Antidepressant-like effect of Ganoderma lucidum spore polysaccharide-peptide mediated by upregulation of prefrontal cortex brain-derived neurotrophic factor

Appl Microbiol Biotechnol. 2021 Dec;105(23):8675-8688. doi: 10.1007/s00253-021-11634-y. Epub 2021 Oct 30.


A 28-kDa polysaccharide-peptide (PGL) with antidepressant-like activities was isolated from spores of the mushroom Ganoderma lucidum. It was unadsorbed on DEAE-cellulose. Its internal amino acid sequences manifested pronounced similarity with proteins from the mushrooms Lentinula edodes and Agaricus bisporus. The monosaccharides present in 28-kDa PGL comprised predominantly of glucose (over 90%) and much fewer galactose, mannose residues, and other residues. PGL manifested antidepressant-like activities as follows. It enhanced viability and DNA content in corticosterone-injured PC12 cells(a cell line derived from a pheochromocytoma of the rat adrenal medulla with an embryonic origin from the neural crest containing a mixture of neuroblastic cells and eosinophilic cells) and reduced LDH release. A single acute PGL treatment shortened the duration of immobility of mice in both tail suspension and forced swimming tests. PGL treatment enhanced sucrose preference and shortened the duration of immobility in mice exposed to chronic unpredictable mild stress (CUMS). Chronic PGL treatment reversed the decline in mouse brain serotonin and norepinephrine levels but did not affect dopamine levels. PGL decreased serum corticosterone levels and increased BDNF mRNA and protein levels and increased synapsin I and PSD95 levels in the prefrontal cortex. This effect was completely blocked by pretreatment with the BDNF antagonist K252a, indicating that PGL increased synaptic proteins in a BDNF-dependent manner.Key points• An antidepressive polysaccharide-peptide PGL was isolated from G. lucidum spores.• PGL protected PC12 nerve cells from the toxicity of corticosterone.• PGL upregulated BDNF expression and influenced key factors in the prefrontal cortex.

Keywords: Antidepressant; Brain-derived neurotrophic factor; Corticosterone; Ganoderma lucidum spores; Monoamine neurotransmitters; Polysaccharide-peptide.

MeSH terms

  • Agaricus
  • Animals
  • Antidepressive Agents* / pharmacology
  • Brain-Derived Neurotrophic Factor* / genetics
  • Disease Models, Animal
  • Fungal Polysaccharides / pharmacology*
  • Mice
  • Peptides / pharmacology*
  • Prefrontal Cortex / metabolism
  • Rats
  • Reishi*
  • Spores, Fungal
  • Stress, Psychological
  • Sucrose
  • Up-Regulation


  • Antidepressive Agents
  • Brain-Derived Neurotrophic Factor
  • Fungal Polysaccharides
  • Peptides
  • Sucrose

Supplementary concepts

  • Agaricus bisporus