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Hericium erinaceus, NGF e SM

Le Hericium erinaceus: des propriétés essentiellement dépendantes du neuronal
growth factor

B. Donatini
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Le Hericium erinaceus (HE) induit la synthèse de neuronal growth factor (NGF), impliqué dans les maladies
neurodégénératives comme la maladie d’Alzheimer ou plus généralement dans les troubles trophiques
(estomac, intestin, foie) ou les cicatrisations (peau, cartilage, os). Le HE stimule aussi les voies TH1 et TH2
(antiparasitaire puissant), ce qui le positionne parmi les aliments potentiellement utiles contre les maladies
auto-immunes IL17-dépendantes. L’effet du NGF dépend de la vitamine D.
Hericium erinaceus induces the synthesis of neuronal growth factor (NGF), implicated in neuro-degenerative
diseases such as Alzheimer dementia or more generally in atrophic diseases (stomac, intestinal mucosa, liver) or
fibroblasts, chondrocytes or osteoblasts stimulation. HE also stimulates immunity, especially TH1 and TH2
pathways which enables this mycelia to be considered as a good candidate in auto-immune diseases therapy.
The efficacy of NGF relies on an adequate titration of vitamin D.
Hericium erinaceus
(from Medicinal Mushrooms – A Clinical Guide by Martin Powell)
Japanese Name – Yamabushitake
Chinese Name – Hou Tou Gu (Monkey Head Mushroom)
English Name – Lion’s Mane Mushroom / Hedgehog Mushroom
This delicious mushroom has been referred to as ‘Nature’s Nutrient for the Neurons’ on account of its ability to
stimulate the production of nerve growth factor (NGF)1,2.
NGF plays an essential role in the differentiation and survival of several nerve cell populations in the central
and peripheral nervous system and lower than normal levels of NGF have been shown to be linked to early
stages of both alzheimers disease and dementia3-8.
Although therapeutic interest has largely focusssed on its importance for neurological function, NGF has a
much wider role in maintaining homoeostasis in the body9,10. It is known to have insulinotropic, angiogenic,
and antioxidant properties and reduced plasma levels of NGF have been associated with cardiovascular
diseases and metabolic syndromes, including type 2 diabetes11,12. It has been shown to accelerate wound
healing and there is also evidence that it could be useful in the treatment of skin and corneal ulcers13. Animal
studies have shown NGF to have a profound effect on airway inflammation and asthma-related symptoms with
increased NGF levels observed in bronchoalveolar lavage fluid and serum from patients with asthma14.
NGF also has a dynamic relationship with the immune system. Production of NGF is increased after brain
injury, in part due to cytokines produced by immune cells. At the same time cells of the immune system express
receptors for NGF, which is involved in immune modulation15.
Two families of cyathane derivatives from H. erinaceus have been identified as being active in the stimulation
of NGF production: the hericenones (isolated from the fruiting body) and the erinacines (isolated from the
mycelium). Critically these molecules are small enough to pass through the blood-brain barrier. There is also
evidence that they can increase myelination1,16,17.
In China the mycelium is used to make Hericium erinaceus Pills to treat gastric and duodenal ulcers, chronic
gastritis, gastric and oesophageal cancer.
Dementia – In controlled studies H. erinaceus supplementation showed beneficial effects in patients with mild
dementia. In one study 6 out of 7 patients showed improvement in functional capacity (understanding,
communication, memory etc.) while all 7 showed improved Functional Independence Scores (eating, dressing,
walking etc.), after consuming 5g H. erinaceus fruiting body daily in soup1. In another study, 30 patients aged
50-80 with mild dementia were randomised into treatment and control groups. H. erinaceus was given as
tablets at 3g/day for 16 weeks and produced significant increases in cognitive function in the treatment group.
However, four weeks after the conclusion of the trial, cognitive function scores decreased17.
MS – H. erinaceus fruiting body extract has been shown to improve the myelination process in mature
myelinating fibers with possible benefits for MS patients18,19. NGF has also been shown to have a protective
effect on axons and myelin by suppressing the immune-mediated inflammatory processes responsible for
chronic brain destruction in neurodegenerative disorders such as MS by switching the immune response to an
anti-inflammatory, suppressive mode in a brain-specific environment13.
