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Lion's Mane Mushroom
(AKA Yamabushitake or H. erinaceum )
Research
https://www.ncbi.nlm...pubmed/24506286
Teng F1, Bito T, Takenaka S, Yabuta Y, Watanabe F.
Lion's Mane Mushroom (LMM) contains Vitamin B12.

https://www.ncbi.nlm...pubmed/16782550
Son CG1, Shin JW, Cho JH, Cho CK, Yun CH, Chung W, Han SH.
Hericium erinaceum is a medicinal and edible mushroom with anti-microbial and anti-cancer activities.

https://www.ncbi.nlm...pubmed/25676326
Noh HJ1, Yang HH2,3, Kim GS1, Lee SE1, Lee DY1, Choi JH1, Kim SY1, Lee ES1, Ji SH1, Kang KS4, Park HJ5, Kim JR2,3, Kim KH6.
Six compounds were isolated and identified as hericenone D (1), (22E,24R)-5α,8α-epidioxyergosta-6,22-dien-3β-ol (2), erinacerin B (3), hericenone E (4), hericenone F (5) and isohericerin (6) by comparing their spectroscopic data with previously reported values.
https://www.ncbi.nlm...pubmed/29498678
He J1, Fan P2, Feng S3, Shao P4, Sun P5.
two isoflavones were identified as genistein (4',5,7-trihydroxyisoflavone, C15H10O₅) and daidzein (4',7-dihydroxyisoflavone, C15H10O₄),

https://www.ncbi.nlm...pubmed/20380848
Xu H1, Wu PR, Shen ZY, Chen XD.
H. erinaceum polysaccharides significantly enhanced skin antioxidant enzymes, MMP-1, TIMP-1 activities and collagen protein levels in a dose-dependent manner. It can be concluded that H. erinaceum polysaccharides possess anti-skin-aging activities.

https://www.ncbi.nlm...pubmed/26559695
Mori K1, Ouchi K1, Hirasawa N2.
Our findings indicate the possibility that H. erinaceus exerts anti-inflammatory effects on macrophages through the inhibition of TLR4-JNK signaling and prevents or ameliorates adipose tissue inflammation associated with obesity.

https://www.ncbi.nlm...pubmed/23510212
Wong KH1, Naidu M, David RP, Bakar R, Sabaratnam V.
Daily oral administration of H. erinaceus could promote the regeneration of injured rat peroneal nerve in the early stage of recovery.

https://www.ncbi.nlm...pubmed/27481156
Qin M1, Geng Y1, Lu Z1, Xu H1, Shi JS1, Xu X2, Xu ZH3.
Anti-inflammatory, a protective agent in the treatment of IBDs (inflammatory bowel disease) and Ulcerative Colitis.

https://www.ncbi.nlm...pubmed/29199560
Liu PS1, Chueh SH2, Chen CC3, Lee LY4, Shiu LY4.
This study demonstrates novel characteristics of H. erinaceus in reducing nociceptive (pain) behavior and blocking the functional activity of P2R (calcium binding receptors).

https://www.ncbi.nlm...pubmed/28085076
Li W1, Lee SH2, Jang HD3, Ma JY4, Kim YH5.
These results suggested that H. erinaceum could be utilized in the development of natural antioxidant and anti-osteoporotic (fights osteoporosis) nutraceuticals and functional foods.

https://www.ncbi.nlm...les/PMC5237458/
Federico Brandalise, 1 Valentina Cesaroni, 2 Andrej Gregori, 3 Margherita Repetti, 2 Chiara Romano, 2 Germano Orrù, 4 Laura Botta, 2 Carolina Girometta, 5 Maria Lidia Guglielminetti, 5 , 6 Elena Savino, 5 , 6 and Paola Rossi 2 , 6 ,
In wild-type mice the oral supplementation with H. erinaceus induces, in behaviour test, a significant improvement in the recognition memory and, in hippocampal slices, an increase in spontaneous and evoked excitatory synaptic current in mossy fiber-CA3 synapse. In conclusion, we have produced a series of findings in support of the concept that H. erinaceus induces a boost effect onto neuronal functions also in nonpathological conditions.

https://www.ncbi.nlm...les/PMC5133811/
Junrong Zhang,1 Shengshu An,1 Wenji Hu,1 Meiyu Teng,1 Xue Wang,1 Yidi Qu,1 Yang Liu,1 Ye Yuan,2 and Di Wang1,
Our findings provide experimental evidence that HE (H. erinaceus) may provide neuroprotective candidates for treating or preventing neurodegenerative diseases.

