Hericium erinaceus mycelium and its isolated erinacine A protection from MPTP-induced neurotoxicity through the ER stress, triggering an apoptosis cascade

J Transl Med. 2016 Mar 18;14:78. doi: 10.1186/s12967-016-0831-y.

Abstract

Background: Hericium erinaceus is an edible mushroom; its various pharmacological effects which have been investigated. This study aimed to demonstrate whether efficacy of oral administration of H. erinaceus mycelium (HEM) and its isolated diterpenoid derivative, erinacine A, can act as an anti-neuroinflammatory agent to bring about neuroprotection using an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinson's disease, which results in motor disturbances, in addition to elucidating the mechanisms involved.

Methods: Mice were treated with and without HEM or erinacine A, after MPTP injection for brain injuries by the degeneration of dopaminergic nigrostriatal neurons. The efficacy of oral administration of HEM improved MPTP-induced loss of tyrosine hydroxylase positive neurons and brain impairment in the substantia nigra pars compacta as measured by brain histological examination.

Results: Treatment with HEM reduced MPTP-induced dopaminergic cell loss, apoptotic cell death induced by oxidative stress, as well as the level of glutathione, nitrotyrosine and 4-hydroxy-2-nonenal (4-HNE). Furthermore, HEM reversed MPTP-associated motor deficits, as revealed by the analysis of rotarod assessment. Our results demonstrated that erinacine A decreases the impairment of MPP-induced neuronal cell cytotoxicity and apoptosis, which were accompanied by ER stress-sustained activation of the IRE1α/TRAF2, JNK1/2 and p38 MAPK pathways, the expression of C/EBP homologous protein (CHOP), IKB-β and NF-κB, as well as Fas and Bax.

Conclusion: These physiological and brain histological changes provide HEM neuron-protective insights into the progression of Parkinson's disease, and this protective effect seems to exist both in vivo and in vitro.

Keywords: Endoplasmic reticulum stress; Erinacine A; Hericium erinaceus mycelium; Parkinson’s disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / administration & dosage
  • Agaricales / chemistry*
  • Animals
  • Apoptosis / drug effects*
  • Behavior, Animal
  • Brain / drug effects
  • Brain / pathology
  • Cell Line
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Diterpenes / chemistry
  • Diterpenes / isolation & purification*
  • Endoplasmic Reticulum Stress / drug effects*
  • Endoribonucleases / metabolism
  • MPTP Poisoning / drug therapy*
  • MPTP Poisoning / physiopathology
  • Mice, Inbred C57BL
  • Models, Biological
  • Motor Activity / drug effects
  • Mycelium / chemistry*
  • Neurons / drug effects
  • Neurons / pathology
  • Neuroprotection / drug effects*
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Neurotoxins / toxicity
  • Protein-Serine-Threonine Kinases / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects

Substances

  • Diterpenes
  • Neuroprotective Agents
  • Neurotoxins
  • Reactive Oxygen Species
  • erinacine A
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Ern1 protein, mouse
  • Protein-Serine-Threonine Kinases
  • Endoribonucleases