ABSTRACT: Ziziphus jujuba Mill., documented in Shennong Bencao Jing, demonstrates medicinal agents and enhanced longevity through sustained consumption. Yet their specific medicinal components and mechanisms of action require further exploration. In light of increasing radiation exposure from medical procedures, environmental hazards, and aerospace activities, this study aims to elucidate the radioprotective mechanisms of jujube aqueous extract (JAE). JAE effects were tested in UVC-irradiated A549 and HaCaT cells and x-ray-exposed mice. Cell viability, oxidative stress markers, hematological and histopathological parameters, and proteomic profiles were analyzed. Key apoptotic proteins and the core bioactive compound were identified. JAE demonstrated antioxidant activity in vitro, effectively scavenging free radicals (p < 0.01). In C57BL/6 mice subjected to 6 Gy x-ray irradiation, JAE significantly alleviated lymphocytopenia (p < 0.05, 74.31% alleviation), attenuated lung damage, and mitigated oxidative stress by enhancing SOD (41.70% increase) and CAT (10.43% increase) activities while suppressing MDA levels (13.59% decrease, all p < 0.05). Proteomic profiling further identified 58 apoptosis-associated proteins, demonstrating modulation of apoptotic pathways through upregulation of anti-apoptotic Bcl-XL and downregulation of pro-apoptotic Bax, Bik, and cytochrome c (p < 0.05). In A549 and HaCaT cells, JAE enhanced viability (p < 0.05, 37.06% and 14.08% increase), reduced ROS, and restored redox homeostasis (p < 0.05). Arbutin was identified as a key bioactive compound in JAE, conferring radioprotection by anti-apoptotic, anti-inflammatory, and stabilizing mitochondrial function. By combining proteomics with functional validation, this study reveals JAE's radioprotective mechanism via apoptosis modulation and antioxidant enhancement, highlighting arbutin as a key mediator. These findings provide a pharmacological foundation for developing jujube-based adjuvants in radiation oncology and aerospace medicine.