https://www.ncbi.nlm...les/PMC4895996/
Jai-Hong Cheng, Chia-Ling Tsai, Yi-Yang Lien, Meng-Shiou Lee, and Shyang-Chwen Sheu
Our results demonstrate that HEPS exhibit antioxidant and neuroprotective effects on Aβ-induced neurotoxicity in neurons.

https://www.ncbi.nlm...les/PMC4415743/
Lijun Hao, 1 Yuxi Xie, 2 , * Guikai Wu, 1 Aibin Cheng, 2 Xiaogang Liu, 3 Rongjuan Zheng, 1 Hong Huo, 1 and Junwei Zhang 2
We observed that HE supplementation could restrain the hepatic (liver) damage caused by acute alcohol exposure.

https://examine.com/.../yamabushitake/
Yamabushitake, known as the Lion's Mane Mushroom, is a dietary mushroom that can be a supplement.
As the water soluble extract seems to be less potent than other fractions, it may be best to take Yamabushitake with meals if in supplemental form.
If itchy skin occurs, this may be related to an increase in Nerve Growth Factor and unless accompanied by signs of allergy should be benign.
Currently, the only human study has used an oral dose of 1,000mg Yamabushitake (96% purity extract) thrice daily for a cumulative total of 3,000mg extract. While it is unknown if this is the optimal dose or not, it appeared to be effective.
Yamabushitake has been noted to increase mRNA expression of nerve-growth factor (NGF) (Nerve growth factor is primarily involved in the regulation of growth, maintenance, proliferation, and survival of certain target nerve cells.) in isolated astrocytes to around 5-fold that of control at 100-150ug/mL of the ethanolic extract in a concentration dependent manner, with no efficacy noted in the water extract
An increase in NGF mRNA has been detected in the hippocampus, but not cortex, of mice given 5% of the diet as yamabushitake for a period of seven days to around 1.3-fold of control. (Note - Interesting as Cymbalta heavily afects the hippocampus).
Neuronal excitability from glutamic acid appears to be attenuated in the presence of yamabushitake extracts.
Anxiety and Depressive symptoms have also been reduced in humans fed 2g of Yamabushitake, via cookies, over the course of 4 weeks. There was a significant difference between groups on the measurements of concentration and irritability, favoring the Yamabushitake group. Nagano M, et al. Reduction of depression and anxiety by 4 weeks Hericium erinaceus intake. Biomed Res. (2010)
Yamabushitake may act as a PPARα agonist and reduce triglycerides without any apparent effect on cholesterol.
Although both the hot water and ethanolic extracts have been found inactive on cholesterol and HDL-C, an extract derived from the mycelium of yamabushitake (ethanolic extract which was then lyophilized) appeared to reduce LDL by 45.5% and improve HDL-C by 31.1% when taken at an oral dose of 200mg/kg with 50mg/kg also being somewhat active
Side Effects
There has been one case study of a 63 year old man who suffered acute respiratory failure, and the excess lymphocytes in his lungs showed high reactivity to Yamabushitake daily for 4 months in dosages commonly bought. The connection between the two, when rated, is seen as a 'probably' connection

https://nootropicsex...e/#dosage-notes
Dosage
Dosing of Lion’s Mane Mushroom depends on the strength of the extract. It’s available in capsule or powder form.
For Lion’s Mane 10:1 extract (30% polysaccharide), daily dosage is 500 – 1,000 mg taken 1 to 3 times per day.
Other retail extract dosage of Lion’s Mane ranges from 300 mg to 3000 mg dosed 1 – 3 times per day. Check the label and see what the manufacturer recommends. And when first using the supplement, start with the lowest dose and see how your body reacts.
Start at 500 mg per day and see how it works for you. If you don’t experience a benefit, boost Lion’s Mane in small increments of 250 mg per day until you notice an improvement.

Side Effects
Lion’s Mane Mushroom is non-toxic and considered very safe. So there are very few side effects reported.
Some neurohackers report itchy skin from higher doses. Likely attributable to a boost in Nerve Growth Factor.
Lion’s Mane has been tested in animals showing no side effects or toxicity even up to 5 grams per kilogram.

https://www.cabdirec...act/20103302738
Our results show that H. erinaceum intake has the possibility to reduce depression and anxiety.

https://www.omicsonl...0.php?aid=40841
Blaz Gerbec1, Eva Tavčar2, Andrej Gregori3, Samo Kreft2and Marin Berovic1*
Erinacine A, isolated from the cultured mycelia of H. erinaceum, the main representative of this compounds group, has a strong enhancing effect on NGF synthesis (Nerve growth factor is a neuropeptide involved in the regulation of growth, maintenance, proliferation, and survival of certain target nerve cells) much stronger than epinephrine. Furthermore, this compound increases catecholamine and NGF content in the central nervous system of rats.

