title: Hericium erinaceus (Bull.: Fr) Pers. cultivated under tropical conditions: isolation of hericenones and demonstration of NGF-mediated neurite outgrowth in PC12 cells via MEK/ERK and PI3K-Akt signaling pathways.
abstract: Hericium erinaceus (Bull.: Fr.) Pers. is an edible and medicinal mushroom used traditionally to improve memory. In this study, we investigated the neuritogenic effects of hericenones isolated from H. erinaceus and the mechanisms of action involved. H. erinaceus was cultivated and the secondary metabolites were elucidated by high performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR). The secondary metabolites were tested for neurite outgrowth activity (if any). Rat pheochromocytoma (PC12) cells were employed and the nerve growth factor (NGF) level was also determined. The signaling pathways involved in the mushroom-induced neuritogenesis were investigated using several pharmacological inhibitors. Hericenones B-E (1-4), erinacerin A (5) and isohericerin (6) were isolated from the basidiocarps of H. erinaceus. The hericenones did not promote neurite outgrowth but when induced with a low concentration of NGF (5 ng mL(-1)), the neuritogenic activity was comparable to that of the positive control (50 ng mL(-1) of NGF). Hericenone E was able to stimulate NGF secretion which was two-fold higher than that of the positive control. The neuritogenesis process was partially blocked by the tyrosine kinase receptor (Trk) inhibitor, K252a, suggesting that the neuritogenic effect was not solely due to NGF. Hericenone E also increased the phosphorylation of extracellular-signal regulated kinases (ERKs) and protein kinase B (Akt). Taken together, this study suggests that hericenone E potentiated NGF-induced neuritogenesis in PC12 cells via the MEK/ERK and PI3K/Akt pathways.
authors.affiliation: Mushroom Research Centre, University of Malaya, 50603 Kuala Lumpur, Malaysia. viki@um.edu.my.
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Phan
authors.forename: Guan-Serm
authors.initials: GS
authors.lastname: Lee
authors.forename: Sok-Lai
authors.initials: SL
authors.lastname: Hong
authors.forename: Yuin-Teng
authors.initials: YT
authors.lastname: Wong
authors.forename: Robert
authors.initials: R
authors.lastname: Brkljača
authors.forename: Sylvia
authors.initials: S
authors.lastname: Urban
authors.forename: Sri Nurestri
authors.initials: SN
authors.lastname: Abd Malek
authors.forename: Vikineswary
authors.initials: V
authors.lastname: Sabaratnam
mesh_terms: D000818:Animals; D001487:Basidiomycota / Q000737:chemistry* / Q000254:growth & development; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020932:Nerve Growth Factor / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D016716:PC12 Cells; D010636:Phenols / Q000302:isolation & purification / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D014675:Vegetables / Q000737:chemistry* / Q000254:growth & development
chemical_list: D010636:Phenols; D010936:Plant Extracts; C532218:hericenone E; D020932:Nerve Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt