Lion's Mane

Last Updated: September 28 2022

Lion's Mane, known as Yamabushitake, is a dietary mushroom that can be a supplement. It appears to be a promising cognitive enhancer and immunomodulator (thought to stimulate or suppress inflammation depending on context).

Lion's Mane is most often used for.



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1.

Sources and Composition

1.1

Sources

Lion's Mane is a mushroom that grows on old or dead broadleaf trees, and is consumed in Japan and China without reported harmful effects.[1]

Some common names for this mushroom also include Monkey's Head, Yamabushitake, and Satyr’s Beard[2] and is sometimes called Houtou as that is the name of a sports drink which contained Hericium erinaceus (11th Asia Sport Festival in China of 1990).[3][2]

1.2

Composition

The mushroom Lion's Mane (Hericium erinaceus) contains:

  • Hericenones A and C-H[4][5][6]
  • Erinacines A-K[7][8]
  • Orcinol derivatives (Mycelium)[9]
  • Sialic-acid binding lectin[10]
  • Sterols, such as ergosterol and beta-sitosterol.[11]

And a polysacchaide component (Hericium erinaceus )

  • Polysaccharides, named HEF-P and belonging to the beta-glucan family; which can be broken down into four polysaccharides[12][13][14] The percentage of polysaccharides in the fruiting bodies seems to be around 20%, with 18.59% found with an ethanol extraction[14][15] with the overall structure of these polysaccharides comprising xylose (7.8%), ribose (2.7%), glucose (68.4%), arabinose (11.3%), galactose (2.5%) and mannose (5.2%).[16]

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Like most medicinal mushrooms, Lion's Mane appears to have bioactive polysaccharides (carbohydrates) in addition to some ethanolic soluble molecules

The total phenolic content of Lion's Mane appears to be in the range of 10.20+/-2.25mg gallic acid equivalents (GAE) per gram (about 1%)[17] with the hot water extract, which appears to be up to 5-fold higher than oven cooked levels and either methanolic or freeze-dried fruit bodies.[18] This 10.20+/-2.25mg GAE/g (phenolic content) is significantly less than the reference drug of Quercetin (194.24+/-7.58) and on a potency basis the overall antioxidant potential of lion's mane is about 17.7% that of quercetin in vitro.[17]

The polysaccharides themselve are also active in vivo, with 300mg/kg of the polysaccharides daily for 15 days can reduce the oxidative changes induced by ischemia/reperfusion.[16]

The phenolic antioxidant potential of Lion's Mane is significantly less than the reference drugs of Quercetin and gallic acid, although the polysaccharide content does also appear to be bioactive

2.

Interactions with Neurology

2.1

Neurogenesis

Lion's Mane has been noted to increase mRNA expression of nerve-growth factor (NGF) 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.[1] When testing hericenones C-E, none were found effective in the range of 10-100ug/mL[1] and inhibiting JNK signalling appears to prevent lion's mane from acting (with p38 MAPK, PKA, PKC, and MEK not being involved).

An increase in NGF mRNA has been detected in the hippocampus, but not cortex, of mice given 5% of the diet as lion's mane for a period of seven days to around 1.3-fold of control.[1]

Lion's Mane ethanolic extract appears to increase NGF mRNA levels, and this has been confirmed following oral administration to mice

Secretion of NGF from astrocytes has been noted to be increased with 150ug/mL of the ethanolic extract but not 50-100ug/mL[1] while 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.[19]

Seceretion of NGF from astrocytes has been noted to be increased with incubation of lion's mane ethanolic extract

When looking at neurons specifically, lion's mane appears to promote neuronal prolongation and formation of myelin[20]

2.2

Glutaminergic Neurotransmission

Neuronal excitability from glutamic acid appears to be attenuated in the presence of lion's mane extracts,[20]

2.3

Neuroprotection

An analogue of the Hericenones, called 3-hydroxyhericenone, has been implicated in preserving neurons from death induced by endoplasmic reticulum stress.[6] This mechanism of action is also seen with various benzene compounds in lion's mane.[21]

It has also been shown, in vitro, to enhance myelination (production of myelin sheath) of neurons, which may be downstream of NGF.[22]

2.4

Cognition

Lion's Mane appears to protect rats against cognitive decline caused by β-amyloid pigmentation at the same 5% of the diet seen previously.[23]

One human study using 3g of 98% lion's mane powder (in capsule form) showed significantly improvements on a rating scale of dementia in persons suffering from general cognitive decline.[24] The supplement increased cognition 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.[24]

Anxiety and Depressive symptoms have also been reduced in humans fed 2g of lion's mane, via cookies, over the course of 4 weeks.[25] There was a significant difference between groups on the measurements of concentration and irritability, favoring the lion's mane group.[25]

2.5

Nerve Injury

In one study conducted in rats, lion's mane water extract was able to promote neuronal regrowth after crushing injury. Rats that had a gluteal nerve damaged (purposefully) during surgery were able to walk better after ingestion of water containing the extract of the fruits.[26] Two doses used in this study were 10 or 20mL per kg bodyweight daily, but the exact mg or mmol dose was not recorded; the two doses, however, did not differ between each other.[26] This was conducted as a follow-up to an in vitro study suggesting neuronal growth from lion's mane, which showed no toxic symptoms.[27]

3.