Erinacines and hericenons reduce anxiety as well as depression. For an accurate understanding of the overall mechanism of H. erinaceus diterpenoids action it requires additional clinical studies with physiological markers, such as hormones, or more profounded studies of autonomic nervous activity

Mori K, et al. Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human astrocytoma cells . Biol Pharm Bull. (2008)
Yamabushitake has been noted to increase mRNA expression of nerve-growth factor (NGF). An increase in NGF mRNA has been detected in the hippocampus, but not cortex, of mice given 5% of the diet as yamabushitake for a period of seven days to around 1.3-fold of control.

Neurotropic and Trophic Action of Lion's Mane Mushroom Hericium erinaceus (Bull.: Fr.) Pers. (Aphyllophoromycetideae) Extracts on Nerve Cells in Vitro .
When looking at neurons specifically, yamabushitake appears to promote nerve cell life span and formation of myelin. (Myelin insulates the nerve cells to increase the speed at which information (electrical signals) travels from one nerve cell body to another.)
Reduces neuronal (nerve cell) excitability from glutamic acid in the presence of yamabushitake extracts.

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Kolotushkina EV, et al. The influence of Hericium erinaceus extract on myelination process in vitro . Fiziol Zh. (2003)
It has also been shown, in vitro, to enhance myelination (production of myelin sheath) of neurons, which may be downstream of NGF.

Ueda K, et al. An endoplasmic reticulum (ER) stress-suppressive compound and its analogues from the mushroom Hericium erinaceum . Bioorg Med Chem. (2008)
An analogue of the Hericenones, called 3-hydroxyhericenone, has been implicated in preserving neurons from death induced by endoplasmic reticulum stress

https://www.thefreel...on.-a0430893147
Summary of the antianxiety/antidepressive effects of components of H. erinaceus.

Mori K, et al. Effects of Hericium erinaceus on amyloid β(25-35) peptide-induced learning and memory deficits in mice . Biomed Res. (2011)
Yamabushitake appears to protect rats against cognitive decline caused by β-amyloid pigmentation at the same 5% of the diet seen previously.

Mori K, et al. Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial . Phytother Res. (2009)
One human study using 3g of 98% Yamabushitake powder (in capsule form) showed significantly improvements on a rating scale of dementia in persons suffering from general cognitive decline. The supplement increased cognition (the mental action or process)relative to control, and the degree of improvement increased with time; however, 4 weeks after cessation saw the start of a decline back to normal despite still being significantly elevated above control.

Nagano M, et al. Reduction of depression and anxiety by 4 weeks Hericium erinaceus intake . Biomed Res. (2010)
Anxiety and Depressive symptoms have also been reduced in humans fed 2g of Yamabushitake, via cookies, over the course of 4 weeks. There was a significant difference between groups on the measurements of concentration and irritability, favoring the Yamabushitake group.

Abdullah N, et al. Evaluation of Selected Culinary-Medicinal Mushrooms for Antioxidant and ACE Inhibitory Activities . Evid Based Complement Alternat Med. (2012)
Yamabushitake appears to be an ACE inhibitor (hot water extract of the fruiting bodies)
*An angiotensin-converting-enzyme inhibitor (ACE inhibitor) is used primarily for the treatment of elevated blood pressure and congestive heart failure.


Hiwatashi K, et al. Yamabushitake mushroom (Hericium erinaceus) improved lipid metabolism in mice fed a high-fat diet . Biosci Biotechnol Biochem. (2010)
Both a hot water and ethanolic extract of yamabushitake have been tested in hyperlipidemic mice at 2% of the diet (1.896-3.16g/kg hot water and 2.016-3.36g/kg ethanolic) is able to reduce triglycerides (8% hot water and 27.1% ethanolic relative to control) without any apparent effect on HDL-C nor total cholesterol.

