The Anti-Dementia effect of Lion's Mane mushroom and its clinical application - Hericium erinaceum - Lion's Mane

Townsend Letter for Doctors and Patients,  April, 2004  by Hirokazu Kawagishi,  Cun Zhuang,  Ellen Shnidman

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Introduction

Medicinal Mushrooms have become a hot item in the mass media in the last few years but the information being disseminated about them is not always scientifically accurate. Most of the studies on the efficacy of medicinal mushrooms that are available to the public are based on animal studies (usually in mice) or cultured cells. In these cases, the bioactivity of the mushroom extracts cannot always be correlated to their activity when ingested by humans--either orally or by injection.

Our research on components of Lion's Mane mushroom (Hericium erinaceum) and their biological activities in cell culture is a case where positive antidementia results in the laboratory have been confirmed by analogous results in human use. In this article, we will introduce both the results from the laboratory and their clinical application.

Conventional Treatments of Alzheimer's Disease

Alzheimer's disease is primarily a disorder of aging in which individuals become agitated and uncomprehending, with profound loss of cognitive function, ultimately requiring institutionalization. About 1 in 10 people over the age of 65 and as many as 5 out of 10 people over the age of 85 are affected. This disease is characterized biologically by the death of neurons in the forebrain, hippocampus, and cerebral cortex.

[FIGURE 1 OMITTED]

The most conventional approach to treatment of Alzheimer's disease currently in practice is to treat the symptoms caused by the death of cholinergic neurons. Four pharma-ceutical products approved by the FDA that are presently on the market work by potentiating neurotransmission at cholinergic synapses. These drugs are: Aricept[R] by Pfizer, Exelon[R] by Novartis, Reminyl[R] by Janssen, and Cognex[R] by First Horizon. None of these products, however, reverses the damage done to cognitive functioning. They simply delay further deterioration. Recently, a new drug called memantine, produced by Forest Laboratories, was approved for use by the FDA. Memantine works by blocking the receptor for the glutamate neurotransmitter whose overactivity may be responsible for the neurotoxicity of Alzheimer's disease. Likewise, its beneficial effect is only temporary.

Inducers of Nerve Growth Factor Synthesis in vitro

One of the major new approaches to the study of treatments for Alzheimer's disease concerns the search for agents that stimulate Nerve Growth Factor (NGF) production in the brain. NGF is part of a family of proteins that play a role in the maintenance, survival and regeneration of neurons during adult life. Its absence in the adult brain of mice leads to a condition resembling Alzheimer's disease.

Nerve Growth Factor itself cannot be used as an orally administered drug to regenerate brain tissue because it does not cross the blood-brain barrier. If bioactive substances with low molecular weight can be found that penetrate the barrier and induce the synthesis of NGF inside the brain, such substances may be applied as oral agents to prevent this disease. Even if these substances cannot go through the barrier, the enhancement of NGF production would be beneficial for disorders of the peripheral nervous system since NGF has a similar effect on neurons in the periphery.

We have been engaged in a study to search for NGF synthesis-promoting agents in medicinal mushrooms since 1991. We discovered a class of benzyl alcohol and chroman derivatives in the fruit body of Lion's Mane mushroom called the hericenones C-H that stimulate NGF production from mouse astroglial cells in culture. (1-18) Subsequently, we discovered another group of cyathane derivative compounds from the mycelium of the same mushroom called the erinacines A-I that also induce NGF production. (4-22) (Figure 1)

Hericenones Isolated from the Fruit Body of Lion's Mane

The hericenones were derived from Lion's Mane as follows. The fruit body of the mushroom was crushed in acetone by a blender and left for 1-2 days to allow extraction of nonpolar substances. The liquid extract was processed with vacuum filtration and the mushroom fruit body was further extracted twice by acetone. The extract was concentrated using an evaporator until 2 liters of volume was obtained, and then this was fractionated with chloroform. Ethyl acetate was added to the aqueous phase for an additional extraction.

The fractionation of the extract is an essential step for applying the compounds to the NGF assay, because there is an optimum concentration for the activation of NGF synthesis, and also most of the fractions at this stage exhibit cytotoxic activity. For separation purposes, silica gel chromatography and preparative thin layer chromatography (TLC) were employed, and two types of fractions were obtained: one with hericenones C-E and the other with hericenones F-H. Both fractions were spotted at almost the same distance on the silica gel TLC and thus separation was only possible by high performance liquid chromatography (HPLC), using an ODS column.

These compounds were the first active substances found in natural products that are as effective as epinephrine in inducing NGF synthesis in vitro. Each group of hericenones, C-E and F-H, contains a characteristic alcohol site, and each hericenone contains one of three simple fatty acids. Hericenone D demonstrated the strongest stimulating activity in synthesis of NGF from astroglial cells. The activity level of these compounds varies according to the structure of its fatty acid constituent.