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Neurological Activity of Lion’s Mane ( Hericium erinaceus )


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Hericium erinaceus, most commonly known as lion’s mane, is an edible fungus, with a long history of use in Traditional Chinese Medicine. The mushroom is abundant in bioactive compounds including β-glucan polysaccharides; hericenones and erinacine terpenoids; isoindolinones; sterols; and myconutrients, which potentially have neuroprotective and neuroregenerative properties. Because of its anti-inflammatory properties and promotion of nerve growth factor gene expression and neurite (axon or dendrite) outgrowth, H. erinaceus mycelium shows great promise for the treatment of Alzheimer’s and Parkinson’s diseases. The fungus was well tolerated in two clinical studies, with few adverse events reported.
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Journal of Restorative Medicine 2017; 6: page 19
Neurological Activity of Lion’s Mane (Hericium erinaceus)
Kevin Spelman, PhD, MCPPa
Elizabeth Sutherland, NDb
Aravind Bagade, MDc
©2017, Kevin Spelman, PhD, MCPP
Journal Compilation ©2017, AARM
DOI 10.14200/jrm.2017.6.0108
Hericium erinaceus, most commonly known as lion’s mane, is an edible fungus, with
a long history of use in Traditional Chinese Medicine. The mushroom is abundant in
bioactive compounds including β-glucan polysaccharides; hericenones and erinacine
terpenoids; isoindolinones; sterols; and myconutrients, which potentially have
neuroprotective and neuroregenerative properties. Because of its anti-inflammatory
properties and promotion of nerve growth factor gene expression and neurite
(axon or dendrite) outgrowth, H. erinaceus mycelium shows great promise for the
treatment of Alzheimer’s and Parkinson’s diseases. The fungus was well tolerated in
two clinical studies, with few adverse events reported.
Keywords: Lion’s mane; Neuroregeneration; Neurodegeneration; Neuroprotection;
Neurotropins; Neurotrophic; Alzheimer’s disease; Parkinson’s disease; Multiple
Sclerosis; Nerve growth factor
aCorresponding author: Health, Education & Research, POB 599, Ashland, OR 97520, USA,
Tel.: +1-541-708-3002; E-mail:
bAdjunct faculty National University of Natural Medicine, Portland, OR, USA
cExecutive Secretary and Researcher, Ayurveda Interdisciplinary Research Minds Association, Mysore, India
Journal of Restorative Medicine 2017; 6: page 20
Lion’s Mane Neurological Activity
Ancient, traditional, and modern cultures around
the world have known about the nutritive and
medicinal properties of mushrooms for centu-
ries. As early as 450 BCE, the Greek physician
Hippocrates identified mushrooms as potent
anti-inflammatory agents, useful for cauterizing
wounds. In the East, reverence for fungi is evident
in the Chinese description of ling zhi (Ganoderma
lucidum), as the “spirit plant,” believed to provide
longevity and spiritual potency.
Modern medicine has been slower to catch on to
the immense potential of fungi. Despite Fleming’s
1929 discovery of penicillin,1 and the subsequent
implementation of the fungi-chemical as a block-
buster pharmaceutical in the 1940s,2 it is only
in the last few decades that medical science has
looked beyond the antimicrobial and cholesterol-
lowering properties of fungi for other potential
Clinicians now have greater access to myce-
lium extracts, which are used clinically for their
cytotoxic, antineoplastic, cardiovascular, anti-
inflammatory, and immune-modulating activities.3–5
Functional studies and chemical assays also support
their potential to act as analgesic, antibacterial,
antioxidant, and neuroprotective agents. A number
of mushrooms, including Sarcodon scabrosus,
Ganoderma lucidum, Grifola frondosa, and
Hericium erinaceus are reported to have activi-
ties related to nerve and brain health.6 Hericium
erinaceus, a member of the Herinaceae family, is a
culinary and medicinal mushroom. Both the myce-
lium and fruiting bodies of H. erinaceus have been
shown to have therapeutic potential for brain and
nerve health.7 The unique neurological activities of
this fungus are the subject of this review.
Hericium erinaceus (lion’s mane, yamabushi-
take, or bearded tooth carpophore) grows on old
or dead broadleaf trees, and is used as both food
and medicine in parts of Asia. The fruiting body
is called hóu tóu gū (“monkey head mushroom”)
in Chinese8 and yamabushitake (“mountain monk
mushroom”) in Japanese. In Chinese and Japanese
medical systems, it has traditionally been used to
fortify the spleen, nourish the gut, and also as an
anticancer drug.9 Lion’s mane is said to be nutri-
tive to the five internal organs (liver, lung, spleen,
heart, and kidney), and promotes good digestion,
general vigor, and strength. It is also recommended
for gastric and duodenal ulcers, as well as chronic
gastritis (in prepared tablet form).10 The mushroom
is also known for its effects on the central nervous
system, and is used for insomnia, vacuity (weak-
ness), and hypodynamia, which are characteristic
symptoms of Qi deficiency in Traditional Chinese
medicine (TCM).
The bioactive metabolites of H. erinaceus can be
classified into high molecular weight compounds,
such as polysaccharides, and low molecular
weight compounds, such as polyketides and
Fungal polysaccharides are found mainly in cell
walls, and are present in large quantities in both
fruiting bodies and cultured mycelium. Hericium
erinaceus fruiting bodies (HEFB) contain immu-
noactive β-glucan polysaccharides, as well as
α-glucans and glucan-protein complexes.12 A total
of more than 35 H. erinaceus polysaccharides
(HEP) have been extracted to date from cultured,
wild-growing, or fermentative mycelia and fresh/
dried fruiting bodies. Of these β-glucans represent
the main polysaccharides. HEP are composed of
xylose (7.8%), ribose (2.7%), glucose (68.4%),
arabinose (11.3%), galactose (2.5%), and mannose
(5.2%).4 Four different polysaccharides isolated
from the H. erinaceus sporocarp show antitumor
activity: xylans, glucoxylans, heteroxyloglucans,
and galactoxyloglucans.5 Chemical analysis shows
that the total content of HEP found in fruiting bod-
ies is higher than that in mycelium. Table 1 lists the
Journal of Restorative Medicine 2017; 6: page 21
Lion’s Mane Neurological Activity
polysaccharides along with their source and chemi-
cal composition.
