这些发现表明，MCEVs作为治疗UC的天然纳米疗法具有巨大潜力。
