Zhao Yinyin, Jiang Binyuan, Zuo Shengnan
Ningbo Institute of Innovation for Combined Medicine and Engineering (NIIME), The Affiliated LiHuiLi Hospital of Ningbo University, Ningbo, People's Republic of China.
Medical Research Center of the Affiliated Changsha Central Hospital of Hengyang Medical School, University of South China, Changsha, People's Republic of China.
J Inflamm Res. 2025 Jan 31;18:1447-1458. doi: 10.2147/JIR.S500722. eCollection 2025.
Cucurbitacins have demonstrated anti-inflammatory effects and show promise for inflammatory bowel diseases. However, the underlying mechanisms by which cucurbitacins affect colitis remain largely unknown.
In this study, we investigated the impact of cucurbitacin IIa on dextran sulfate sodium (DSS)-induced colitis in rats and the alterations in intestinal extracellular vesicles (EVs). EVs were isolated and characterized, followed by analysis of the small RNAs and proteins encapsulated within them using small RNA sequencing and proteomics, respectively.
Our results revealed that cucurbitacin IIa alleviated colitis symptoms in DSS-treated rats, along with changes in the morphology and composition of intestinal EVs. Notably, EVs from cucurbitacin IIa-treated rats also mitigated colitis symptoms in DSS-treated rats. Further analysis showed that cucurbitacin IIa modified the protein profiles and microRNA composition of EVs extracted from the feces of colitis rats. Specifically, microRNA-30b-5p, significantly increased by cucurbitacin IIa, was found to alleviate colitis symptoms in DSS-treated rats. In conclusion, cucurbitacin IIa appears to alleviate colitis by promoting the release of microRNA-30b-5p from host-derived extracellular vesicles.
These findings enhance our understanding of cucurbitacin IIa's effects on intestinal health and offer potential new therapeutic targets for inflammatory bowel disease treatment.
葫芦素已显示出抗炎作用，并对炎症性肠病具有治疗潜力。然而，葫芦素影响结肠炎的潜在机制仍不清楚。
在本研究中，我们调查了葫芦素IIa对葡聚糖硫酸钠（DSS）诱导的大鼠结肠炎的影响以及肠道细胞外囊泡（EVs）的变化。分离并鉴定了EVs，随后分别使用小RNA测序和蛋白质组学分析了其中包裹的小RNA和蛋白质。
我们的结果表明，葫芦素IIa减轻了DSS处理大鼠的结肠炎症状，同时肠道EVs的形态和组成也发生了变化。值得注意的是，来自葫芦素IIa处理大鼠的EVs也减轻了DSS处理大鼠的结肠炎症状。进一步分析表明，葫芦素IIa改变了从结肠炎大鼠粪便中提取的EVs的蛋白质谱和微小RNA组成。具体而言，葫芦素IIa显著增加的微小RNA-30b-5p被发现可减轻DSS处理大鼠的结肠炎症状。总之，葫芦素IIa似乎通过促进宿主来源的细胞外囊泡释放微小RNA-30b-5p来减轻结肠炎。
这些发现加深了我们对葫芦素IIa对肠道健康影响的理解，并为炎症性肠病的治疗提供了潜在的新治疗靶点。