Studies of the polysaccharides found in
H. erinaceus reveal a number of activities. For
example, extracellular and intracellular polysac-
charides showed a protective effect on oxidative
hepatotoxicity in mice.11 Neuroprotective effects of
HEPs were observed in an in vitro model of cells
that were toxic from amyloid β plaque formation.
In this model, HEPs decreased the production of
reactive oxygen species from 80% to 58% in a dose-
dependent manner, and increased the efficacy of free
radical scavenging. HEPs also promoted cell viabil-
ity and protected cells against apoptosis induced
by amyloid β plaque formation.13 HEPs decreased
blood lactic acid, serum urea nitrogen, tissue glyco-
gen, and malondialdehyde, further supporting the
beneficial role of HEPs on oxidative stress.14
Terpenoids are a class of naturally occurring
hydrocarbons that consist of terpenes attached to an
oxygen containing group. Terpenoids make up over
60% of products in the natural world.15,16
A variety of diterpenes and sesterpenes are found
in the fruiting body and fermenting mycelium of
H. erinaceus.17 Of particular pharmacological inter-
est are two classes of terpenoid compounds thus far
known to occur only in Hericium spp.: hericenones
(C–H), a group of aromatic compounds isolated
from the fruiting body; and erinacines (A–I), a
group of cyathane-type diterpenoids found in the
mycelium.18 Both groups of substances easily cross
the blood-brain barrier, and have been found to have
neurotrophic and in some cases neuroprotective
effects.19 Erinacines (A–I) have demonstrated induc-
tion of nerve growth factor (NGF) synthesis.20 Table
2 lists the terpenoids, sesterpenes, and diterpenoids
along with their source and chemical composition.
Ten erinarols, described as erinarol A–J, five
ergostane-type sterol fatty acid esters, and ten
ergostane-type sterols have been identified in the
fruiting body of H. erinaceus.21 Sterols, such as
Table 1: Polysaccharides: source and composition.
Polysaccharides No. Isolated from Composition
(FI0-a, FI0-a-α, FI0-a-β, FI0-b,
FII-1, FIII-2b)
6Fresh fruiting bodies of H.
Xylans, glucoxylans,
heteroxyloglucans, and
AF2S-2, BF2S-2 2 Fresh fruiting bodies Backbone of β-(l6)-linked
D-glucopyranosyl residues,
and had β-(13) and
β-(l6) glucosidic linkages
Heteropolysaccharides (HEPA1,
3 Mycelium Glucose
Water extractable polysaccharides
(HPA and HPB)
2 Aqueous extract Glucose and galactose
Water soluble polysaccharide
1H. caput-medusae Glucose and galactose
Neutral heteropolysaccharides
(HEP-1 and HEP-4)
2 Fruiting bodies Glucose
Glucans HEP-3 (β-glucan) and
HEP-5 (α glucan)
2 Fruiting bodies Glucose
Acidic polysaccharide (HEP-2) 1 Fruiting bodies Uronic acid
Heteropolysaccharide (HPB-3) 1 The maturating-stage IV,
V, and VI fruiting body
I-fucose, d-galactose and
Homopolysaccharides, a neutral
glucan (HPP)
1 Fermentative mycelia Glucose
Journal of Restorative Medicine 2017; 6: page 22
Lion’s Mane Neurological Activity
ergosterol confer antioxidative properties.21,22
Hericium erinaceus has been found to be the most
potent in vitro inhibitor of both low-density lipo-
protein (LDL) oxidation and HMG Co-A reductase
activity, suggesting therapeutic potential for the
prevention of oxidative stress-mediated vascular
Hericenones and erinacines isolated from
H. erinaceus have demonstrated neuroprotective
properties.24 Hericium erinaceus mycelia (HEM),
and its isolated diterpenoid derivative, erinacine A,
reduced infarction by 22% at 50 mg/kg and 44% at
300 mg/kg in an animal model of global ischemic
stroke. This effect was thought to be partially medi-
ated by its ability to reduce cytokine levels.25
A purified polysaccharide from the liquid culture
broth of HEM was also found to possess neuro-
protective activity in an in vitro model through a
dramatic delay of apoptosis, which was 20%–50%
greater than that seen in the control sample. The
same study showed HEM to be more effective than
control, NGF, or brain-derived neurotrophic fac-
tor (BDNF) alone in enhancing the growth of rat
adrenal nerve cells and neurite (axon or dendrite)
extension.26 However, in a model of NG108-15
neuroblastoma cells subjected to H2O2 oxidative
stress in pre-treatment and co-treatment, the aque-
ous extract of H. erinaceus (as opposed to a purified
polysaccharide), failed to show a protective effect.27
Although it is challenging to draw clinically rele-
vant conclusions from in vitro studies, this suggests
that water extracts would not have a neuroprotec-
tive effect without one particular polysaccharide
being highly concentrated.
The addition of an ethanol extract of HEFB resulted
in NGF gene expression in human astrocytoma
cells, in a concentration-dependent manner. Neurite
outgrowth was also improved. The same investi-
gators also observed that mice fed 5% HEFB dry
powder for 7 days, showed an increase in the level
of NGF mRNA expression in the hippocampus.28
Another study showed that an aqueous extract of
HEFB increased secretion of extracellular NGF
and neurite outgrowth activity. These researchers
also observed a synergistic interaction between
H. erinaceus aqueous extract and exogenous
NGF on neurite outgrowth stimulation of neuro-
blastoma-glioma cells at physiologically relevant
concentrations (1 μg/mL HEFB extract +10 ng/mL
NGF).21 Myelin sheath formation in the presence
of H. erinaceus extract proceeded at a higher rate
and was completed by day 26, as compared to day
31 in controls. No toxic effects of the extracts were
observed in this model.30
In a behavior test on wild-type mice, oral
supplementation with H. erinaceus induced a
Table 2: Sesterpenes and diterpenoids: source and composition.
