Investigating the therapeutic potential of Hericium erinaceus mycelium on Alzheimer's disease

• Main Authors: Tsai-Teng Tzeng, 曾才騰
• Other Authors: Young-Ji Shiao
• Format: Others
• Language: en_US
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/07469553199458842298

博士 === 國立陽明大學 === 生物藥學研究所 === 104 === Alzheimer’s disease (AD) is the most common neurodegenerative disease, possibly caused by abnormal accumulation of β-amyloid peptide (Aβ) and insufficiency of neurotrophic factors. Erinacine A, an active compound from mycelium of Hericium erinaceus, is known to have a potent stimulating effect on nerve growth factor (NGF) synthesis which may be used to counteract the degeneration of cholinergic systems known to occur in AD patients. Recent studies demonstrated anti-dementia activity of fruiting body of H. erinaceus in mouse model and in subject with mild cognitive impairment. However, the effect of erinacine A on AD pathogenesis remains unclear. In this study, two erinacine A-enriched unpurified components, including H. erinaceus mycelium and its ethanol crude extract, and two major compounds, including erinacine A and erinacine S (a novel sesterterpene in H. erinaceus mycelium), were used to investigate the therapeutic effect in 5 months old APPswe/PS1dE9 transgenic mice. The results showed that erinacine A and erinacine S significantly attenuated the plaque loading by affecting both their filamentary and compact core structure, and that erinacine A obviously reduced insoluble amyloid-β level. On the other hand, two erinacine A-enriched components reduced plaque loading by affecting their filamentary structure only. Additionally, the treatment of these four components also ameliorated AD pathology by (1) diminishing the plaque-associated glial cells, (2) reducing the level of matrix metalloproteinase-9, (3) increasing the level of NGF and insulin-degrading enzyme in cortex, and (4) promoting neurogenesis in dentate gyrus. However, only erinacine A significantly attenuates the production of APP C-terminal fragments-α and -β. Long-term treatment of erinacine A and H. erinaceus mycelium reduced serum amyloid-β level, which may be mediated by raising the level of insulin-degrading enzyme in liver. Notably, the results from long- and short-term treatment showed that erinacine A attenuated the formation of new plaque. Prolonged administration of erinacine A and H. erinaceus mycelium successfully recovered the deficits on activity of daily living, including on burrowing and nesting tasks, in APPswe/PS1dE9 transgenic mice. Furthermore, administration of erinacine A also significantly ameliorated the deficits on the spatial learning and memory ability on Morris water maze task in APPswe/PS1dE9 transgenic mice. Our data pointed out that the components from H. erinaceus mycelium reduce AD-related pathology, especially erinacine A, which highlights its therapeutic potential on AD.