Lignosus rhinocerotis (Cooke) Ryvarden Induces Neuritogenesis via Extracellular Signal-Regulated Kinase (ERK) Pathway in Rat Pheochromocytoma Cells

摘要

Neuritogenic activity has become one of the focuses of study in search of preventive and therapeutic agents for neurodegenerative diseases.As one factor in the neurotrophin family,nerve growth factor (NGF) has potent biological activities,e.g.Promoting neuronal survival,proliferation,neuritogenesisand it is expected to be applied to the treatment of neurodegenerative diseases.Among the natural sources explored for NGF mimics,the potential of culinary and medicinal mushrooms has attracted intense interest.Traditional application of the sclerotium of Lignosus rhinocerotis by the indigenous folks as remedy and tonic to treat variety of ailments has beendocumented in Malaysia.This study aimed to investigate the potential of NGF-like activity ofL.rhinocerotis which may contribute to the prevention and treatment of the neurodegenerative diseases.The neuroendocrine cell line,rat pheochromocytoma (PC-12),was used as an in vitro model in this study.Nerve growth factor (50 ng/ml) was used as a positive control.The aqueous extract ofL.rhinocerotis sclerotium promoted neuritogenesisin PC-12 cells significantly (p＜0.05) at a low concentration (25 tg/ml).The involvement of the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK1/2) signaling pathway in aqueous extract-induced neuritogenesis was investigated using two specific inhibitors of the MEK/ERK1/2 pathway (U0126 and PD98059).The neuritogenic activity of aqueous extract was blocked by these inhibitors significantly (p＜0.001).Furthermore,the protein expression of total p44/42 MAPK (Erk1/2) and phosphor-p44/42 MAPK was determined.The data revealed the first evidence of the involvement of MEK/ERK1/2 signalling pathway in aqueous extract of L.rhinocerotis sclerotium-inducedneuritogenesis in PC-12 cells.