Terpenoids Isolated from Composition
Fresh fruiting bodies of H. erinaceus
Erinacerins C–L together with
(E)-5- (3,7- methylocta-2,6-dien-
Diterpenoids Fresh fruiting bodies of H. erinaceusErinacines A–I
Isoindolinones Fresh fruiting bodies of H. erinaceusErinaceolactams A–E, hericenone
A, hericenone J, N-De
phenylethylisohericerin, erinacerin A,
and hericerin
Journal of Restorative Medicine 2017; 6: page 23
Lion’s Mane Neurological Activity
statistically significant improvement in spatial
short-term and visual recognition memory.31 In a
double-blind placebo-controlled clinical trial of
50–80-year-old Japanese adults (n=30) diagnosed
with mild cognitive impairment, oral intake of
H. erinaceus 250 mg tablets (96% dry powder)
three times a day for 16 weeks was associ-
ated with marked improvement in the revised
Hasegawa Dementia Scale (HDS-R) as compared
to controls. Scores on the HDS-R decreased,
however, by 4 weeks after cessation of the
In a mouse model of Alzheimer’s disease, oral
administration of HEFB increased expression of
NGF mRNA in the hippocampus, and prevented
impairments of spatial, short-term, and visual
recognition memory induced by amyloid β plaque
that were observed in non-treated mice.28 In another
study using an Alzheimer’s model of mice that
develop amyloid plaque deposits by 6 months of
age, a 30-day oral administration of HEM resulted
in fewer plaque deposits in microglia and astro-
cytes in the cerebral cortex and hippocampus.32
In an aluminum chloride induced animal model
of Alzheimer’s disease, HEM increased serum
and hypothalamic concentrations of acetylcholine
and choline acetyltransferase in a dose-dependent
manner.29 Figure 1 illustrates the apparent mecha-
nisms of action for the effects that H. erinaceus
may have in Alzheimer’s disease.
Oral administration of low-dose HEM (10.76
or 21.52 mg/day) used in an animal model of
Parkinson’s disease led to significant improve-
ment in oxidative stress and dopaminergic lesions
in the striatum and substantia nigra after 25
An aqueous extract of HEFB that was admin-
istered to animals at a dose of 10 mL/kg for
14 days following crush injury improved nerve
regeneration and increased the rate of motor
functional recovery. The animals treated with
HEFB recovered 4–7 days earlier than animals in
the control group, as assessed by walking track
analysis. Normal toe spreading, a measure of
reinnervation, was achieved 5–10 days earlier
in the aqueous extract group than in the control
group. Based on functional evaluation and the
morphological examination of regenerated nerves,
ipsilateral dorsal root ganglia, and target extensor
digitorum longus muscles, researchers concluded
that HEFB aqueous extract promoted peripheral
Figure 1: Mechanism of action of Hericium erinaceus in Alzheimer’s disease.
Journal of Restorative Medicine 2017; 6: page 24
Lion’s Mane Neurological Activity
nerve regeneration with significant functional
As previously described under Cognitive
Function, a double-blind placebo-controlled study
of 50–80-year-old Japanese men and women
(n=30) diagnosed with mild cognitive impair-
ment showed marked improvement in cognitive
function, as measured by the revised Hasegawa
Dementia Scale (HDS-R), when compared to
controls, following oral intake of H. erinaceus
250 mg tablets (96% dry powder) three times
a day for 16 weeks. Scores on the HDS-R
decreased, however, by 4 weeks after cessation of
the intervention.28
In another clinical trial, administration of HEFB
at 2.0 g/day (in cookies) over 4 weeks showed a
reduction in some symptoms of anxiety and depres-
sion in menopausal women (n=30). The Indefinite
Complaints Index categories for Palpitation
and Incentive showed a statistically significant
improvement in women taking HEFB compared to
those taking placebo. The categories of Irritating,
Anxious, and Concentration indicated a trend in the
direction of improvement with HEFB as compared
to placebo.29 Table 3 summarizes the two clinical
trials reported on in this paper.
The recommended dose of H. erinaceus dried
fruiting body for increasing NGF production is
3–5 g per day.34 Hericium erinaceus dosed at
250 mg tablets (96% dry powder) three times a
day for 16 weeks was associated with signifi-
cant improvement on a dementia rating scale in
subjects with mild cognitive impairment.28 The
dose utilized in the study of menopausal women
that showed reduction in symptoms of depression
and anxiety was 2.0 g/day of HEFB (in cookies)
for 4 weeks.29
In an in vitro model, HEFB aqueous extract
demonstrated a remarkable lack of cytotoxicity.31
Toxicology studies of H. erinaceus in rats suggest
that mycelia enriched with 5 mg/g erinacine A at
doses of up to 5 g/kg bodyweight/day are safe. No
toxicity was found in the two clinical trials reported
on here.28,29
No adverse clinical or biochemical events were
reported in the clinical trial of subjects with
mild cognitive impairment.28 In the study of
Table 3: Outcomes of clinical trials of H. erinaceus.
