miR166u-enriched Polygonatum sibiricum exosome-like nanoparticles alleviate colitis by improving intestinal barrier through the TLR4/ AKT pathway

文献类型： 外文期刊

第一作者： Wei, Chaozhi

作者： Wei, Chaozhi;Chen, Yue;Chen, Jiali;Cheng, Jintao;Pan, Chunqiang;Wei, You;Liu, Tao;Jin, Yuanxiang;Yang, Guiling;Wei, Chaozhi;Chen, Jiali;Pan, Chunqiang;Wei, You;Jin, Yuanxiang;Cao, Feiying;Yang, Guiling

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关键词： Polygonatum sibiricum; Exosome-like nanovesicles; Colitis; Intestinal barrier; miRNA

期刊名称：INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES （ 影响因子：8.5； 五年影响因子：8.7 ）

ISSN： 0141-8130

年卷期： 2025 年 318 卷

页码：

收录情况： SCI

摘要： Polygonatum sibiricum-derived exosome-like nanoparticles (PSELNs) have emerged as promising natural nanocarriers for modulating intestinal inflammation, yet their therapeutic mechanisms remain unclear. This study evaluates the protective effects and underlying pathways of PSELNs against dextran sulfate sodium (DSS)induced colitis in mice. PSELNs were isolated from P. sibiricum rhizomes using tangential flow filtration and characterized via transmission electron microscopy, nanoparticle tracking analysis, and miRNA sequencing. Oral administration of PSELNs demonstrated notable gastrointestinal stability and targeted colon delivery in vivo. In the DSS-induced colitis model, PSELNs significantly ameliorated disease severity, restored colonic histological architecture, and enhanced intestinal barrier integrity by upregulating tight junction proteins (ZO-1, Occludin) and mucin (MUC2) expression. PSELNs also attenuated inflammation by reducing TNF-alpha and LPS levels and downregulating TLR4/AKT/NF-kappa B signaling, as confirmed byRT- qPCR and Western blot analyses. 16S rRNA sequencing and untargeted metabolomics revealed that PSELNs reshaped gut microbiota composition-particularly increasing Akkermansia-and modulated amino acid and steroid metabolism. Mechanistically, the highly abundant miR166u in PSELNs directly targeted CD11c, thereby suppressing downstream pro-inflammatory signaling. These findings highlight PSELNs as a novel dietary-derived therapeutic strategy to alleviate colitis via gut barrier restoration, immune modulation, and microbiota-metabolite interactions.

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