Suppression of NF-κB signaling by Ganoderma-Rhodiola compound preparation alleviates immune dysregulation in a rat model of simulated microgravity

Abstract

Background The extreme environment of spaceflight facilitates the increased pathogenicity of microorganisms while simultaneously compromising the immune systems of astronauts, thereby escalating the risk of infections and threatening mission safety. Effective countermeasures to bolster immune defenses in space are therefore imperative. Objective: This study investigated the immunomodulatory effects and underlying mechanisms of a Ganoderma-Rhodiola Compound Preparation (GRCP) using a rat model subjected to dual stressors (simulated microgravity and microbial challenge). Methods Fifty-four male SD rats were randomized into six groups: Normal Control (NC), Model Control (MC), Positive Control (PC), and three GRCP dosage groups (Low, Medium, and High). To simulate the space environment, the MC, PC, and GRCP groups underwent 4 weeks of tail suspension (hindlimb unloading) and were orally challenged with high-risk space-associated microorganisms to induce immune dysregulation. Post-intervention, we assessed growth trajectories, delayed-type hypersensitivity (DTH), immune organ indices, splenic histopathology, and a panel of serum and jejunal biomarkers, with a specific focus on inflammatory mediators and the NF-κB subunit (RelA) Results GRCP administration significantly improved the physiological status of the rats, including enhanced appetite and weight gain, with the high-dose group (GRCPH) demonstrating the most pronounced efficacy (P < 0.01 vs. MC). Biochemically, GRCP treatment normalized blood indices and modulated both the DTH response and serum hemolysin levels. Notably, GRCPH restored the splenic microarchitecture and elevated serum albumin levels. Furthermore, GRCPH significantly suppressed the overproduction of serum IgG and IgA, pro-inflammatory cytokines, and jejunal inflammatory factors (IL-6, TNF-α, IL-1β, and RelA). Conclusion These findings suggest that the Ganoderma-Rhodiola formulation can effectively restore immune homeostasis and suppress systemic and mucosal inflammation in simulated spaceflight conditions, likely via the inhibition of the NF-κB/RelA pathway. This study provides a scientific rationale for utilizing traditional herbal compounds as protective strategies for long-duration manned space missions.