Trial Parameter
Results Adverse events Dose Citation
Mild cognitive
Hasegawa Dementia
Scale (HDS-R)
in cognitive
function scale
None 250 mg tid×16 weeks Mori et al., 200928
Anxiety and
for Epidemiologic
Studies Depression
Scale (CES-D)
and Indefinite
Complaints Index
improvement in
some anxiety and
depression scores
None 2 g/day×4 weeks Nagano et al., 201029
Journal of Restorative Medicine 2017; 6: page 25
Lion’s Mane Neurological Activity
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menopausal women, one subject reported epi-
menorrhea (18 days menorrhea/month). However,
whether or not supplementation with H. eri-
naceus was the cause of the epimenorrhea is
Allergies and sensitivities to mushrooms are not
unusual. One case report describes a 63-year-old
male who suffered acute respiratory failure and
lymphocytosis in his lungs. The report suggests
he had used an extract of dry H. erinaceus (with
no further description given) daily for 4 months
in commonly available doses, and the connection
between the two was considered to be probable. In
another case report, a 53-year-old male exposed to
HEFB occupationally, developed chronic dermatitis
on his hands, with painful fissures within 1 month
of exposure. The dermatitis spread to his forearms,
face, and legs, at which point he ceased exposure
to the HEFB and his symptoms resolved. His
patch tests were negative for the European stan-
dard series, and positive for HEFB. Sensitization
was confirmed by a highly positive repeated open
application test (ROAT) with an aqueous emulsion
of HEFB. Interestingly, patch and prick tests were
negative for other culinary mushrooms suggesting a
lack of cross-sensitivity.
To the best of this author’s knowledge, no toxicity
was established for H. erinaceus in the experimen-
tal, animal, or two clinical trials reported here. The
adverse event (epimenorrhea) reported in one of the
clinical trials could not be conclusively attributed to
the intervention. The substantial historical record for
the traditional use of lion’s mane for chronic ailments,
together with the results of studies so far, suggest
H. erinaceus is safe and has important potential as a
neuroprotective and neurotrophic therapeutic agent
in neurological conditions.35 Its rich myconutrient
composition suggest that using the whole fungus may
be most advantageous clinically. More clinical studies
are needed to corroborate these conclusions.
The authors declare they have no competing interests.
Journal of Restorative Medicine 2017; 6: page 26
Lion’s Mane Neurological Activity
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... Their use for promoting and maintaining a good state of health and the treatment of diseases has been around since ancient times in Asian regions, while in the West, this approach is considerably more recent. Medicinal mushrooms (MMs) are reported to have numerous pharmacological actions such as antimicrobial, anti-inflammatory, immunomodulatory, antidiabetic, cytotoxic, antioxidant, hepatoprotective, anticancer, antioxidant, antiallergic, antihyperlipidemic, and prebiotic properties, among others [2][3][4][5]. These activities are attributable to many bioactive metabolites present in the mycelium but above all in the fruiting body, whose biological effect varies according to the chemical nature and whose distribution varies according to the fungal species. ...
... They are reported to induce nerve growth factor (NGF) synthesis, both in vitro and in vivo. However, this medicinal mushroom also has antioxidative, anti-inflammatory, anticancer, immunostimulant, antidiabetic, antimicrobial, hypolipidemic, and antihyperglycemic properties, although its most frequent use is for the treatment of neurodegenerative diseases and cognitive impairment [4,43,44]. ...
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Medicinal mushrooms have important health benefits and exhibit a broad spectrum of pharmacological activities, including antiallergic, antibacterial, antifungal, anti-inflammatory, antioxidative, antiviral, cytotoxic, immunomodulating, antidepressive, antihyperlipidemic, antidiabetic, digestive, hepatoprotective, neuroprotective, nephroprotective, osteoprotective, and hypotensive activities. The growing interest in mycotherapy requires a strong commitment from the scientific community to expand clinical trials and to propose supplements of safe origin and genetic purity. Bioactive compounds of selected medicinal mushrooms and their effects and mechanisms in in vitro and in vivo clinical studies are reported in this review. Besides, we analyzed the therapeutic use and pharmacological activities of mushrooms.
... Study Type Function/Outcome Measure Reference Ashwagandha (Withania somnifera) in vitro, in vivo, clinical studies antioxidant, anti-inflammatory, blocks Aβ production, inhibits neural cell death, dendrite extension, neurite outgrowth and restores synaptic function, neural regeneration, reverses mitochondrial dysfunction, improves auditory-verbal working memory, executive function, processing speed, and social cognition in patients [20,[23][24][25][26][27][28][29] Brahmi (Bacopa monnieri) in vitro, in vivo, clinical studies antioxidant, anti-inflammatory, improves memory, attention, executive function, blocks Aβ production, inhibits neural cell death, delays brain aging, improves cardiac function [30][31][32][33][34][35][36][37] Cat's claw (Uncaria tomentosa) in vitro, in vivo, pre-clinical studies anti-inflammatory, antioxidant, inhibits plaques and tangles, reduces gliosis, improves memory [38][39][40][41][42][43][44][45] Ginkgo biloba in vitro, pre-clinical, clinical studies antioxidant, improves mitochondrial function, stimulates cerebral blood flow, blocks neural cell death, stimulates neurogenesis [46][47][48][49][50] Gotu kola (Centella asiatica) in vitro, in vivo, clinical studies neuroceutical, cogniceutical, reduces oxidative stress, Aβ levels, and apoptosis, promotes dendritic growth and mitochondrial health, improves mood and memory [51][52][53][54][55][56][57][58] Lion's mane (Hericium erinaceus) in vitro, in vivo, pre-clinical and clinical studies neuroprotective, improves cognition, anti-inflammatory, blocks Aβ production, stimulates neurotransmission and neurite outgrowth [59][60][61][62][63] It is hoped that the historical knowledge base of traditional systems of medicine, coupled with combinatorial sciences and high-throughput screening techniques, will improve the ease with which herbal products and formulations can be used in the drug development process to provide new functional leads for AD. ...
