Preparation of Artemisia argyi-Derived Extracellular Nanovesicles and Their Protective Effects Against Oxidative Stress-Induced Senescence in Endometrial Stromal Cells

Oxidative stress-induced endometrial injury has been shown to contribute to infertility; however, effective strategies that can simultaneously scavenge reactive oxygen species (ROS) and restore mitochondrial and antioxidant homeostasis remain elusive. In this study, we isolated extracellular nanovesicles from <i>Artemisia argyi</i> (A-NVs) and investigated their protective effects on H₂O₂-damaged human endometrial stromal cells (hESCs). We discovered that A-NVs possess a typical lipid bilayer structure and contain a variety of bioactive components. Our metabolomic analysis indicates that A-NVs can be regarded as a "natural drug reservoir", in which flavonoids account for approximately 10.8%. We demonstrate that A-NVs can be efficiently taken up by cells, improve cell viability, reduce intracellular and mitochondrial ROS levels, enhance superoxide dismutase (SOD) activity, upregulate the expression of catalase (<i>CAT</i>), <i>SOD1</i>, and <i>SOD2</i>, and partially restore mitochondrial membrane potential. Mechanistically, A-NVs exert antioxidant effects by activating the SIRT1/PGC-1α/Nrf2 signaling axis. SIRT1 activation further alleviates H₂O₂-induced premature senescence, as evidenced by a 71.8% reduction in SA-β-Gal-positive cells compared with the H₂O₂ group, together with downregulation of p53 and p21 expression. These positive protective effects can be blocked by the SIRT1 inhibitor EX-527, confirming the central role of this pathway. Collectively, our findings demonstrate that A-NVs can maintain redox and mitochondrial homeostasis while inhibiting oxidative stress-related senescence progression, underscoring their application potential in endometrial repair and functional recovery.