Sulfated modification enhances the immunomodulatory effect of Cyclocarya paliurus polysaccharide on cyclophosphamide-induced immunosuppressed mice through MyD88-dependent MAPK/NF-κB and PI3K-Akt signaling pathways

The present study investigated the effect of sulfation on the immunomodulatory effect of Cyclocarya paliurus polysaccharide (CP) through a Cyclophosphamide (CTX)-induced immunosuppression mice model. The results showed that sulfated Cyclocarya paliurus polysaccharide (SCP3) had stronger immunomodulatory ability than CP. Administration of SCP3 alleviated immune organ atrophy and restored hematopoiesis in immunosuppressed mice, enhanced splenocyte proliferation, and promoted cytokines and nitric oxide (NO) production in splenocyte supernatants, as well as the number of CD3+, CD4+ and CD8+ T lymphocytes. Meantime, SCP3 significantly improved oxidative stress via increasing the activities of antioxidant enzymes and decreasing the levels of malondialdehyde (MDA) in liver. In addition, SCP3 significantly upregulated the phosphorylation expression of JNK, Erk 1/2, p38 of MAPKs signaling pathway at a dose of 50 mg/kg and accordingly showed increased phosphorylation of Akt, NF-κB (p65), IκB-α, and promoted the degradation of IkB-α. Furthermore, SCP3 significantly increased the expression of the upstream signaling molecule MyD88. All results demonstrated that sulfation can be an effective way to enhance the immunomodulatory effect of polysaccharides. SCP3 has high potential to be a functional food supplement candidate for alleviating chemotherapy drug-induced immunosuppression.