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Background—Alzheimer’s disease (AD) is a multifactorial, progressive, neurodegenerative disease that is characterized by memory loss, personality changes, and a decline in cognitive function. While the exact cause of AD is still unclear, recent studies point to lifestyle, diet, environmental, and genetic factors as contributors to disease progression. The pharmaceutical approaches developed to date do not alter disease progression. More than two hundred promising drug candidates have failed clinical trials in the past decade, suggesting that the disease and its causes may be highly complex. Medicinal plants and herbal remedies are now gaining more interest as complementary and alternative interventions and are a valuable source for developing drug candidates for AD. Indeed, several scientific studies have described the use of various medicinal plants and their principal phytochemicals for the treatment of AD. This article reviews a subset of herbs for their anti-inflammatory, antioxidant, and cognitive-enhancing effects. Methods—This article systematically reviews recent studies that have investigated the role of neuroprotective herbs and their bioactive compounds for dementia associated with Alzheimer’s disease and pre-Alzheimer’s disease. PubMed Central, Scopus, and Google Scholar databases of articles were collected, and abstracts were reviewed for relevance to the subject matter. Conclusions—Medicinal plants have great potential as part of an overall program in the prevention and treatment of cognitive decline associated with AD. It is hoped that these medicinal plants can be used in drug discovery programs for identifying safe and efficacious small molecules for AD.
... The related clinical trial information of mushrooms as a potent neuroprotective effect is still less known. Other researchers presented the related evidence regarding spatial short-term and visual recognition memory, which improves after 16 weeks by taking dried HE fruiting body powder [47]. The oyster mushrooms can be integrated into the Mediterranean diet reported in helping to overcome the risk of AD incidence [48]. ...
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Neurodegenerative diseases (NDs) represent a common neurological pathology that determines a progressive deterioration of the brain or the nervous system. For treating NDs, comprehensive and alternative medicines have attracted scientific researchers' attention recently. Edible mushrooms are essential for preventing several age-based neuronal dysfunctions such as Parkinson's and Alzheimer's diseases. Mushroom such as Grifola frondosa, Lignosus rhinocerotis, Hericium erinaceus, may improve cognitive functions. It has also been reported that edible mushrooms (basidiocarps/mycelia extracts or isolated bioactive compounds) may reduce beta-amyloid-induced neurotoxicity. Medicinal mushrooms are being used for novel and natural compounds that help modulate immune responses and possess anti-cancer, anti-microbial, and anti-oxidant properties. Compounds such as polyphenols, terpenoids, alkaloids, sesquiterpenes, polysaccharides, and metal chelating agents are validated in different ND treatments. This review aims to assess mushrooms' role and their biomolecules utilization for treating different kinds of NDs. The action mechanisms, presented here, including reducing oxidative stress, neuroinflammation, and modulation of acetylcholinesterase activity, protecting neurons or stimulation, and regulating neurotrophins synthesis. We also provide background about neurodegenerative diseases and in-silico techniques of the drug research. High costs associated with experiments and current ethical law imply efficient alternatives with limited cost value. In silico approaches provide an alternative method with low cost that has been successfully implemented to cure ND disorders in recent days. We also describe the applications of computational procedures such as molecular docking, virtual high-throughput screening, molecular dynamic (MD) simulation, quantum-mechanical methods for drug design. They were reported against various targets in NDs.
... Ma et al. 2010;Nagano et al. 2010;Mori et al. 2011;Kim et al. 2014;Phan et al. 2014a Phan et al. , b, 2019Thongbai et al. 2015;Cheng et al. 2016;Kuo et al. 2016;Zhang et al. 2016a;Spelman et al. 2017;Chong et al. 2019;Jang et al. 2019;Kushairi et al. 2019;Saitsu et al. 2019;Üstün and Ayhan 2019;Limanaqi et al. 2020;Yadav et al. 2020). ...
Diversity of wild and cultivated macrofungi as edible and medicinal mushrooms has long been known by humans as a source of valuable food and medicines used by tradipraticians. In the fungal kingdom, macrofungi taxonomically belong to two phyla, the Basidiomycota (class Agaricomycetes) and Ascomycota (class Pezizomycetes). Macrofungi have been used in traditional Asian and European Medicines, and based on 90,000 known worldwide distributed mushroom species, are considered an important resource for modern clinical and pharmacological research. They are regarded as a source of high- and low-molecular-weight bioactive compounds (alkaloids, lipids, phenolics, polysaccharides, proteins, steroids, terpenoids, etc.) with more than 130 therapeutic effects (anti-inflammatory, antimicrobial, antioxidant, antitumor, antiviral, cytotoxic, hepatoprotective, hypocholesterolemic, hypoglycemic, hypotensive, immunomodulatory, etc.). There is also scientific evidence of using macrofungi as neuroprotectants, that is, Agaricus blazei (= Agaricus subrufescens), Ganoderma lucidum, Grifola frondosa, Hericium erinaceus, Pleurotus ostreatus, and Trametes versicolor. However, their neuroprotective effects have not been fully explored. This review discusses recent advances in research on the neuroprotective potential of macrofungi and perspectives for their application as neuroprotectants in biomedicine to prevent, support, or cure neurodegenerative disorders.
... Ma et al. 2010;Nagano et al. 2010;Mori et al. 2011;Kim et al. 2014;Phan et al. 2014a Phan et al. , b, 2019Thongbai et al. 2015;Cheng et al. 2016;Kuo et al. 2016;Zhang et al. 2016a;Spelman et al. 2017;Chong et al. 2019;Jang et al. 2019;Kushairi et al. 2019;Saitsu et al. 2019;Üstün and Ayhan 2019;Limanaqi et al. 2020;Yadav et al. 2020). ...
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Badalyan S.M. et Rapior S. The neurotrophic and neuroprotective potential of macrofungi. In: Medicinal Herbs and Fungi – Neurotoxicity vs. Neuroprotection. Agrawal D.C. et Dhanasekaran M. (Eds). Publisher Springer. Chapter 2: 37-78 (2021). doi:10.1007/978-981-33-4141-8_2 ____ Diversity of wild and cultivated macrofungi as edible and medicinal mushrooms has long been known by humans as a source of valuable food and medicines used by tradipraticians. In the fungal kingdom, macrofungi taxonomically belong to two phyla, the Basidiomycota (class Agaricomycetes) and Ascomycota (class Pezizomycetes). Macrofungi have been used in traditional Asian and European Medicines, and based on 90,000 known worldwide distributed mushroom species, are considered an important resource for modern clinical and pharmacological research. They are regarded as a source of high- and low-molecular-weight bioactive compounds (alkaloids, lipids, phenolics, polysaccharides, proteins, steroids, terpenoids, etc.) with more than 130 therapeutic effects (anti-inflammatory, antimicrobial, antioxidant, antitumor, antiviral, cytotoxic, hepatoprotective, hypocholesterolemic, hypoglycemic, hypotensive, immunomodulatory, etc.). There is also scientific evidence of using macrofungi as neuroprotectants, that is, Agaricus blazei (= Agaricus subrufescens), Ganoderma lucidum, Grifola frondosa, Hericium erinaceus, Pleurotus ostreatus, and Trametes versicolor. However, their neuroprotective effects have not been fully explored. This review discusses recent advances in research on the neuroprotective potential of macrofungi and perspectives for their application as neuroprotectants in biomedicine to prevent, support, or cure neurodegenerative disorders. Corresponding authors:,
... Hericiumerinaceusis an edible and medicinal basidiomycetous mushroom belonging to the family Hericiaceae, order Russulales and class Agaricomycetes [1]. This mushroom is also known as Lion's Mane, Monkey's Mushroom, Bear's Head, Hog's Head Fungus, White Beard, Old Man's Beard, Pom Pom or Bearded Tooth in other parts of the world [2].Hericiumerinaceus has wide and important applications including, anti-hyperglycemic property [3], antibacterial activity [4], antioxidant activity, neurological activity [5] and anticancer activity [6].The mushroom is suitable for bioremediation like in sewage treatment in the pulp and paper industry [7]where it has a high enzymatic activity that facilitates its practical applications. There is an application of lion's mane mushroom culture for commercial scale production of such enzymes as α-amylase, cellulase, β-glucosidase, laccase and xylanase [8]. ...
... The constituents of Antia have previously been shown to possess various neuroregenerative and protective properties. Yamabushitake mushrooms have been shown to synthesize nerve growth factor [51][52][53]; gotsukora extracts reduce the amyloid β levels in the Alzheimer-stricken brains of laboratory animals [23]; diosgenin enhances the cognitive performance of mice [27]; amla acts as a potent antioxidant with strong neuroprotective effects and cognitive enhancement properties [28][29][30][31]; and kothala himbutu protects against deleterious cognitive changes in young diabetic rats [32] and against mercury toxicity in mice hippocampi [33]. Here, Antia is shown to attenuate cognitive dysfunction in the mouse model by targeting several linked pathways, including the amyloidogenic, inflammatory, autophagy, and oxidative stress pathways. ...
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Background: Many neurodegenerative diseases such as Alzheimer's disease are associated with oxidative stress. Therefore, antioxidant therapy has been suggested for the prevention and treatment of neurodegenerative diseases. Objective: We investigated the ability of the antioxidant Antia to exert a protective effect against sporadic Alzheimer's disease (SAD) induced in mice. Antia is a natural product that is extracted from the edible yamabushitake mushroom, the gotsukora and kothala himbutu plants, diosgenin (an extract from wild yam tubers), and amla (Indian gooseberry) after treatment with MRN-100. Methods: Single intracerebroventricular (ICV) injection of streptozotocin (STZ) (3 mg/kg) was used for induction of SAD in mice. Antia was injected intraperitoneally (i.p.) in 3 doses (25, 50, and 100 mg/kg/day) for 21 days. Neurobehavioral tests were conducted within 24 h after the last day of injection. Afterwards, mice were sacrificed and their hippocampi were rapidly excised, weighed, and homogenized to be used for measuring biochemical parameters. Results: Treatment with Antia significantly improved mice performance in the Morris water maze. In addition, biochemical analysis showed that Antia exerted a protective effect for several compounds, including GSH, MDA, NF-κB, IL-6, TNF-α, and amyloid β. Further studies with western blot showed the protective effect of Antia for the JAK2/STAT3 pathway. Conclusions: Antia exerts a significant protection against cognitive dysfunction induced by ICV-STZ injection. This effect is achieved through targeting of the amyloidogenic, inflammatory, and oxidative stress pathways. The JAK2/STAT3 pathway plays a protective role for neuroinflammatory and neurodegenerative diseases such as SAD.
Mushrooms are among the few natural products that have been relied upon for prophylactic and therapeutic applications in human diseases. They have been referred to as forest gems since they can be picked in the wild or better domesticated for appropriate use. Several scientific studies have been conducted to establish claimed potentials or further probe new areas into which mushrooms can find application. Many disciplines, including mycology, microbiology, physiology, chemistry, genetics, and medicine, among others, conduct research on mushrooms. These enable broad and in-depth studies of mushrooms, to include in vitro and in vivo demonstrations of their bioactivity, structural characterization, and isolation of bioactive components. This chapter highlights the bioactive composition of mushrooms by relating structure to bioactivity and demonstrating therapeutic effects on some human diseases using existing literature. The potentials of mushrooms or their products for the treatment or management of diseases, such as tropical illnesses and COVID-19 pandemic, among other issues, have been discussed. Chemistry of bioactive compounds, structure–activity relationships, patents, and analyses of data obtained have been reported and studied for interpretation of results.
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Mushrooms degrade matter to produce metabolite for sustaining life. For degradation they produce enzymes and certain metabolites. Both the enzymes and the metabolites are of use for human. The metabolites have medicinal applications. The traditional use and the scientific work on some traditionally used medicinal mushrooms have been discussed here. Some of the mushrooms are Auricularia delicata, A. polytricha, A. auricular, Agaricus blazei, Coprinus comatus, Cordyceps spp., Fomes fomentarius, Fomitopsis pinicola, Ganoderma lucidum, etc. Auricularia delicata has been used in the traditional medicine of Manipur, India, for dysentery and liver healing therapy. A scientific investigation done by one of the authors on traditionally used Auricularia species showed its hepatoprotective activity. The compound isolated from the ethyl acetate extract was chlorogenic acid. It is known to have hepatoprotective activity. This has been a good example illustrating that traditional medicine is a good lead to drug discovery.