Cardiovascular Health

3.1

Blood Pressure

Hericenone B has been shown to exert anti-platelet actions by inhibiting signalling from collagen through α2/β1 to release arachidonic acid (one of the two receptors that mediates thrombosis via collagen[28]); the mechanism appears to be potent but specific in tested rabbits, with complete inhibition at 30μM (similar to 5μM aspirin as reference drug) and near complete at 10μM.[29] Interestingly, hericenones C-E failed to have any influence on collagen-induced platelet aggregation, and while hericenone B was active on other forms of aggregation (adrenaline and U46619 but not ADP nor thrombin) it was less effective.[29]

Hericenone B appears to potently and specifically inhibit collagen-induced platelet aggregation, with other hericenones not having much of an effect and other forms of aggregation not being significantly affected. The concentration this occurs at suggests that it is biologically relevant

Lion's Mane appears to be an ACE inhibitor (hot water extract of the fruiting bodies) with an IC50 value of 580+/-23µg/mL, significantly less than the most potent tested mushroom Ganoderma lucidum (50µg/mL).[17]

Hot water extracts of mushrooms tends to be more potent ACE inhibitors than ethanolic or methanolic extracts,[30][31] and mushroom bioactives that have been noted to inhibit ACE include D-mannose (IC50 of 3mg/mL)[32] and L-pipecolic acid (IC50 of 23.7mg/mL).[33] As these molecules themselves are weaker than Lion's Mane, it is currently thought that bioactives peptides underlie the ACE inhibitor potential as they have been detected in mushrooms before (Val-Ile-Glu-Lys-Tyr-Pro[34] and Gly-Glu-Pro[31])

Lion's mane has ACE inhibiting properties, although they appear to be pretty weak and may not be biologically relevant. The exact molecule underlying these effects is not currently known, but it may be a bioactive peptide

3.2

Lipids and Cholesterol

Both a hot water and ethanolic extract of lion's mane 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.[35] These hypolipidemic effects were also observed in liver tissue (29.8% hot water and 38.8% ethanolic) and was thought to be related to the ability of the ethanolic extract to act as a PPARα agonist with an EC50 value of 40µg/mL; there was an increase in genes downstream of PPARα but no changes in PPARα expression.[35]

Lion's Mane 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,[35] an extract derived from the mycelium of lion's mane (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.[36]

Although the fruiting body of the mushroom (edible portion) does not appear to significantly influence lipoprotein and cholesterol metabolism, the mycelium may reduce cholesterol

4.

Fat Mass and Obesity

4.1

Mechanisms

Supplementation of both the hot water and ethanolic extracts of lion's mane to mice (1.896-3.16g/kg hot water and 2.016-3.36g/kg ethanolic) has been found to increase the expression of several genes involved in fat metabolism including Acad1, Srebf1, and Slc27a1, which were thought to be due to activating PPARα.[35]

Lion's Mane appears to be a PPARα agonist, which may contribute to fat burning properties

4.2

Interventions

Supplementation of lion's mane (1.896-3.16g/kg hot water extract or 2.016-3.36g/kg of the ethanolic extract) to mice is able to attenuate weight gain during a high fat diet by 30% (hot water) and 42.4% (ethanolic) associated with less fat accumulation in the liver and mesenteric adipose tissue.[35]

The mycelium extract at 50-200mg/kg in rats, despite having cholesterol reducing properties, has failed to significantly influence body weight over the course of four weeks.[36]

5.

Inflammation and Immunology

5.1

Mechanisms

Lion's Mane has been noted to suppress LPS-induced macrophage activation (mostly chloroform fraction, but also seen with water and alcoholic extracts) associated with less activation of c-Jun N-terminal kinase and less nuclear translocation of NF-kB.[37]

The polysaccharide known as HEF-AP Fr II (a beta-glucan), conversely, has been found to stimulate macrophage activity itself as assessed by TNF-α and IL-β release at a concentration of 1mg/mL.[14] This may be related to the increase in macrophage and T-cell count seen with incubations of this mushroom.[38]

Differing compounds in Lion's Mane appear to differently modulate the immune system, with the polysaccharides appearing to be immunostimulatory but other molecules (mostly in the chloroform extract) appearing to suppress macrophage activation

5.2

Interventions

A study in topically wounded rats with the water extract of lion's mane has noted that immune cell accumulation in the wound was reduced in the lion's mane group relative to control.[39]

Some suppression of chemotaxis may occur in wounds

6.

Interactions with Cancer Metabolism

6.1

Colon

In vitro, the hot water and ethanolic extracts of lion's mane 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.[40]

Both the hot water and ethanolic extracts of lion's mane 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.[40]

7.

Interactions with Aesthetics

7.1

Skin

Lion's Mane is associated with increasing the rate of repair of flesh wounds when the water extract is applied to the wound.[39]

8.

