Nerve Growth Factor-Inducing Activity of Hericium erinaceus in 1321 N 1 Human Astrocytoma Cells

Alzheimer’s disease, for which there is currently no effective therapy, is the most common senile dementia. Alzheimer’s disease patients have notable abnormalities in cholinergic neurons in the basal forebrain. Neurotrophic factors have potent biological activities, such as preventing neuronal death and promoting neurite outgrowth, and are essential to maintain and organize neurons functionally. Glial cells support neurons by releasing neurotrophic factors, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3, and glial-derived neurotrophic factor (GDNF). In particular, it is assumed that functional deficiency of NGF is related to Alzheimer’s disease and plays a part in the etiology of the disease process. It is known that NGF levels are decreased in the basal forebrains of Alzheimer’s disease patients, and in the frontal cortices of undemented patients with senile plaques. Furthermore, intracerebroventricular administration of NGF eliminates degeneration and resultant cognitive deficits in rats after brain injury, and it enhances the retention of passive avoidance learning in developing mice. In aged rats, intracerebral infusion of NGF partly reverses cholinergic cell body atrophy and improves the retention of spatial memory. In addition, intranasal administration of NGF ameliorates neurodegeneration and reduces the numbers of amyloid plaques in transgenic anti-NGF mice (AD11 mice), in which have a progressive neurodegenerative phenotype resembling Alzheimer’s disease. Therefore, NGF is expected to be applied to the treatment of Alzheimer’s disease. However, neurotrophic factors are proteins, and so are unable to cross the blood–brain barrier; they are also easily metabolized by peptidases. Therefore, their application as a medicine for the treatment of neurodegenerative disorders is assumed to be difficult. Alternatively, research has been carried out on low-molecular weight compounds that promote NGF biosynthesis, such as catecholamines, benzoquinones, fellutamides, idebenone, kansuinin, ingenol triacetate, jolkinolide B, dictyophorines, scabronines, hericenones, erinacins, and cyrneines. Hericium erinaceus is a mushroom that grows on old or dead broadleaf trees. H. erinaceus is taken as a food in Japan and China without harmful effects. Hericenones C—H and erinacines A—I were isolated from the fruit body and mycelium of H. erinaceus, respectively, all of which promote NGF synthesis in rodent cultured astrocytes. These results suggest the usefulness of H. erinaceus for the treatment and prevention of dementia. However, the detailed mechanism by which H. erinaceus induces NGF synthesis remains unknown. In the present study, we examined the NGF-inducing activity of ethanol extracts of H. erinaceus in 1321N1 human astrocytoma cells. The results obtained indicate that H. erinaceus has NGF-inducing activity, but that its active compounds are not hericenones. Furthermore, ICR mice given feed containing 5% H. erinaceus dry powder for 7 d showed an increase in the level of NGF mRNA expression in the hippocampus. September 2008 1727