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Hericium erinaceus, an edible and medicinal mushroom, displays various pharmacological activities in the prevention of dementia in conditions such as Parkinson’s and Alzheimer’s disease. The present study explored the neuroprotective effects of H. erinaceus mycelium polysaccharide-enriched aqueous extract (HE) on an l-glutamic acid (l-Glu)-induced differentiated PC12 (DPC12) cellular apoptosis model and an AlCl3 combined with d-galactose-induced Alzheimer’s disease mouse model. The data revealed that HE successfully induced PC12 cell differentiation. A 3 h HE incubation at doses of 50 and 100 µg/mL before 25 mM of l-Glu effectively reversed the reduction of cell viability and the enhancement of the nuclear apoptosis rate in DPC12 cells. Compared with l-Glu-damaged cells, in PC12 cells, HE suppressed intracellular reactive oxygen species accumulation, blocked Ca²⁺ overload and prevented mitochondrial membrane potential (MMP) depolarization. In the Alzheimer’s disease mouse model, HE administration enhanced the horizontal and vertical movements in the autonomic activity test, improved the endurance time in the rotarod test, and decreased the escape latency time in the water maze test. It also improved the central cholinergic system function in the Alzheimer’s mice, demonstrated by the fact that it dose-dependently enhanced the acetylcholine (Ach) and choline acetyltransferase (ChAT) concentrations in both the serum and the hypothalamus. Our findings provide experimental evidence that HE may provide neuroprotective candidates for treating or preventing neurodegenerative diseases.
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Background: There has been a recent upsurge of interest in complementary medicine, especially dietary supplements and foods functional in delaying the onset of age-associated neurodegenerative diseases. Mushrooms have long been used in traditional medicine for thousands of years, being now increasingly recognized as antitumor, antioxidant, antiviral, antibacterial and hepatoprotective agent also capable to stimulate host immune responses. Results: Here we provide evidence of neuroprotective action of Hericium Herinaceus when administered orally to rat. Expression of Lipoxin A4 (LXA4) was measured in different brain regions after oral administration of a biomass Hericium preparation, given for 3 month. LXA4 up-regulation was associated with an increased content of redox sensitive proteins involved in cellular stress response, such as Hsp72, Heme oxygenase -1 and Thioredoxin. In the brain of rats receiving Hericium, maximum induction of LXA4 was observed in cortex, and hippocampus followed by substantia Nigra, striatum and cerebellum. Increasing evidence supports the notion that oxidative stress-driven neuroinflammation is a fundamental cause in neurodegenerative diseases. As prominent intracellular redox system involved in neuroprotection, the vitagene system is emerging as a neurohormetic potential target for novel cytoprotective interventions. Vitagenes encode for cytoprotective heat shock proteins 70, heme oxygenase-1, thioredoxin and Lipoxin A4. Emerging interest is now focussing on molecules capable of activating the vitagene system as novel therapeutic target to minimize deleterious consequences associated with free radical-induced cell damage, such as in neurodegeneration. LXA4 is an emerging endogenous eicosanoid able to promote resolution of inflammation, acting as an endogenous "braking signal" in the inflammatory process. In addition, Hsp system is emerging as key pathway for modulation to prevent neuronal dysfunction, caused by protein misfolding. Conclusions: Conceivably, activation of LXA4 signaling and modulation of stress responsive vitagene proteins could serve as a potential therapeutic target for AD-related inflammation and neurodegenerative damage.
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Background The fruiting body of Hericium erinaceus has been demonstrated to possess anti-dementia activity in mouse model of Alzheimer’s disease and people with mild cognitive impairment. However, the therapeutic potential of Hericium erinaceus mycelia on Alzheimer’s disease remains unclear. In this study, the effects of erinacine A-enriched Hericium erinaceus mycelia (HE-My) on the pathological changes in APPswe/PS1dE9 transgenic mouse model of Alzheimer’s disease are studied. Results After a 30 day oral administration to 5 month-old female APPswe/PS1dE9 transgenic mice, we found that HE-My and its ethanol extracts (HE-Et) attenuated cerebral Aβ plaque burden. It’s worth noting that the attenuated portion of a plaque is the non-compact structure. The level of insulin-degrading enzyme was elevated by both HE-My and HE-Et in cerebral cortex. On the other hand, the number of plaque-activated microglia and astrocytes in cerebral cortex and hippocampus were diminished, the ratio of nerve growth factor (NGF) to NGF precursor (proNGF) was increased and hippocampal neurogenesis was promoted after these administrations. All the mentioned benefits of these administrations may therefore improve the declined activity of daily living skill in APPswe/PS1dE9 transgenic mice. Conclusions These results highlight the therapeutic potential of HE-My and HE-Et on Alzheimer’s disease. Therefore, the effective components of HE-My and HE-Et are worth to be developed to become a therapeutic drug for Alzheimer’s disease.
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Background Hericium erinaceus (HE) is a well-known mushroom in traditional Chinese food and medicine. HE extracts from the fruiting body and mycelia not only exhibit immunomodulatory, antimutagenic and antitumor activity but also have neuroprotective properties. Here, we purified HE polysaccharides (HEPS), composed of two high molecular weight polysaccharides (1.7 × 105 Da and 1.1 × 105 Da), and evaluated their protective effects on amyloid beta (Aβ)-induced neurotoxicity in rat pheochromocytoma PC12 cells. Methods HEPS were prepared and purified using a 95 % ethanol extraction method. The components of HEPS were analyzed and the molecular weights of the polysaccharides were determined using high-pressure liquid chromatography (HPLC). The neuroprotective effects of the polysaccharides were evaluated through a 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and an MTT assay and by quantifying reactive oxygen species (ROS) and mitochondrial membrane potentials (MMP) of Aβ-induced neurotoxicity in cells. Result Our results showed that 250 μg/ml HEPS was harmless and promoted cell viability with 1.2 μM Aβ treatment. We observed that the free radical scavenging rate exceeded 90 % when the concentration of HEPS was higher than 1 mg/mL in cells. The HEPS decreased the production of ROS from 80 to 58 % in a dose-dependent manner. Cell pretreatment with 250 μg/mL HEPS significantly reduced Aβ-induced high MMPs from 74 to 51 % and 94 to 62 % at 24 and 48 h, respectively. Finally, 250 μg/mL of HEPS prevented Aβ-induced cell shrinkage and nuclear degradation of PC12 cells. Conclusion Our results demonstrate that HEPS exhibit antioxidant and neuroprotective effects on Aβ-induced neurotoxicity in neurons.
