Safavizadeh Naeimeh, Noormohammadi Zahra, Zaefizadeh Mohammad, Koshki Kazem Nejati
Department of Biology, Science and Research Branch Islamic Azad University Tehran Iran.
Department of Biology Ardabil Branch, Islamic Azad University Ardabil Iran.
Food Sci Nutr. 2025 Sep 14;13(9):e70964. doi: 10.1002/fsn3.70964. eCollection 2025 Sep.
() plays an important role in skin aging by regulating cellular processes such as oxidative stress response, inflammation modulation, and synthesis. This study aims to examine oleuropein's (OLE) effect on gene expression and to analyze -related miRNAs in exosomes produced from Mesenchymal Stem cells (MSC) and Human Fetal Foreskin Fibroblast 2 (HFFF2) cells, along with these treated exosomes' impact on gene expression and the studied miRNAs in HFFF2 cells to decrease skin aging. A nontoxic concentration (400 μg/mL) of OLE was applied to the MSCs and HFFF2 cells. Then, Gradient Ultracentrifugation extracted their exosomes; cell-derived exosomes were confirmed by DLS assay and western Blot. Exosomes were applied at 50 μg/mL (exosome protein concentration) to HFFF2 cells. The expression of gene and related miRNAs relative to the control group were examined using qRT-PCR. This analysis was conducted on cells OLE-treated for , on exosomes treatment with OLE for miRNAs, and on HFFF2 cells treated with cell-derived exosomes for both and miRNAs. expression was upregulated ( ≤ 0.05) in both OLE and cell-derived exosomes. Also, and were downregulated ( ≤ 0.05), whereas was upregulated ( ≤ 0.05) in exosomes OLE-treated and in HFFF2 cells treated with these exosomes. This study introduces a novel approach to skin rejuvenation by using manipulated exosomes OLE-treated, which enhance expression and suppress related miRNAs. This method potentially offers a more effective and less immunogenic alternative to direct OLE application due to the exosomes' ability to penetrate cells.
（）通过调节细胞过程如氧化应激反应、炎症调节和合成，在皮肤衰老中起重要作用。本研究旨在研究橄榄苦苷（OLE）对基因表达的影响，并分析间充质干细胞（MSC）和人胎儿包皮成纤维细胞2（HFFF2）产生的外泌体中与-相关的微小RNA（miRNA），以及这些经处理的外泌体对HFFF2细胞中基因表达和所研究的miRNA的影响，以减少皮肤衰老。将无毒浓度（400μg/mL）的OLE应用于MSC和HFFF2细胞。然后，通过梯度超速离心提取它们的外泌体；通过动态光散射（DLS）测定和蛋白质免疫印迹法确认细胞来源的外泌体。将外泌体以50μg/mL（外泌体蛋白浓度）应用于HFFF2细胞。使用定量逆转录聚合酶链反应（qRT-PCR）检测相对于对照组的基因和相关miRNA的表达。对用OLE处理的细胞进行、用OLE处理外泌体的miRNA以及用细胞来源的外泌体处理HFFF2细胞的和miRNA进行了该分析。在OLE和细胞来源的外泌体中，表达均上调（≤0.05）。此外，在用OLE处理的外泌体和用这些外泌体处理的HFFF2细胞中，和下调（≤0.05），而上调（≤0.05）。本研究引入了一种通过使用经OLE处理的外泌体来实现皮肤年轻化的新方法，这些外泌体增强表达并抑制相关miRNA。由于外泌体具有穿透细胞的能力，这种方法可能提供一种比直接应用OLE更有效且免疫原性更低的替代方法。
