Targeting SIRT1 via Exosomes Derived From Oleuropein-Treated Cells: A Novel Approach to Rejuvenation Skin Through miRNA Modulation.

() 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.