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The protective effects of extracellular and intracellular polysaccharides from Hericium erinaceus SG-02 on the CCl4-induced hepatic injury of mice were investigated in this work. By the analysis of GC, the extracellular polysaccharides (EPS) were composed of arabinose, mannose, galactose, and glucose with a ratio of 1:7:14:52, and the composition of intracellular polysaccharides (IPS) was rhamnose, xylose, mannose, galactose, and glucose with a ratio of 3:4:7:14:137. The model of hepatic injury of mice was induced by CCl4 and three tested levels (200, 400, and 800 mg/kg) of EPS and IPS were set as the experimental group. Results showed that the aspartate aminotransferase and glutamic pyruvic transaminase activities in serum were reduced by the supplement of EPS and IPS, while the blood lipid levels including cholesterol, triglyceride, and albumin were improved. In liver tissue, the lipid peroxidation and malondialdehyde were largely decreased, and the superoxide dismutase and catalase activities were significantly increased. The evidence demonstrated that the EPS and IPS of H. erinaceus SG-02 were protective for liver injury. The histopathological observations of mice liver slices indicated that EPS and IPS had obvious effects on liver protection.
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Hericium erinaceus is an edible mushroom; its various pharmacological effects which have been investigated. This study aimed to demonstrate whether efficacy of oral administration of H. erinaceus mycelium (HEM) and its isolated diterpenoid derivative, erinacine A, can act as an anti-neuroinflammatory agent to bring about neuroprotection using an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinson’s disease, which results in motor disturbances, in addition to elucidating the mechanisms involved. Mice were treated with and without HEM or erinacine A, after MPTP injection for brain injuries by the degeneration of dopaminergic nigrostriatal neurons. The efficacy of oral administration of HEM improved MPTP-induced loss of tyrosine hydroxylase positive neurons and brain impairment in the substantia nigra pars compacta as measured by brain histological examination. Treatment with HEM reduced MPTP-induced dopaminergic cell loss, apoptotic cell death induced by oxidative stress, as well as the level of glutathione, nitrotyrosine and 4-hydroxy-2-nonenal (4-HNE). Furthermore, HEM reversed MPTP-associated motor deficits, as revealed by the analysis of rotarod assessment. Our results demonstrated that erinacine A decreases the impairment of MPP-induced neuronal cell cytotoxicity and apoptosis, which were accompanied by ER stress-sustained activation of the IRE1α/TRAF2, JNK1/2 and p38 MAPK pathways, the expression of C/EBP homologous protein (CHOP), IKB-β and NF-κB, as well as Fas and Bax. These physiological and brain histological changes provide HEM neuron-protective insights into the progression of Parkinson’s disease, and this protective effect seems to exist both in vivo and in vitro.
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DOI 10.1007/s11557-015-1105-4. Online Medicinal mushrooms have become a compelling topic because the bioactive compounds they contain promise a plethora of therapeutic properties. Hericium erinaceus commonly known as “Houtou” or “Shishigashira” in China and “Yamabushitake” in Japan, has commonly been prescribed in Traditional Chinese Medicine (TCM), because its consumption has been shown to be beneficial to human health. The species is found throughout the northern hemisphere in Europe, Asia, and North America. Hericium erinaceus has been firmly established as an important medicinal mushroom and its numerous bioactive compounds have been developed into food supplements and alternative medicines. However, the correspondence of the active components that cause the observed effects is often not clear. The mushroom as well as the fermented mycelia have been reported to produce several classes of bioactive molecules, including polysaccharides, proteins, lectins, phenols, and terpenoids. Most interestingly, two classes of terpenoid compounds, hericenones and erinacines, from fruiting bodies and cultured mycelia, respectively, have been found to stimulate nerve growth factor (NGF) synthesis. In this review we examine the scientific literature to explore and highlight the scientific facts concerning medicinal properties of H. erinaceus. We provide up-to-date information on this mushroom, including its taxonomy and a summary of bioactive compounds that appear related to the therapeutic potential of H. erinaceus. See
2nd edition of the first book on the topic published in North America. The first edition was self-published in October, 1986. An exploration of tradition, healing, and culture. Covers the history of the uses of fungi for healing, including nutritional value, summary of cultural uses, history, and science on over 100 species. Shamanistic uses of hallucinogenic fungi. Botanica Press Imprint, published by The Book Publishing Co., Summertown, TN. 251 pp. with illustrations.
Hericium erinaceus (Bull.) Pers., also known as Yamabushitake, Houtou and Lion’s Mane, is capable of fortifying the spleen and nourishing the stomach, tranquilizing the mind, and fighting cancer. Over the past decade, it has been demonstrated that H. erinaceus polysaccharides possess various promising bioactivities, including antitumor and immunomodulation, anti-gastric ulcer, neuroprotection and neuroregeneration, anti-oxidation and hepatoprotection, anti-hyperlipidemia, anti-hyperglycemia, anti-fatigue and anti-aging. The purpose of the present review is to provide systematically reorganized information on extraction and purification, structure characteristics, biological activities, and industrial applications of H. erinaceus polysaccharides to support their therapeutic potentials and sanitarian functions.