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含有鞣花酸的石榴衍生外泌体样纳米囊泡可减轻非酒精性脂肪性肝炎相关肝纤维化中的肠渗漏和肝损伤。

Pomegranate-Derived Exosome-Like Nanovesicles Containing Ellagic Acid Alleviate Gut Leakage and Liver Injury in MASLD.

作者信息

Kim Ji-Su, Song Byoung-Joon, Cho Young-Eun

机构信息

Department of Food and Nutrition Andong National University Andong South Korea.

Section of Molecular Pharmacology and Toxicology National Institute on Alcohol Abuse and Alcoholism Bethesda Maryland USA.

出版信息

Food Sci Nutr. 2025 Apr 10;13(4):e70088. doi: 10.1002/fsn3.70088. eCollection 2025 Apr.

DOI:10.1002/fsn3.70088
PMID:40212474
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11982932/
Abstract

Exosome-like nanovesicles derived from plants (PENs) harbor a spectrum of bioactive compounds, including proteins, lipids, nucleic acids (such as miRNAs and mRNAs), offering therapeutic advantages for a variety of diseases. This investigation assesses the utility of pomegranate-derived exosome-like nanovesicles (PNVs) in both preventing and treating complications such as liver damage and increased intestinal permeability found in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Utilizing Transmission Electron Microscopy (TEM) and Nanoparticle Tracking Analysis (NTA), we successfully isolated PNVs and characterized their structural properties. Upon administration in a live model, these nanovesicles were efficiently distributed to critical organs, including the liver and intestines, demonstrating biocompatibility by avoiding toxic effects. Remarkably, these vesicles were enriched with ellagic acid, known for its strong antioxidant capabilities. In a controlled MASLD mouse study, treatment with PNVs significantly lowered serum endotoxin levels, reinforced intestinal barrier functions, and altered the gut microbiota profile favorably. Furthermore, the application of PNVs reduced oxidative stress and the presence of fibrosis markers in the liver to normal levels. These results indicate that PNVs could be a viable option for addressing MASLD, enhancing intestinal integrity, reducing liver injury, and diminishing fibrosis through the modulation of the gut-liver axis.

摘要

源自植物的外泌体样纳米囊泡(PENs)含有一系列生物活性化合物,包括蛋白质、脂质、核酸(如微小RNA和信使RNA),对多种疾病具有治疗优势。本研究评估了石榴衍生的外泌体样纳米囊泡(PNVs)在预防和治疗代谢功能障碍相关脂肪性肝病(MASLD)中出现的肝脏损伤和肠道通透性增加等并发症方面的效用。利用透射电子显微镜(TEM)和纳米颗粒跟踪分析(NTA),我们成功分离出PNVs并表征了它们的结构特性。在活体模型中给药后,这些纳米囊泡有效地分布到包括肝脏和肠道在内的关键器官,通过避免毒性作用证明了生物相容性。值得注意的是,这些囊泡富含以强大抗氧化能力著称的鞣花酸。在一项对照的MASLD小鼠研究中,用PNVs治疗显著降低了血清内毒素水平,增强了肠道屏障功能,并有利地改变了肠道微生物群谱。此外,PNVs的应用将肝脏中的氧化应激和纤维化标志物水平降低至正常水平。这些结果表明,PNVs可能是通过调节肠-肝轴来解决MASLD、增强肠道完整性、减少肝脏损伤和减轻纤维化的可行选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d92c/11982932/ead9fe1a4bfa/FSN3-13-e70088-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d92c/11982932/a0a54913ea9f/FSN3-13-e70088-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d92c/11982932/0132ed3272a9/FSN3-13-e70088-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d92c/11982932/4e8e05acb300/FSN3-13-e70088-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d92c/11982932/268a0e42ed98/FSN3-13-e70088-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d92c/11982932/ae9ed804275b/FSN3-13-e70088-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d92c/11982932/ead9fe1a4bfa/FSN3-13-e70088-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d92c/11982932/a0a54913ea9f/FSN3-13-e70088-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d92c/11982932/0132ed3272a9/FSN3-13-e70088-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d92c/11982932/4e8e05acb300/FSN3-13-e70088-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d92c/11982932/268a0e42ed98/FSN3-13-e70088-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d92c/11982932/ae9ed804275b/FSN3-13-e70088-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d92c/11982932/ead9fe1a4bfa/FSN3-13-e70088-g003.jpg

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