Abstract

BackgroundHericium 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.MethodsMice 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.ResultsTreatment 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.ConclusionThese 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.

Highlights

  • Hericium erinaceus is an edible mushroom; its various pharmacological effects which have been investi‐ gated

  • The cells were seeded at 2 × 104 cells/ml density and Hericium erinaceus mycelium (HEM) inhibits the cytotoxic effect of neuron cells in the MPTP‐treatment animal model Our previous study demonstrated that H. erinaceus mycelium and its structural analog erinacine A have nerve-growth properties, allowing them to aid in the prevention of ischemic injury to neurons in the central nervous system of excessive oxidative stress subjects [12, 13]

  • Representative brain sections stained as saline infusion control group (I); Mice with MPTP injection (II); HEM treatment (10.76 and 21.52 mg/day) (III, IV); Apoptotic cells were measured under microscopy as described in “Methods” section

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Summary

Introduction

Hericium erinaceus is an edible mushroom; its various pharmacological effects which have been investi‐ gated. 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 neuroprotec‐ tion 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. Hericium erinaceus (Lion’s mane or Yamabushitake) is an edible mushroom with medicinal properties; it grows on old or dead broadleaf trees. It is used as a food and herbal medicine in Japan and China without harmful effects [1]. The mechanism by which H. erinaceus mycelium and its isolated diterpenoid derivative, erinacine A, promote neuron cell survival and protection from MPTP-induced neurotoxicity remains poorly understood, as does the mechanism by which H. erinaceus mycelium and erinacine A initiate neuroprotection against MPTP injury to the brain

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