口服艾叶衍生的外泌体样纳米囊泡可通过调节肠道微生物来改善溃疡性结肠炎。

IF 6.7 1区 医学 Q1 CHEMISTRY, MEDICINAL
Phytomedicine Pub Date : 2025-02-01 Epub Date: 2025-01-04 DOI:10.1016/j.phymed.2025.156376
Yishu Li, Su Shao, Yuanhao Zhou, Yuanyuan Wang, Wenjie Zheng, Huanying Wang, Meixia Wang, Ketao Jin, Hai Zou, Xiaozhou Mou
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引用次数: 0

摘要

背景:溃疡性结肠炎(UC)是一种以肠道屏障功能障碍为特征的炎症性疾病,由于其毒性和不良反应通常与常规治疗相关,因此面临着重大挑战。需要更安全、更有效的治疗策略。目的:探讨艾叶外泌体样纳米囊泡(FAELNs)治疗UC的作用机制,为治疗溃疡性结肠炎提供更安全、更有效的手段。方法:采用HT-29人结直肠癌细胞建立小鼠急性UC的体内模型和体外炎症模型。为了评估FAELNs对UC的治疗效果,我们采用了多种指标,包括小鼠体重和疾病活动指数(DAI)的变化,以及结肠长度的测量。采用ELISA法检测小鼠血清中髓过氧化物、白细胞介素(IL-1β)、IL-6、肿瘤坏死因子- α、单核细胞趋化蛋白-1、干扰素- γ的浓度。免疫组织化学、苏木精染色、伊红染色、艾莉辛蓝染色。采用活性氧探针、二乙酰二氯荧光素和流式细胞术检测HT-29细胞对氧化应激的影响。Western blotting检测FAELNs处理HT-29细胞中Bax和Bcl-2的表达水平。采用荧光定量PCR检测FAELNs对IL-6和IL-1β的影响。通过α多样性和β多样性分析、主成分分析、物种分布和功能预测验证了FAELNs的作用。对于faeln的microRNA测序,进行了基因本体和京都基因与基因组百科全书的分析。为了检测faeln的代谢和脂质组,我们鉴定了这些成分,并构建了药理学网络,以探索其相关机制和疾病。结果:FAELNs可有效缓解动物模型葡聚糖硫酸钠所致UC的发病机制,恢复肠道屏障的完整性,逆转肠道菌群失衡。结论:我们的研究结果证明了faeln在UC治疗中的治疗潜力,强调了其大规模生产的可扩展性和鼓励临床转化的前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Oral administration of Folium Artemisiae Argyi-derived exosome-like nanovesicles can improve ulcerative colitis by regulating intestinal microorganisms.

Background: Ulcerative colitis (UC), an inflammatory disease characterized by intestinal barrier dysfunction, poses significant challenges because of the toxicity and adverse effects commonly associated with conventional therapies. Safer and more efficacious treatment strategies are needed.

Purpose: The purpose of this study was to treat UC with Folium Artemisiae Argyi exosome-like nanovesicles (FAELNs) and to explore its related mechanism to provide a safer and more effective means for the treatment of ulcerative colitis.

Methods: We established an in vivo model of acute UC in mice and an in vitro inflammatory model using HT-29 human colorectal cancer cells. To evaluate the therapeutic effect of FAELNs on UC, we adopted various proxies, including changes in body weight and disease activity index (DAI) of mice, and measurement of colon length. The concentrations of myeloperoxide, interleukin (IL-1β), IL-6, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and interferon-gamma in sera of mice were detected by ELISA. Immunohistochemistry, hematoxylin and eosin staining, and Alyssin blue staining were performed. The effect of HT-29 cells on oxidative stress was detected using an active oxygen probe, diacetyldichlorofluorescein, and flow cytometry. Western blotting was performed to detect the expression levels of Bax and Bcl-2 in HT-29 cells treated with FAELNs. The effects of FAELNs on IL-6 and IL-1β were detected by fluorescence quantitative PCR. Fecal 16S bacteria were detected, and the role of FAELNs was verified by α diversity and β diversity analyses, principal component analysis, species distribution, and function prediction. For microRNA sequencing of FAELNs, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed. To detect the metabolic and lipid groups of FAELNs, the components were identified and a pharmacological network was constructed to explore the related mechanisms and diseases.

Results: FAELNs effectively alleviated the pathogenesis of UC induced by dextran sodium sulfate in animal models, restoring the integrity of the intestinal barrier and reversing an imbalance of the intestinal microbiota.

Conclusion: Our findings demonstrate the therapeutic potential of FAELNs in UC management, highlighting their scalability for mass production and encouraging prospects for clinical transformation.

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来源期刊
Phytomedicine
Phytomedicine 医学-药学
CiteScore
10.30
自引率
5.10%
发文量
670
审稿时长
91 days
期刊介绍: Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.
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