Sulfated polysaccharide from Antrodia cinnamomea mycelium cultured with zinc sulfate stimulates M1 polarization of macrophages through AKT/mTOR pathways

Int J Biol Macromol. 2024 Nov;279(Pt 4):135548. doi: 10.1016/j.ijbiomac.2024.135548. Epub 2024 Sep 11.

Abstract

Antrodia cinnamomea-derived sulfated polysaccharides (Ac-SPSs) have health benefits, but their yield is low. This study explores a strategy to increase Ac-SPS yield and elucidates the biofunctions of Ac-SPS. For this, A. cinnamomea mycelia were treated with zinc sulfate (ZnSO4) administered at 1, 10, and 100 μM. Firstly, functional assay indicated that ZnSO4 increases the Ac-SPS yield by 20 %-30 % compared with the control treatment. ZnSO4 engenders a population of middle-molecular-weight (~200 kDa) Ac-SPSs. Ac-SPS (ASZ-10) from A. cinnamomea treated with 10 μM ZnSO4 exhibits the best anti-proliferation ability against lung cancer A549 cells. Co-treatment of ASZ-10 does not inhibit lipopolysaccharide-induced inflammation but does induce M1-related markers of macrophage RAW264.7 cells. Secondly, immunomodulatory properties showed that ASZ-10 increases the expression of CD80+ and CD86+ in M-CSF-stimulated bone-marrow-derived macrophages. ASZ-10 induces M1 polarization through up-regulation of the AKT/mTOR pathway as confirmed by AKT and mTOR inhibitors eliminating ASZ-10-induced M1-like markers of macrophages. Through systemic chemical and functional analysis, this study shows that trace amounts (10 μM) of ZnSO4 increase Ac-SPS yield and it reveals that ASZ-10 exhibits anti-cancer activity and acts as a stimulator for M1 macrophages by stimulation of AKT and mTOR.

Keywords: Antrodia cinnamomea; Biochemical characterization; Macrophage; Sulfated polysaccharides; Zinc sulfate.

MeSH terms

  • A549 Cells
  • Animals
  • Antrodia / chemistry
  • Cell Proliferation / drug effects
  • Fungal Polysaccharides / chemistry
  • Fungal Polysaccharides / pharmacology
  • Humans
  • Macrophages* / drug effects
  • Macrophages* / metabolism
  • Mice
  • Mycelium* / chemistry
  • Polyporales / chemistry
  • Polysaccharides* / chemistry
  • Polysaccharides* / pharmacology
  • Proto-Oncogene Proteins c-akt* / metabolism
  • RAW 264.7 Cells
  • Signal Transduction* / drug effects
  • Sulfates / chemistry
  • Sulfates / pharmacology
  • TOR Serine-Threonine Kinases* / metabolism
  • Zinc Sulfate* / chemistry
  • Zinc Sulfate* / pharmacology

Substances

  • TOR Serine-Threonine Kinases
  • Zinc Sulfate
  • Proto-Oncogene Proteins c-akt
  • Polysaccharides
  • Sulfates
  • Fungal Polysaccharides