Hiwatashi K, et al. Yamabushitake mushroom (Hericium erinaceus) improved lipid metabolism in mice fed a high-fat diet . Biosci Biotechnol Biochem. (2010)
AND
Yang BK, Park JB, Song CH. Hypolipidemic effect of an Exo-biopolymer produced from a submerged mycelial culture of Hericium erinaceus . Biosci Biotechnol Biochem. (2003)
Although both the hot water and ethanolic extracts have been found inactive on cholesterol and HDL-C, an extract derived from the mycelium of yamabushitake (ethanolic extract which was then lyophilized) appeared to reduce LDL by 45.5% and improve HDL-C by 31.1% when taken at an oral dose

Kim YO, et al. Hericium erinaceus suppresses LPS-induced pro-inflammation gene activation in RAW264.7 macrophages . Immunopharmacol Immunotoxicol. (2011)
Yamabushitake has been noted to suppress LPS-induced macrophage activation.
* Microphage is a type of white blood cell that engulfs and digests cellular debris, foreign substances, microbes, cancer cells,


Lee JS, et al. Study of macrophage activation and structural characteristics of purified polysaccharides from the fruiting body of Hericium erinaceus . J Microbiol Biotechnol. (2009)
The polysaccharide known as HEF-AP Fr II (a beta-glucan), conversely, has been found to stimulate macrophage activity itself

Wang JC, et al. Antitumor and immunoenhancing activities of polysaccharide from culture broth of Hericium spp . Kaohsiung J Med Sci. (2001)
increase in macrophage and T-cell count seen with incubations of this mushroom.
*A T cell, or T lymphocyte, is a type of white blood cell, fights cancer)

Kim SP, Nam SH, Friedman M. Hericium erinaceus (Lion's Mane) mushroom extracts inhibit metastasis of cancer cells to the lung in CT-26 colon cancer-tansplanted mice . J Agric Food Chem. (2013)
hot water and ethanolic extracts of yamabushitake show anti-metastatic potential in CT-26 colon cancer cells at 500µg/mL associated with less ERK and JNK phosphorylation which resulted in less MMP secretion and lamellipodia formation.
Both the hot water and ethanolic extracts of yamabushitake appear to inhibit metastasis of colon cancer cells to the lung by 66-69% with 10mg/kg injections of extracts made of the fruiting bodies

Abdulla MA, et al. Potential activity of aqueous extract of culinary-medicinal Lion's Mane mushroom, Hericium erinaceus (Bull.: Fr.) Pers. (Aphyllophoromycetideae) in accelerating wound healing in rats . Int J Med Mushrooms. (2011)
Yamabushitake is associated with increasing the rate of repair of flesh wounds when the water extract is applied to the wound.\l "

BK Yang et al., “Hypolipidemic effect of an Exo-biopolymer produced from a submerged mycelial culture of Hericium erinaceus," Bioscience, Biotechnology, and Biochemistry, vol. 67, no. 6 (June 2003): 1292–1298.
A cell wall polysaccharide produced by a special, submerged culture of lion’s mane mushroom was found in an animal study to lower cholesterol by 32%, LDL cholesterol by 45.4%, and triglycerides by 34.3%, and to raise the “good” HDL cholesterol by 31%. The researchers proposed that the mushroom’s constituents helped to lower cholesterol production via the hepatic HMG-CoA reductase pathway, reducing the amount of this enzyme by 20%.

https://www.tandfonl...37.2015.1042525
The results suggested that L. brevis HP2 and L. fermentum HP3 are good starter cultures for H. erinaceus fermentation with enriched GA and GABA production. In this case, GA production was significantly influenced by K2HPO4, pH and temperature whereas GABA production was significantly influenced by pH and temperature.

https://www.research..._tbl2_324253170

See table 2 for content of amino acids and especially GABA and Glutamate.

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Active ingredients
Hericium erinaceus (Lion's Mane Mushroom) contains a number of active compounds such as ...

Beta-glucan (Polysaccarides)
β-glucan decreases blood levels of ldl cholesterol

Hericenones
promote nerve growth factor synthesis, they are are cyathane metabolites
Hericenone A
Hericenone B
Hericenone B appears to potently and specifically inhibit collagen-induced platelet aggregation, may bhe used to avoid developing blood clots (thrombosis)
Hericenone C
Hericenone D
Hericenone E
Hericenone F
Hericenone G
Hericenone H
Hericenone J
Isohericenone J
Anticancer activity

Hericenone K
Isohericerin
Anticancer activity

N-De phenylethyl isohericerin
4-[3',7'-dimethyl-2',6'-octadienyl]-2-formyl-3-hydroxy-5-methyoxybenzylalcohol
hericerin A
3-hydroxyhericenone
BACE1-inhibitor (BACE1 is an aspartic-acid protease important in the formation of mylen sheaths in peripheral nerve cells) Drugs to block this enzyme (BACE inhibitors) in theory would prevent the buildup of beta- amyloid and may help slow or stop Alzheimers disease.
has been implicated in preserving neurons from death induced by endoplasmic reticulum stress.
a promising naturally occurring chemical constituent for the treatment of Alzheimer's disease via the inhibition of the β-secretase enzyme.

