Se-enriched G. frondosa polysaccharide protects against immunosuppression in cyclophosphamide-induced mice via MAPKs signal transduction pathway

Carbohydr Polym. 2018 Sep 15:196:445-456. doi: 10.1016/j.carbpol.2018.05.046. Epub 2018 May 17.

Abstract

To assess the immunomodulatory and antioxidant activities of a Se-polysaccharide from Se-enriched G. frondosa (Se-GFP-22), immunosuppressed mice models were generated by cyclophosphamide (CTX) administration and then treated with Se-GFP-22. Results showed that Se-GFP-22 could increase thymus and spleen indices, phagocytic index, co-mitogenic (ConA- or LPS-stimulated) activities on splenocytes, DTH reaction, serum hemolysin formation and immunoglobulin (Ig G, Ig A and Ig M) levels in CTX-treated mice. Se-GFP-22 significantly enhanced the antioxidant activity in CTX-treated mice, as shown by the evaluation of GSH-Px, SOD and CAT activities, as well as MDA levels in serum, liver and kidney. Se-GFP-22 strongly stimulated inflammatory cytokines (IL-2 and IFN-γ) and NO productions by up-regulating mRNA expressions of IL-2, IFN-γ and iNOS. Se-GFP-22 possessed the immunomodulatory activity by up-regulating various transcription factors (JNK, ERK, and p38) in MAPKs signaling pathways. This study suggested that Se-GFP-22 may provide an alternative strategy in lessening chemotherapy-induced immunosuppression.

Keywords: Antioxidant activity; Cyclophosphamide; Immunomodulatory activity; MAPKs; Se-enriched Grifola frondosa; Selenium polysaccharide.

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Cyclophosphamide / pharmacology*
  • Fungal Polysaccharides / chemistry*
  • Fungal Polysaccharides / pharmacology*
  • Gene Expression Regulation, Enzymologic / drug effects
  • Grifola / chemistry*
  • Immunosuppressive Agents / pharmacology*
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Interleukin-2 / genetics
  • Interleukin-2 / metabolism
  • Lymphocytes / cytology
  • Lymphocytes / drug effects
  • MAP Kinase Signaling System / drug effects*
  • Mice
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Selenium / chemistry*
  • Spleen / drug effects
  • Spleen / immunology
  • Thymus Gland / drug effects
  • Thymus Gland / immunology

Substances

  • Fungal Polysaccharides
  • Immunosuppressive Agents
  • Interleukin-2
  • RNA, Messenger
  • Nitric Oxide
  • Interferon-gamma
  • Cyclophosphamide
  • Nitric Oxide Synthase Type II
  • Selenium