Nerve Growth Factor-Inducing Activity of Hericium erinaceus in 1321N1 Human Astrocytoma Cells
Neurotrophic factors are essential to maintain and organize neurons functionally; thereby neurotrophic factor-like substances or their inducers are expected to be applied to the treatment of neurodegenerative diseases such as Alzheimer’s disease. In the present study, we firstly examined the effects of ethanol extracts of four edible mushrooms, Hericium erinaceus (Yamabushitake), Pleurotus eryngii (Eringi), Grifola frondosa (Maitake), andAgaricus blazei (Himematsutake), on nerve growth factor (NGF) gene expression in 1321N1 human astrocytoma cells. Among the four mushroom extracts, only H. erinaceus extract promoted NGF mRNA expression in a concentration-dependent manner. In addition, secretion of NGF protein from 1321N1 cells was enhanced by H. erinaceus extracts, and the conditioned medium of 1321N1 cells incubated with H. erinaceus extract enhanced the neurite outgrowth of PC12 cells. However, hericenones C, D and E, constituents of H. erinaceus, failed to promote NGF gene expression in 1321N1 cells. The enhancement of NGF gene expression by H. erinaceus extracts was inhibited by the c-jun N-terminal kinase (JNK) inhibitor SP600125. In addition, H. erinaceus extracts induced phosphorylation of JNK and its downstream substrate c-Jun, and increased c-fos expression, suggesting that H. erinaceus promotes NGF gene expression via JNK signaling. Furthermore we examined the efficacy of H. erinaceus in viva. ddY 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. In conclusion, H. erinaceus contains active compounds that stimulate NGF synthesis via activation of the JNK pathway; these compounds are not hericenones.
Compounds for dementia from Hericium erinaceum
The group conducted a search for compounds for dementia derived from medicinal mushrooms since 1991. A series of benzyl alcohol derivatives (named hericenones C to H), as well as a series of diterpenoid derivatives (named erinacines A to I) were isolated from the mushroom Hericium erinaceum. These compounds significantly induced the synthesis of nerve growth factor (NGF) in vitro and in vivo. In a recent study, dilinoleoyl-phosphatidylethanolamine (DLPE) was isolated from the mushroom and was found to protect against neuronal cell death caused by b-amyloid peptide (Ab) toxicity, endoplasmic reticulum (ER) stress and oxidative stress. Furthermore, the results of preliminary clinical trials showed that the mushroom was effective in patients with dementia in improving the Functional Independence Measure (FIM) score or retarding disease progression.
Neurotropic and Trophic Action of Lion’s Mane Mushroom Hericium erinaceus (Bull.: Fr.) Pers. (Aphyllophoromycetideae) Extracts on Nerve Cells in Vitro
The neurotropic and trophic effect of extract obtained from the edible and medicinal mushroomHericium erinaceus on nerve cells was studied. Spike reactions of hippocampal neurons during application of H. erinaceus fruiting bodies extract were studied on rat brain slices in vitro, using whole-cell patch clamp recording. Spike activity was inhibited in a concentration-dependent, reversible manner in 34%−90% of studied neurons by extracts obtained with ethanol, ether, or broth. Extract suppressed the excitation of neurons caused by L-glutamic acid application. The assumption is made that the H. erinaceus extract contains substances that may activate receptors that cause an inhibition of spike activity. The inhibitory effect of extract was not induced by GABA and serotonin receptor activation or activation of M- and N-cholinoreceptors. Inhibition of spike activity was caused by hyperpolarization of the neuronal membrane during extract application. The hyperpolarization was accompanied by an increase of apamin-sensitive Ca-activated K+ current (IAHP) and apamin-insensitive, slow Ca-activated K+ current (sIAHP), but it was not caused by an increase of inward rectifier K+ current (I(ir)) or by changes of hyperpolarization-activated cationic currents (I(h)). The effect of the extract was observed in the presence of tetrodotoxin, suggesting that the extract acts postsynaptically. Extract application did not suppress biochemical processes in cell respiratory circuits. The extract did not affect the regenerating abilities of the neurons and glial cells of the cerebellum and hippocampus. It was demonstrated that the H. erinaceus extract concentrate exerted neurotropic action and improved the myelination process in the mature myelinating fibers, did not affect nerve cell growth in vitro, and did not evoke a toxic effect or nerve cell damage.