3,4-dihydro-5-methoxy-2-methyl-2-(40-methyl-20-oxo-30-pentenyl)-9(7H)- oxo-2H-furo[3,4-h]benzopyran
Anticancer activity

Heteroglucans
Heterooxylans
Erinacines
Erinacines A, B and C, strong stimulators of nerve growth factor (NGF)-synthesis, from the mycelia of Hericium erinaceum .
isolated erinacines (A-C) are known to stimulate NGF secretion at 1mM concentrations, with a potency greatly exceeding that of adrenaline at the same concentrations.

Erinacines A-K, P, and Q are subjects of pharmacological research.
Erinacine A - enhancing effect on nerve growth factor synthesis and it also increases catecholamines and shows anticancer activity.
erinacines (A-C) are known to stimulate NGF secretion
Erinacine E - a kappa opiod receptor agonist, analgesic, hallucinogenis, used to treat depression in some addictions, mania, bipolar and high dopamine levels. Increases memory recall. It is a diuretic, neuroprotective against hypoxia/ischemia and can cause euphoria.
Erinacines H - Erinacine H showed stimulating activity of nerve growth factor (NGF)-synthesis.
Erinacine I -
isoericerin
(22E,24R)-5α,8α-epidioxyergosta-6,22-dien-3β-ol (2), erinacerin B
Sterols
Cerevisterol 6-cinnamate -could be utilized in the development of natural antioxidant and anti-osteoporotic nutraceuticals (11 compounds in LMM are antioxidant and anti-osteoporotic"
ergosterol
Ergosterol is a provitamin form of vitamin D2; exposure to ultraviolet (UV) light causes a chemical reaction that produces vitamin D2.

beta-sitosterol
β-sitosterol is being studied for its potential to reduce benign prostatic hyperplasia (prostate enlargement) (BPH) and blood cholesterol levels.

Iisoflavones
genistein
Inhibits the growth of new blood vessels and a phytoestrogn. Besides functioning as an antioxidant and expelling parasites and have been shown to interact with estrogen receptors, causing effects in the body similar to those caused by the hormone estrogen.
Genistein influences multiple biochemical functions in living cells:
⦁ agonist of GPER (estrogen receptor)
⦁ activation of peroxisome proliferator-activated receptors (PPARs)
activation of peroxisome proliferator-activated receptors (PPARs) They are used for the treatment of symptoms of metabolic syndrome, mainly for lowering triglycerides and blood sugar.

⦁ inhibition of several tyrosine kinases
Numerous tyrosine kinases inhibitors aiming at various tyrosine kinases have been generated by the originators of these compounds and proven to be effective anti-tumor agents and anti-leukemia agents
⦁ inhibition of topoisomerase. Active in DNA reproduction. Used as an anticancer agent.
⦁ inhibition of AAAD ((inhibits the synthesis of dopamine)
⦁ direct antioxidation with some proxidative features
⦁ activation of NRF2 antioxidative response (causes the DNA production of leucine.)
⦁ stimulation of autophagy ((is the natural, regulated mechanism of the cell that disassembles unnecessary or dysfunctional components)
⦁ inhibition of the mammalian hexose transporter (Hexaose - a sugar)
⦁ contraction of several types of smooth muscles
⦁ modulation of CFTR channel, potentiating its opening at low concentration and inhibiting it a higher doses. Related to gene mutations which cause cystic fibrosis and other related conditions.
⦁ inhibition of cytosine methylation
⦁ inhibition of DNA methyltransferase
⦁ inhibition of the glycine receptor. One of the most widely distributed inhibitory receptors in the central nervous system and has important roles in a variety of physiological processes, especially in mediating inhibitory neurotransmission in the spinal cord and brainstem.
⦁ inhibition of the nicotinic acetylcholine receptors. Nicotinic acetylcholine receptors are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs, including the nicotinic receptor agonist nicotine.

daidzein
In humans, recent research has shown the viability of using daidzein in medicine for menopausal relief, osteoporosis, blood cholesterol, and lowering the risk of some hormone-related cancers, and heart disease.

