A new GlcNAc-containing polysaccharide from Morchella importuna fruiting bodies: Structural characterization and immunomodulatory activities in vitro and in vivo

Int J Biol Macromol. 2021 Dec 1:192:1134-1149. doi: 10.1016/j.ijbiomac.2021.10.051. Epub 2021 Oct 15.

Abstract

This study investigated the purification and characterization of a new immunomodulatory GlcNAc-containing polysaccharide (MIPB70-1) from Morchella importuna with molecular weights of 20.6 kDa. Structural analysis indicated that MIPB70-1 was composed of GlcNAc:Gal:Glc:Man with molar ratios of 1.00:7.16:5.54:5.61, and its primary structure was characterized as a repeating unit consisting of →6)-α-D-Glcp-(1→, α-D-GlcpNAc-(1→, α-D-Galp-(1→, β-D-Glcp-(1→, →6)-α-D-Manp-(1→, →4)-α-D-GlcpNAc-(1→, →4)-β-D-Glcp-(1→, →3,6)-α-D-Manp-(1→, →2)-α-D-Galp-(1→, →2,3,6)-α-D-Manp-(1→. Immunological assays indicated that MIPB70-1 enhanced the phagocytic function and promoted the secretion of nitric oxide (NO) as well as cytokines through targeting Toll-like receptor 4 (TLR4) on macrophage membrane and activating the downstream signaling pathways in RAW 264.7 cells. MIPB70-1 regulated mouse immunity to counteract the immune damage caused by the chemotherapy drug cyclophosphamide (CTX) in vivo. Furthermore, MIPB70-1 enhanced the anti-tumor activity of doxorubicin (DOX) and inhibited the growth of tumors, by immunomodulation in the orthotopic murine model of 4T1 breast cancer. These results demonstrate the potential of this GlcNAc-containing polysaccharide as an immune enhancer.

Keywords: Immunomodulatory activities in vitro and in vivo; Morchella importuna GlcNAc-containing polysaccharide; Structural characterization.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Ascomycota / chemistry*
  • Cytokines / biosynthesis
  • Fruiting Bodies, Fungal / chemistry*
  • Fungal Polysaccharides / chemistry*
  • Gas Chromatography-Mass Spectrometry
  • Immunologic Factors / chemistry*
  • Immunologic Factors / pharmacology*
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages / metabolism
  • Magnetic Resonance Spectroscopy
  • Mice
  • Models, Biological
  • Molecular Weight
  • Monosaccharides
  • Nitric Oxide / biosynthesis
  • RAW 264.7 Cells
  • Signal Transduction / drug effects
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Cytokines
  • Fungal Polysaccharides
  • Immunologic Factors
  • Monosaccharides
  • Nitric Oxide

Supplementary concepts

  • Morchella importuna