Sarcodon imbricatus polysaccharides protect against cyclophosphamide-induced immunosuppression via regulating Nrf2-mediated oxidative stress

Sarcodon imbricatus, a rare medicinal and edible fungus, has various pharmacological bioactivities. The present study systematically investigated the protective effects of S. imbricatus polysaccharides (SIPS) against cyclophosphamide (CTX)-induced immunosuppression in Balb/c mice model. Compared with the CTX-induced immunosuppressive mice, the spleen and thymus indexes in the mice with 28-day SIPS orally administration were significantly increased, bodyweight loss was alleviated, and the natural killer (NK) cytotoxicity and the proliferative activities of lymphocytes were elevated. SIPS regulated the production of immunoglobulins including IgA, IgG and IgM in the serum and spleen. Notably, SIPS promoted the secretion of interleukin-2 (IL-2), IL-6, IL-10, IL-12 and interferon-γ (IFN-γ) of serum and spleen in CTX-induced immunosuppressive mice. Additionally, SIPS inhibited reactive oxygen species (ROS) levels and increased total antioxidant capacity, including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities of spleen and thymus, as well as enhanced acid phosphatase (ACP) and lysozyme (LZM) levels of thymus in CTX-induced immunosuppressive mice. Histopathological analysis of spleen revealed the protective effect of SIPS against CTX-induced immunosuppression. More importantly, SIPS promoted the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2) and its downstream target genes encoding antioxidant enzymes: SOD1, SOD2, haem oxygenase-1 (HO-1), CAT and quinone oxidoreductase 1 (NQO1). Altogether, SIPS reversed CTX-induced immunosuppression effectively and predominantly through Nrf2-mediated oxidative stress, which provided the useful evidence that SIPS can be served as a novel natural immunomodulator in health foods or medicine.