Erinarols A-F
Ergostane-type sterol fatty acid esters
Herinase
Erinaceolactams A-E
Lectins
A lectin designated as Hericium erinaceum agglutinin (HEA)
Sialic-acid binding lectin
Orcinol derivatives (Mycelium)
blazein
3β,5α-dihydroxy-6β-acetoxy-ergosta-7,22-diene
ergosta-7,22-diene-3β,5α,6α-triol


https://pubs.acs.org...acs.joc.7b00920
Isohericerin, isohericenone, and erinacerin A have all been synthesized.

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https://www.scienced...221169117310390
Anti-hyperglycemic property of Hericium erinaceus – A mini review

Abstract
Hericium erinaceus (H. erinaceus) is one of the widely used edible mushrooms around the world, primarily in Asian countries. H. erinaceus is used in traditional medicines, and mushroom based foods. The fruiting body and mycelia of H. erinaceus are extracted using the solvents, and several bioactive compounds were identified. Several studies have reported that those bioactive compounds exhibit many health benefits such as hemagglutinating, antimicrobial, immunomodulatory, antitumor, antioxidant, and anti-aging activities, etc. This manuscript consciously updated the information about the composition of H. erinaceus, H. erinaceus based foods, and anti-hyperglycemic property of H. erinaceus.

1. Introduction
Edible mushrooms are one of the acceptable functional foods for human and are being used for several hundred years. Mushrooms are known for its texture, flavor, and health-promoting property [1], [2]. Especially, mushrooms are a rich source of all essential amino acids that are required by the human beings. They are considered as a healthy food because of its enriched protein and dietary fiber content with low calories and fat [3]. Thus far, more than two thousand mushrooms species have been reported [4], [5]. Edible mushrooms have been screened and studied for several medicinal properties like anticancer, and antimicrobial activities. Moreover, mushrooms were used as alternative food based medicines [6], [7].
Hericium erinaceus (H. erinaceus) is one of the well-studied edible and medicinal mushrooms that belongs to family Hericiaceae, order Russulales, and class Agaricomycetes. H. erinaceus has a prominent place in Chinese traditional medicine, and information about H. erinaceus is available in European and South American literature [8]. The fruiting body and mycelia of H. erinaceus have been reported for its several pharmacological actions, such as hemagglutinating, antimicrobial, immunomodulatory, antitumor, antioxidant, and anti-aging activities [9], [10], [11], [12], [13], [14].
This manuscript summarizes the nutritional composition of H. erinaceus and recent developments on H. erinaceus based functional foods and scientific reports about the hypoglycemic property of H. erinaceus.

2. Composition of H. erinaceus
The chemical composition and bioactive compounds of fruit bodies and mycelia of H. erinaceus have been reported by several researchers. H. erinaceus contains structurally diverse compounds, and about seventy different secondary metabolites were estimated. Hericerins [aromatic compounds such as hericerin A, isohericenone J, isoericerin, hericerin, N-dephenylethyl isohericerin, hericenone J, 4-(3′,7′-dimethyl-2′,6′-octadienyl)-2-formyl-3-hydroxy-5-methoxybenzylalcohol, erinacene D, resorcinols, erinacerins, and hericenols], erinacines (erinacine A, and diterpenoids), erinacerins-isoindolin-1-ones (erinacerins C-L), erinaceolactones, glycoprotein (H. erinaceus polysaccharide-protein-5), polysaccharides (β-D-glucans), sterols (ergosterol, and erinarols G-J), vitamin B12 lactone (c-lactone), and volatile compounds (2-methyl-3-furanthiol, 2-ethylpyrazine, and 2,6-diethylpyrazine) have been reported to be present in the H. erinaceus. The health promoting ability of H. erinaceus is attributed to these chemical substances (Table 1).

Table 1. Composition and bioactivities of H. erinaceus.
S. No. Compounds Bioactivities Refs
1 Hericerins
Hericerin A, Isohericenone J, Isoericerin, Hericerin, N-dephenylethyl isohericerin, Hericenone J, 4-(3′,7′-dimethyl-2′,6′-octadienyl)-2-formyl-3-hydroxy-5-methoxybenzylalcohol, Erinacene D, Resorcinols, Erinacerins, and Hericenols. Anticancer [39], [40], [41], [42], [43]
2 Erinacines
Erinacine A
Diterpenoids Neuroprotective [44], [45]
3 Erinacerins-Isoindolin-1-ones
Erinacerins C-L Anticancer [46]
4 Erinaceolactones Plant growth
regulatory activity [47]
5 Glycoprotein
H. erinaceus polysaccharide-protein
(HEG-5) Hemagglutinating activity, Inhibit gastric carcinoma. [48]
6 Polysaccharides
β-D-glucans Immune modulation [49], [50], [51], [52]
7 Sterols
Ergosterol
Erinarols G-J Anti-inflammatory, antiproliferative [41], [49], [53]
8 Vitamin B12 Lactone
c-lactone Inactive [54]
9 Volatile Compounds
2-methyl-3-furanthiol, 2-ethylpyrazine, 2,6-diethylpyrazine Antimicrobial [55], [56], [57]

