title: Protective effects of Hericium erinaceus mycelium and its isolated erinacine A against ischemia-injury-induced neuronal cell death via the inhibition of iNOS/p38 MAPK and nitrotyrosine.
abstract: Hericium erinaceus, an edible mushroom, has been demonstrated to potentiate the effects of numerous biological activities. The aim of this study was to investigate whether H. erinaceus mycelium could act as an anti-inflammatory agent to bring about neuroprotection using a model of global ischemic stroke and the mechanisms involved. Rats were treated with H. erinaceus mycelium and its isolated diterpenoid derivative, erinacine A, after ischemia reperfusion brain injuries caused by the occlusion of the two common carotid arteries. The production of inflammatory cytokines in serum and the infracted volume of the brain were measured. The proteins from the stroke animal model (SAM) were evaluated to determine the effect of H. erinaceus mycelium. H. erinaceus mycelium reduced the total infarcted volumes by 22% and 44% at a concentration of 50 and 300 mg/kg, respectively, compared to the SAM group. The levels of acute inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor á, were all reduced by erinacine A. Levels of nitrotyrosine-containing proteins, phosphorylation of p38 MAPK and CCAAT enhancer-binding protein (C/EBP) and homologous protein (CHOP) expression were attenuated by erinacine A. Moreover, the modulation of ischemia injury factors present in the SAM model by erinacine A seemed to result in the suppression of reactive nitrogen species and the downregulation of inducible NO synthase (iNOS), p38 MAPK and CHOP. These findings confirm the nerve-growth properties of Hericium erinaceus mycelium, which include the prevention of ischemic injury to neurons; this protective effect seems to be involved in the in vivo activity of iNOS, p38 MAPK and CHOP.
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan. lkf2002@adm.cgmh.org.tw.
authors.forename: Kam-Fai
authors.initials: KF
authors.lastname: Lee
authors.affiliation: Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan. chenjiannhwa@yahoo.com.tw.
authors.forename: Jiann-Hwa
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Department of Nursing and Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chiayi 61363, Taiwan. ccteng5648@gmail.com.
authors.forename: Chih-Chuan
authors.initials: CC
authors.lastname: Teng
authors.affiliation: Department of Hepato-Gastroenterology, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan. gi2216@adm.cgmh.org.tw.
authors.forename: Chien-Heng
authors.initials: CH
authors.lastname: Shen
authors.affiliation: Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan. mr8872@gmail.com.
authors.forename: Meng-Chiao
authors.initials: MC
authors.lastname: Hsieh
authors.affiliation: Department of Colorectal Surgery and Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan. cclu999@gmail.com.
authors.forename: Chien-Chang
authors.initials: CC
authors.lastname: Lu
authors.affiliation: Department of Colorectal Surgery and Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan. kmch4329@gmail.com.
authors.forename: Ko-Chao
authors.initials: KC
authors.lastname: Lee
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan. ly.lee@grapeking.com.tw.
authors.forename: Li-Ya
authors.initials: LY
authors.lastname: Lee
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan. wp.chen@grapeking.com.tw.
authors.forename: Wan-Ping
authors.initials: WP
authors.lastname: Chen
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan. gkbioeng@grapeking.com.tw.
authors.forename: Chin-Chu
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan. wen1204@adm.cgmh.org.tw.
authors.forename: Wen-Shih
authors.initials: WS
authors.lastname: Huang
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan. guscsi@gmail.com.
authors.forename: Hsing-Chun
authors.initials: HC
authors.lastname: Kuo
mesh_terms: D000818:Animals; D001487:Basidiomycota / Q000737:chemistry*; D002545:Brain Ischemia / Q000188:drug therapy*; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016923:Cell Death; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D025282:Mycelium / Q000737:chemistry; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D016207:Cytokines; D004224:Diterpenes; D018696:Neuroprotective Agents; C000595639:erinacine A; D051742:Transcription Factor CHOP; C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II; D048051:p38 Mitogen-Activated Protein Kinases