Longan Polysaccharide as Adjuvant for Cyclophosphamide-Induced Side Effects in Murine Model

Identifying effective adjuvants to prevent and alleviate the adverse effects of chemotherapy remains a critical challenge in cancer therapy. This study investigated the protective effects of longan polysaccharide (LP) against cyclophosphamide-induced immunosuppression and oxidative stress in mice. Our findings revealed that LP administration significantly improved systemic immune function, as evidenced by marked increases in serum immunoglobulin levels (IgG2a: 1.82-fold, IgG2b: 1.46-fold, IgM: 1.26-fold, and IgG1: 1.22-fold) and key cytokines (IL-10: 1.53-fold, IL-12: 1.22-fold, and IFN-γ: 1.20-fold), accompanied by substantial reductions in pro-inflammatory mediators (TGF-β1: 28.72% decrease and IL-21: 36.28% decrease). Concurrently, LP restored oxidative balance by increasing SOD, GSH, and NO levels in multiple organs (liver, kidneys, and small intestine) and serum. Mechanistic studies using an in vitro Caco-2/RAW264.7 coculture system revealed that four purified LP fractions (LPIa-LPIVa) effectively suppressed NF-κB pathway activation through downregulation of TLR4 expression, reduction of the p-IκB-α/IκB-α ratio, and inhibition of nuclear NF-κB translocation. These molecular effects correlated with decreased production of inflammatory mediators (TNF-α, IL-6, IL-8, iNOS, and NO). Collectively, these findings provide compelling evidence that LP possesses dual immunomodulatory and antioxidant capabilities, highlighting its potential as a natural adjuvant for alleviating chemotherapy-induced side effects.