Aug 2026· Antioxidants· Vol 15, pp. 1048· 0 citations· 44 references
Medicine
TL;DR
It is shown that CDP dose-dependently restores splenic mass, rescues white-pulp atrophy, and suppresses megakaryocytic hyperplasia, and collectively mitigates CTX-induced splenic injury primarily through coupled redox restoration and transcriptional-level immune modulation.
Abstract
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.
BXGG partially reversed CTX-associated reductions in body weight, thymus and spleen indices and partially restored serum interleukin-2, interleukin-4 (IL-4), and interferon-gamma (IFN-γ) levels, and white blood cell, lymphocyte, platelet, and reticulocyte counts.
Inonotus hispidus polysaccharides (IHP) from this edible medicinal fungus exhibit notable immunological benefits, yet fraction specific effects on host immunity and the gut microbiota remain unclear. This study investigated the differential bioactivities of three graded ethanol-precipitated fractions (IHP-65, IHP-75, and IHP-85) in a cyclophosphamide (CTX)-induced immunosuppressed mouse model. Structural characterization revealed that IHP-65 was a 1098 kDa complex heteropolysaccharide, whereas IHP-85 comprised a highly uniform 19.7 kDa glucan core. Following oral administration, all fractions mitigated CTX induced weight loss, significantly increased spleen and thymus indices, and restored IL-2 and TNF-α toward normal levels. Efficacy was strictly fraction dependent, with the low molecular weight IHP-85 consistently outperforming IHP-75 and IHP-65. Microbiota analysis showed a marked reversal of CTX induced dysbiosis, significantly expanding Bacteroidetes and Firmicutes while suppressing Proteobacteria. At the genus level, Alistipes and Lactobacillus rose and Alloprevotella declined, collectively tracking a recovery trajectory toward the normal control community. These findings demonstrate distinct structure activity relationships among IHP fractions, establishing a clear mechanistic framework for utilizing specific low molecular weight glucans as functional food ingredients to modulate host health via the gut immune axis. PRACTICAL APPLICATIONS: This research demonstrates that graded ethanol precipitation is an effective method for isolating high-activity polysaccharides from Inonotus hispidus. Specifically, the fraction precipitated at high ethanol concentrations shows superior potential for boosting immunity and regulating gut health. These findings provide a scientific basis for food manufacturers to optimize processing techniques and develop effective, natural functional food ingredients targeted at immune support.
Ao Jing, Xiaofan Sun, Shuqing Zhou et al.· Journal of Food Science· 0 citations
Immune homeostasis serves as the foundation for disease prevention and the cornerstone for ensuring human health. The effects of Abelmoschus manihot (L.) leaf flavonoids (AMLF) on restoring immune function were investigated in a cyclophosphamide (CTX)-induced immunosuppressed mouse model. The underlying repair mechanisms were explored by an integrative analysis of intestinal microbiomics and serum metabolomics. The results demonstrated that AMLF markedly elevated the spleen and thymus indices, promoted the proliferation of splenic lymphocytes in the presence of concanavalin A (ConA) or lipopolysaccharide (LPS) and CD4+ and CD8+ T lymphocyte subsets, and concomitantly enhanced the serum levels of key immunomodulatory cytokines, including interleukin-1β (IL-1β), interleukin-2 (IL-2), and tumor necrosis factor-α (TNF-α), and the antibody immunoglobulin G (IgG). In addition, AMLF treatment effectively mitigated CTX-induced histopathological injuries to immune organs and the colon. AMLF were also found to protect the liver by regulating antioxidant enzyme activities. Furthermore, AMLF markedly improved the intestinal microbial community structure, promoted the enrichment of beneficial bacteria (Lactobacillaceae and Prevotellaceae), inhibited pathogenic bacteria (Muribaculaceae and Desulfovibrionaceae), and increased the content of short-chain fatty acids (SCFAs). Serum metabolomic analysis showed that AMLF upregulated the levels of leukotrienes, S-(PGA1)-glutathione and prostaglandin E2. Correlation analysis identified g_Alistipes, g_norank_f_Muribaculaceae, and g_Kurthia as potential microbiota strongly associated with the restoration of immune and metabolic homeostasis after AMLF treatment. These findings support the dual potential of AMLF in functional foods and as immunomodulatory adjuvants.
Findings indicate that LDSOL ameliorates cyclophosphamide-induced immunosuppression in mice and suggest that metabolic remodeling and gut microbiota alterations may be associated with its immunomodulatory effects.
Xinyu Chen, Guozhao Li, Zhiwei Wang et al.· Microbial Pathogenesis· 0 citations
In vitro, LJFE dose-dependently activated the Keap1/Nrf2/HO-1 signalling axis and suppressed excessive NO release in LPS-challenged macrophages, and support the potential of LJFE for further development as an immune-enhancing functional food ingredient.
Mei Peng, Xiong Pan, Guanping Yao et al.· Frontiers in Pharmacology· 0 citations
Background: Cyclophosphamide (CTX)-induced immunosuppression involves systemic toxicity, splenic atrophy, and broad transcriptomic disruption. Icariin (ICA) has immunomodulatory activity, but the systems-level features associated with splenic recovery remain incompletely defined. Methods and Results: Male mice were assigned to control, CTX, and CTX plus ICA (20, 40, or 80 mg/kg) groups. Phenotypic measurements were integrated with splenic RNA sequencing, differential expression analysis, targeted gene-set analysis, and weighted gene co-expression network analysis (WGCNA). ICA produced dose-associated improvement in spleen index and body weight trajectory, with the most consistent phenotypic response at 80 mg/kg. Overall transcriptomic separation was supported by permutational multivariate analysis of variance (PERMANOVA) (F = 17.18, R2 = 0.873, p < 0.001). WGCNA identified a recovery-associated turquoise module; Myb was assigned to this module, whereas Gata1 belonged to a distinct royalblue module. Complement and chemokine gene sets provided the strongest targeted enrichment evidence, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) confirmed dose-associated changes in selected innate immune transcripts. Marker-based lineage signatures indicated non-uniform recovery, including persistent depression of the B-cell signature. Conclusion: ICA-associated phenotypic recovery coincided with partial, non-uniform remodeling of splenic transcriptional programs. The Myb- and Gata1-associated findings are hypothesis-generating co-expression signals and do not establish transcription-factor binding or causality.
Nan Li, Shao-Chen Jiang, Zhe Ding et al.· Immuno· 0 citations
