Cistanche deserticola Polysaccharide Ameliorates Cyclophosphamide-Induced Splenic Immunosuppression in Mice: Integrated Transcriptomic and Proteomic Analyses of Immune Modulation

Cistanche deserticola polysaccharide (CDP) exhibits pleiotropic bioactivities, yet its splenic-protective profile remains incompletely defined. Here, male ICR mice were challenged with cyclophosphamide (CTX) to establish an immunosuppressed model and concurrently treated with CDP. By integrating functional assays, splenic histopathology, and transcriptomic and proteomic analyses, we show that CDP dose-dependently restores splenic mass, rescues white-pulp atrophy, and suppresses megakaryocytic hyperplasia. Functionally, CDP rebalances pro-/anti-inflammatory cytokines, scavenges splenic ROS/MDA, and potentiates GSH-Px/SOD antioxidant capacity versus CTX alone. Multi-omics convergence (3103 DEGs; 1387 DEPs) delineated a CDP-distinctive signature related to innate immune recognition, oxidative stress buffering, and protease/ion-transport modules. Notably, transcriptional enrichment of neutrophil extracellular trap (NET)-associated proxies—synergized with NOD-like receptor/IL-17 signaling—suggests a putative innate-priming mechanism warranting functional validation, rather than confirmed pathway activation. Collectively, CDP mitigates CTX-induced splenic injury primarily through coupled redox restoration and transcriptional-level immune modulation.