The Cyanthin Diterpenoid and Sesterterpene Constituents of Hericium erinaceus Mycelium Ameliorate Alzheimer's Disease-Related Pathologies in APP/PS1 Transgenic Mice

Int J Mol Sci. 2018 Feb 17;19(2):598. doi: 10.3390/ijms19020598.


Hericium erinaceus was used in traditional Chinese medicine for physiologically beneficial medicines. Recently, it has become a candidate in causing positive brain health-related activities. We previously reported that Hericium erinaceus mycelium ameliorates Alzheimer's disease (AD)-related pathologies. To reveal the role of the cyanthin diterpenoid and sesterterpene constituents on this effects, erinacine A and S were isolated and their effects on attenuating AD-related pathology in APPswe/PS1dE9 transgenic mice were investigated. A 30 day short-term administration of erinacine A and S were performed to explore the effect of each erinacine on AD-related pathology including amyloid β production and degradation, plaque formation, plaque growth, glial activation and neurogenesis deterioration. Our results indicated the benefit effects of both erinacine A and S in cerebrum of APPswe/PS1dE9 mice, including: (1) attenuating cerebral plaque loading by inhibiting plaque growth; (2) diminishing the activation of glial cells; (3) raising the level of insulin degrading enzyme; and (4) promoting hippocampal neurogenesis. Moreover, erinacine A reduced the level of insoluble amyloid β and C-terminal fragment of amyloid precursor protein which was not mediated by erinacine S. We further performed a long term administration of erinacine A and found that erinacine A recovered the impairment in the tasks including burrowing, nesting, and Morris water maze. Our data pointed out that although both erinacine A and S reduce AD pathology via reducing amyloid deposition and promoting neurogenesis, erinacine A can also inhibit amyloid β production and is worth to be further developed for AD therapeutic use.

Keywords: APPswe/PS1dE9 transgenic mice; Alzheimer’s disease; amyloid plaque; astrocytes; erinacines; microglia; neurogenesis.

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology
  • Amyloid Precursor Protein Secretases / genetics
  • Amyloid beta-Peptides / antagonists & inhibitors
  • Amyloid beta-Peptides / genetics
  • Animals
  • Basidiomycota / chemistry
  • Diterpenes / administration & dosage
  • Diterpenes / chemistry
  • Hippocampus / drug effects
  • Hippocampus / growth & development
  • Humans
  • Insulysin / genetics
  • Mice
  • Mice, Transgenic
  • Mycelium / chemistry
  • Neurogenesis / drug effects*
  • Neuroglia / drug effects
  • Oligopeptides / genetics
  • Plaque, Amyloid / drug therapy*
  • Plaque, Amyloid / genetics
  • Plaque, Amyloid / pathology
  • Protein Aggregation, Pathological / drug therapy*
  • Protein Aggregation, Pathological / genetics
  • Protein Aggregation, Pathological / pathology
  • Sesterterpenes / administration & dosage
  • Sesterterpenes / chemistry


  • Amyloid beta-Peptides
  • Diterpenes
  • Oligopeptides
  • PS1 antigen
  • Sesterterpenes
  • erinacine A
  • erinacine S
  • Amyloid Precursor Protein Secretases
  • Insulysin