title: Hericium erinaceus mycelium and its isolated erinacine A protection from MPTP-induced neurotoxicity through the ER stress, triggering an apoptosis cascade.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Nursing, Chang Gung University of Science and Technology, Chiayi, Taiwan.|Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.
authors.forename: Hsing-Chun
authors.initials: HC
authors.lastname: Kuo
authors.affiliation: Division of Colorectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Chien-Chang
authors.initials: CC
authors.lastname: Lu
authors.affiliation: Department of Hepato-Gastroenterology, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: Chien-Heng
authors.initials: CH
authors.lastname: Shen
authors.affiliation: Department of Hepato-Gastroenterology, Chang Gung Memorial Hospital, Chiayi, Taiwan.|Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Shui-Yi
authors.initials: SY
authors.lastname: Tung
authors.affiliation: Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: Meng Chiao
authors.initials: MC
authors.lastname: Hsieh
authors.affiliation: Division of Colorectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Ko-Chao
authors.initials: KC
authors.lastname: Lee
authors.affiliation: Grape King Biotechnology Inc., Zhong-Li, Taiwan.
authors.forename: Li-Ya
authors.initials: LY
authors.lastname: Lee
authors.affiliation: Grape King Biotechnology Inc., Zhong-Li, Taiwan.
authors.forename: Chin-Chu
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Nursing, Chang Gung University of Science and Technology, Chiayi, Taiwan.
authors.forename: Chih-Chuan
authors.initials: CC
authors.lastname: Teng
authors.affiliation: Chang Gung University College of Medicine, Taoyuan, Taiwan.|Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: Wen-Shih
authors.initials: WS
authors.lastname: Huang
authors.affiliation: Division of Nephrology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Te-Chuan
authors.initials: TC
authors.lastname: Chen
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital, Chiayi, Taiwan. lkf2758@gmail.com.
authors.forename: Kam-Fai
authors.initials: KF
authors.lastname: Lee
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage; D000363:Agaricales / Q000737:chemistry*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001522:Behavior, Animal; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004722:Endoribonucleases / Q000378:metabolism; D020267:MPTP Poisoning / Q000188:drug therapy* / Q000503:physiopathology; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009043:Motor Activity / Q000187:drug effects; D025282:Mycelium / Q000737:chemistry*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D000066829:Neuroprotection / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D009498:Neurotoxins / Q000633:toxicity; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004224:Diterpenes; D018696:Neuroprotective Agents; D009498:Neurotoxins; D017382:Reactive Oxygen Species; C000595639:erinacine A; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C510185:Ern1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases
keywords: Endoplasmic reticulum stress; Erinacine A; Hericium erinaceus mycelium; Parkinson’s disease