Vacuum-facilitated association of salidroside with Akkermansia muciniphila enhances protection against acute high-altitude illness-associated oxidative and inflammatory stress

Background Acute high-altitude illness (AHAI) involves hypoxia-driven oxidative and inflammatory stress, while salidroside (SAL) is limited by short oral persistence. Methods SAL@AKK, a formulation generated through vacuum-facilitated association of salidroside with Akkermansia muciniphila (AKK), was prepared and evaluated for in vitro release behavior and prophylactic efficacy in zebrafish exposed to simulated altitude (6000 m, 2 h). Behavioral performance, oxidative stress, inflammatory cytokines, and gill histopathology were assessed. Results SAL@AKK showed gradual SAL release in simulated intestinal fluid in vitro and, compared with AHAI controls, improved locomotor/exploratory behavior and reduced freezing. It lowered reactive oxygen species (ROS) and malondialdehyde (MDA), restored glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD), decreased tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β), and reduced gill inflammatory infiltration. Across outcomes, SAL@AKK showed stronger overall effects than SAL or AKK alone. Correlation and PCA analyses suggested coordinated changes among behavioral, redox, and inflammatory parameters. Conclusion Vacuum-facilitated association with AKK enhanced the functional efficacy of SAL against AHAI-associated oxidative and inflammatory stress.