Transcriptomic Analysis Reveals the Protective Effects of Eucommia ulmoides Leaf Extract Against D-Galactose-Induced Senescence in Avian Intestinal Epithelial Cells

Eucommia ulmoides leaf extract (ELE) boasts a high concentration of bioactive components including flavonoids, chlorogenic acid, and polysaccharides. It exhibits multiple biological functions, including antioxidant, anti-inflammatory, and gut microbiota-modulating properties, showing great potential in enhancing immunity, maintaining intestinal health, and delaying cellular senescence. This study investigated the protective effects and underlying mechanisms of ELE against D-galactose-induced senescence in chick embryo primary intestinal epithelial cells (IECs). Using an in vitro model (200 mmol/L D-galactose), we found that 100 µg/mL ELE pretreatment significantly preserved cell viability, mitigated apoptosis, and delayed cellular senescence, as evidenced by cytological and biochemical assays. Furthermore, RNA-seq transcriptomic analysis identified seven key differentially expressed genes (DEGs) mediating these anti-aging effects. Mechanistic investigations revealed that ELE modulates ATP6V0D2 and NCF2 to activate autophagy signaling pathways. This ELE-induced promotion of autophagy effectively suppresses inflammatory responses in IECs, thereby delaying senescence progression. These findings elucidate the molecular mechanisms by which ELE antagonizes intestinal cellular senescence, providing a solid theoretical foundation for its development as a functional anti-aging additive in the food industry.