Houttuynia cordata-Derived Exosome-Like Nanoparticles Mitigate Colitis in Mice via Inhibition of the NLRP3 Signaling Pathway and Modulation of the Gut Microbiota

作者：Jianhong Li, Jing Xu, Chen Huang, Jin-Xia Hu, Haoming Xu, Xue Guo, Yan Zhang, Jun Xu, Yao Peng, Yong Zhang, Min‐zheng Zhu, Youlian Zhou, Yuqiang Nie · 发表于：International Journal of Nanomedicine · 年份：2024 · DOI：10.2147/ijn.s493434 · 被引用次数：49 · 研究领域：Nephrotoxicity and Medicinal Plants、Inflammatory Bowel Disease、Inflammasome and immune disorders

Background: Plant-derived exosome-like nanoparticles (PELNs) have received widespread attention in treating ulcerative colitis (UC). However, the role of Houttuynia cordata -derived exosome-like nanoparticles (HELNs) in UC remains unclear. This study aims to evaluate the efficacy of HELNs in treating colitis in mice and investigate its potential mechanisms. Methods: HELNs were isolated from H. cordata for characterization, and their safety and stability were evaluated. A dextran sulfate sodium (DSS)-induced colitis mouse model was utilized to assess the therapeutic potential of HELNs in UC. In vivo, imaging and flow cytometry were utilized to investigate the targeting effect of HELNs on inflamed colonic sites and their modulation of the immune environment. RNA-seq analysis and molecular docking were performed to identify potential pathways recruited by HELNs. Guided by transcriptomic findings, NLRP3 −/− mice were used in conjunction with Western blotting, qPCR, immunofluorescence, and other techniques to verify that HELNs alleviated DSS-induced colitis by inhibiting NLRP3/NOD-like receptor signaling pathways. Lastly, the impact of HELNs on the gut microbiota was investigated through 16S rRNA sequencing. Results: HELNs significantly reduced the severity of DSS-induced colitis in mice, alleviating colitis symptoms and histopathological damage. Furthermore, HELNs can specifically target inflamed colon tissue, regulate the immune environment, and decrease inflammation. RNA-seq an...