Safety and Toxicity

Toxicology studies in rats suggest that doses up to 5g/kg bodyweight are safe in rats when given as MUNOPHIL, which is a combination of lion's mane and Panax Ginseng.[41] The percentage of this compound by weight that is lion's mane was not listed.

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 lion's mane daily for 4 months in dosages commonly bought.[42] The connection between the two, when rated, is seen as a 'probably' connection.[43]

References
1.^Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata NNerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human astrocytoma cellsBiol Pharm Bull.(2008 Sep)
4.^Yaoita Y, Danbara K, Kikuchi MTwo new aromatic compounds from Hericium erinaceum (BULL.: FR.) PERS(1)Chem Pharm Bull (Tokyo).(2005 Sep)
6.^Ueda K, Tsujimori M, Kodani S, Chiba A, Kubo M, Masuno K, Sekiya A, Nagai K, Kawagishi HAn endoplasmic reticulum (ER) stress-suppressive compound and its analogues from the mushroom Hericium erinaceumBioorg Med Chem.(2008 Nov 1)
11.^Li JL, Lu L, Dai CC, Chen K, Qiu JYA comparative study on sterols of ethanol extract and water extract from Hericium erinaceusZhongguo Zhong Yao Za Zhi.(2001 Dec)
16.^Han ZH, Ye JM, Wang GFEvaluation of in vivo antioxidant activity of Hericium erinaceus polysaccharidesInt J Biol Macromol.(2013 Jan)
17.^Abdullah N, Ismail SM, Aminudin N, Shuib AS, Lau BFEvaluation of Selected Culinary-Medicinal Mushrooms for Antioxidant and ACE Inhibitory ActivitiesEvid Based Complement Alternat Med.(2012)
21.^Ueda K, Kodani S, Kubo M, Masuno K, Sekiya A, Nagai K, Kawagishi HEndoplasmic reticulum (ER) stress-suppressive compounds from scrap cultivation beds of the mushroom Hericium erinaceumBiosci Biotechnol Biochem.(2009 Aug)
22.^Kolotushkina EV, Moldavan MG, Voronin KY, Skibo GGThe influence of Hericium erinaceus extract on myelination process in vitroFiziol Zh.(2003)
23.^Mori K, Obara Y, Moriya T, Inatomi S, Nakahata NEffects of Hericium erinaceus on amyloid β(25-35) peptide-induced learning and memory deficits in miceBiomed Res.(2011 Feb)
25.^Nagano M, Shimizu K, Kondo R, Hayashi C, Sato D, Kitagawa K, Ohnuki KReduction of depression and anxiety by 4 weeks Hericium erinaceus intakeBiomed Res.(2010 Aug)
26.^Wong KH, Naidu M, David P, Abdulla MA, Abdullah N, Kuppusamy UR, Sabaratnam VPeripheral Nerve Regeneration Following Crush Injury to Rat Peroneal Nerve by Aqueous Extract of Medicinal Mushroom Hericium erinaceus (Bull.: Fr) Pers. (Aphyllophoromycetideae)Evid Based Complement Alternat Med.(2011)
28.^Farndale RW, Sixma JJ, Barnes MJ, de Groot PGThe role of collagen in thrombosis and hemostasisJ Thromb Haemost.(2004 Apr)
29.^Mori K, Kikuchi H, Obara Y, Iwashita M, Azumi Y, Kinugasa S, Inatomi S, Oshima Y, Nakahata NInhibitory effect of hericenone B from Hericium erinaceus on collagen-induced platelet aggregationPhytomedicine.(2010 Dec 1)
32.^Hagiwara SY, Takahashi M, Shen Y, Kaihou S, Tomiyama T, Yazawa M, Tamai Y, Sin Y, Kazusaka A, Terazawa MA phytochemical in the edible Tamogi-take mushroom (Pleurotus cornucopiae), D-mannitol, inhibits ACE activity and lowers the blood pressure of spontaneously hypertensive ratsBiosci Biotechnol Biochem.(2005 Aug)
35.^Hiwatashi K, Kosaka Y, Suzuki N, Hata K, Mukaiyama T, Sakamoto K, Shirakawa H, Komai MYamabushitake mushroom (Hericium erinaceus) improved lipid metabolism in mice fed a high-fat dietBiosci Biotechnol Biochem.(2010)
37.^Kim YO, Lee SW, Oh CH, Rhee YHHericium erinaceus suppresses LPS-induced pro-inflammation gene activation in RAW264.7 macrophagesImmunopharmacol Immunotoxicol.(2011 Nov 29)
41.^Park ID, Yoo HS, Lee YW, Son CG, Kwon M, Sung HJ, Cho CKToxicological study on MUNOPHIL, water extract of Panax ginseng and Hericium erinaceum in ratsJ Acupunct Meridian Stud.(2008 Dec)
42.^Nakatsugawa M, Takahashi H, Takezawa C, Nakajima K, Harada K, Sugawara Y, Kobayashi S, Kondo T, Abe SHericium erinaceum (yamabushitake) extract-induced acute respiratory distress syndrome monitored by serum surfactant proteinsIntern Med.(2003 Dec)