 

3. H. erinaceus based functional foods
It is known that the dried powder of H. erinaceus fruiting body confined with protein (20%), carbohydrate (61%), fat (5%), ash (7%), amino acids (14.3 mg/g dry weight), and water (6%) content, whereas mycelia consists of protein (42%), carbohydrate (42%), fat (6%), ash (4%), amino acids (30.6 mg/g dry weight), and water (4%) content. The fungal body also contains unsaturated fatty acids, saturated fatty acids, and other elements. Some potential bioactive compounds such as γ-aminobutyric acid (GABA), ergothioneine, and lovastatin were also found to be reported in H. erinaceus[15]. Thus, mushroom H. erinaceus has been used to develop several functional foods and used to improve quality of the foods. The mushrooms are consumed as the main dish in dining or as a supporting food. Currently, mushroom based fermented non-alcoholic beverages are trending in the Asian countries.
The probiotic bacteria mediated fermented mushroom beverages are effective functional foods. We have reported the production of l-glutamic acid (GA), and GABA rich fermented H. erinaceus juice using Lactobacillus brevis HP2 and Lactobacillus fermentum HP3 strains as a starter culture. Moreover, the factors (K2HPO4, pH, and temperature) influencing the production of GA and GABA was also reported [16]. Woraharn et al.[17] reported the development of l-glutamine and l-glutamic acid rich fermented H. erinaceus beverage using Enterococcus faecalis (G414/1) mediated fermentation. Probiotic mediated fermented H. erinaceus beverages are the best health promoting supplements with added probiotic benefits. Li et al.[18] described the use of H. erinaceus as a substrate for the production of vinegar and wine, and the product was found to be accepted by the human volunteers.
A dry powder of H. erinaceus mycelia has been used in preparing bread. Addition of 5% of H. erinaceus mycelia powder acted as additives in the preparation of bread, which also enhances the nutritional value of the bread. The presence of GABA and ergothioneine helps to improve the brain and heart functions [19], [20], [21].

4. Antihyperglycemic activities
Due to the high antioxidant potential and bioactive compounds, H. erinaceus has been used for the management of metabolic disorders, especially for diabetic treatments.
Wang et al.[22] demonstrated the anti-hyperglycemic property of methanol extract of H. erinaceus in streptozotocin induced diabetes Wistar rats. The supplementation of 20–100 mg of H. erinaceus extract per kg of body weight showed the reduction in blood glucose, serum triglyceride, and total cholesterol levels. The protective effect of methanol extract of H. erinaceus was found to be in a dose-dependent manner. About 100 mg of extract (per kg of body weight) supplementation showed a significant level of improvement in host health.
The hypoglycemic and antihyperlipidemic activities of aqueous extract of H. erinaceus have been reported using experimental rat model. The supplementation of H. erinaceus extract (100–200 mg/kg body weight) improved the serum insulin level and reduced the glucose level in streptozotocin induced diabetic rats. The researcher also reported that the supplementation of H. erinaceus aqueous extract exhibited antihyperlipidemic activities, and improved the free radical scavenging enzymes [23].
Yi et al.[24] reported that the ethanolic extract of H. erinaceus exhibited the anti-neuropathic pain activity in alloxan induced diabetic neuropathic Wistar rat model. About 40 mg of an ethanolic extract of H. erinaceus (per kg of body weight) supplementation reduced the neuropathic pain, increased the inhibition of lipid peroxidation and improved the activities of antioxidant enzymes such as lactate dehydrogenase, glutathione peroxidase, glutathione reductase, catalase, Na+K+ATPase, and glutathione S transferase in the experimental rats. The report claimed that the enhancement of antioxidant system of the host by H. erinaceus extract could be responsible for the amended diabetic neuropathy.
Wu and Xu [25] reported the in vitro antidiabetic nature of H. erinaceus and revealed that inhibition of α-glycosidase and aldose reductase activity was in a dose-dependent way. Xue et al.[26] explained the reduction of blood glucose, and improvement of sugar tolerance level in alloxan-induced diabetic mice supplemented with polysaccharides of H. erinaceus.
The fermented H. erinaceus juice supplementation enhanced the health of streptozotocin induced diabetic rats. The body mass and serum insulin level were increased, and the fasting plasma glucose was reduced in the diabetes rats of the supplemented group. The level of inflammatory markers was reduced, which confirms that the fermented H. erinaceus juice prevents the diabetes rat from inflammatory damages (Unpublished data) (Table 2).
Table 2. Reported antihyperglycemic activities of H. erinaceus.

S. No. Experimental model Supplementation Outcome Refs
1 Alloxan-induced diabetic mice Polysaccharides of H. erinaceus (6–25 mg/kg b.wt) Reduced blood glucose level.
Enhanced the sugar tolerance level. [26]
2 Streptozotocin induced diabetes Wistar rat Methanol extract of H. erinaceus (20–100 mg/kg b.wt) Reduced blood glucose, serum triglyceride and total cholesterol levels. [22]
3 Streptozotocin mediated diabetes induced Wistar rat Aqueous extract of H. erinaceus (100–200 mg/kg b.wt) Reduced serum glucose level.
Improved serum insulin level.
Improved antioxidant enzyme activities.
Reduced lipid related disorders. [23]
4 Alloxan induced diabetic neuropathic Wistar rat model Ethanol extracts of H. erinaceus (40 mg/kg b.wt) Reduced serum and urine glucose level.
Improved the enzyme activities (lactate dehydrogenase, glutathione peroxidase, glutathione reductase, catalase, Na+K+ATPase, and glutathione S transferase) and inhibition of lipid peroxidation.
Attenuation of diabetic neuropathy. [24]
5 Streptozotocin induced diabetes Wistar rat. Probiotic mediated fermented H. erinaceus Juice Reduced blood sugar level, slightly increased the serum insulin level.
Improved the health status of experimental rat Unpublished data

5. Other health benefits
Apart from antihyperglycemic activity, H. erinaceus has been reported for exhibiting several health benefits. For example, agglutinin of H. erinaceus exhibited antiproliferative activity against hepatoma, and HIV-1 reverse transcriptase inhibitory activity [27]. The polysaccharides of H. erinaceus could regulate the pro-inflammatory cytokines, induce the macrophage mediated immune response, and induce the dendritic cells maturation [28], [29]. H. erinaceus nullifies the gastric mucosal injury, and gastric ulcer [30]. The free radical scavenging, hepatoprotective, neuroprotective, neurodegenerative, hypolipidemic, anti-fatigue, and anti-aging activities of H. erinaceus polysaccharides have also been reported [31], [32], [33], [34], [35], [36]. H. erinaceus polysaccharides were found to be active against Helicobacter pylori[37].

6. Conclusions
The mushroom H. erinaceus is composed of many bioactive compounds with proven health promoting properties. Several patents were filed for the pharmacological applications and formulations made using the bioactive compounds of H. erinaceus, especially polysaccharides [38]. Still, a gap remains in transferring the information to the needy people. H. erinaceus is an affordable natural, healthy food. The improvement of existing foods and development of new H. erinaceus based functional foods are necessary to explore the medicinal property of the mushroom for the betterment of human life, primarily to treat and manage the diabetic condition. Further, scientific information is required concerning the influence of H. erinaceus supplementation on the hyperglycemic status of humans, the prescribed dose for the management of the diabetic condition, and affordable form of supplementation (like fermented H. erinaceus juice, or H. erinaceus extract, etc.), which help to advance the alternative medications for diabetes.

Conflict of interest statement
All authors declare that they have no conflict of interest.
Acknowledgments
The authors gratefully acknowledge the Faculty of Pharmacy and Chiang Mai University, Chiang Mai, Thailand. BSS wish to acknowledge the CMU Post-Doctoral Fellowship [Ref: No. 6592(11)/01501, dated 24 February 2017], Chiang Mai University, Chiang Mai, Thailand.
 

[invalidusername]

"Anxiety and Depressive symptoms have also been reduced in humans fed 2g of Yamabushitake, via cookies"

 

Why can't all medication follow suit!!

 

Thanks for this Hat - just to say the cabdirect link requires login, so anyone looking for the text for this on the depression/anxiety can download directly from the link below;

 

https://bisforbanana...ceus-intake.pdf

 

....also good for frustration and palpatations.

[fishinghat]

Thanks for the note IUN.

 

The one table I reference on the amino acid content is very interesting, especially the GABA and Glutamate concentrations.

[invalidusername]

So this shows the difference between the dry substance and fermented juice properties?

[fishinghat]

Yrs, and they are very different.