Neuropathy – NGF plays a role in pain sensitivity and low NGF levels have been linked to sensory neuropathy
in both in vivo and in vitro studies10. Enhanced NGF production has been shown to protect sensory function in
diabetic rats and NGF reduction has been shown to cause cardiac sensory neuropathy21,22.
Clinical studies with recombinant human nerve growth factor indicate benefit in patients with diabetic
polyneuropathy23 and NGF has also been reported to reduce pain in patients with HIV associated sensory
neuropathy24,25. However, ability to promote regeneration of sensory neurons has yet to be
Nerve Damage – Rats given aqueous extract of H. erinaceus fruiting bodies showed faster recovery from nerve
injury, suggesting potential for application of H. erinaceus in the early stages of nerve regeneration28.
MRSA – Extracts of both fruiting body and mycellium exhibit anti-MRSA activity with erinacines identified as
active compounds. In clinical tests in Japan MRSA is reported to have disappeared in a percentage of patients
whose diet was supplemented with H.erinaceus29.
GASTRITIS – One of the traditional indications for H. erinaceus, it appears likely that its beneficial effects in
this regard are also a function of the antibacterial action of its cyathane derivatives, with Helicobacter pylori
now known to be a major cause of chronic gastritis30-32.
Main Therapeutic Application – Dementia, Alzheimers and Nerve Damage. May have benefit for MS but
clinical evidence lacking.
Key Component – Cyathane derivatives including hericenones and erinacines
Dose – Clinical trials support the use of dried fruiting body at a dose of 3-5g/day for increasing NGF production
while animal studies on the use of H. erinaceus for gastric ulcers produced the best results with a daily intake of
500mg/kg, which equates to the dosage prescribed in the Chinese Phamacopoeia of 25-50g/day32,33. It is likely
that similar doses would be required in cases of MRSA.
High in-vitro NGF promoting activity of mycellial extracts and the fermentation broth also indicates potential
use of biomass products in this regard34,35.
Caution – Asthma and other allergic conditions. Erinacine E is a potent agonist of the Kappa opioid receptor
with potential hallucinogenic properties36.
1. The anti-Dementia effect of Lion’s Mane mushroom and its clinical application. Kawagishi H, Zhuang C,
Shnidman E. Townsend Letter for Doctors and Patients, 2004
2. Kawagishi H, Shimada A, Hosokawa S, Mori H, Sakamoto H, Ishiguro Y, Sakemi S, Bordner J, Kojima N,
Furukawa S. Erinacines E, F, and G, stimulators of nerve growth factor (NGF)-synthesis, from the mycelia of
Hericium erinaceum. Tetra Lett. 1996 37(41):7399-402.
3. Erinacine A increases catecholamine and nerve growth factor content in the central nervous system of rats.
Nutrition Research. ;25(6):617-623M. Shimbo, H. Kawagishi, H. Yokogoshi
4. NGF and BDNF: from nerves to adipose tissue, from neurokines to metabokines. Chaldakov G.N, Tonchev
A.B, Aloe L. Riv Psichiatr. 2009;44(2):79-87.
5. Development of a non invasive NGF-based therapy for Alzheimer’s disease. Covaceuszach S, Capsoni S,
Ugolini G, Spirito F, Vignone D, Cattaneo A. Curr Alzheimer Res. 2009;6(2):158-70.
6. Neurotrophins: from pathophysiology to treatment in Alzheimer’s disease. Schulte-Herbrüggen O, Jockers-
Scherübl M.C, Hellweg R. Curr Alzheimer Res. 2008;5(1):38-44.
7. One hundred years after the discovery of Alzheimer’s disease. A turning point for therapy? Giacobini E,
Becker R.E. J Alzheimers Dis. 2007;12(1):37-52.
8. Neurotrophic factors–a tool for therapeutic strategies in neurological, neuropsychiatric and
neuroimmunological diseases? Schulte-Herbrüggen O, Braun A, Rochlitzer S, Jockers-Scherübl M.C, Hellweg
R. Curr Med Chem. 2007;14(22):2318-29. Review.
9. Levi-Montalcini R (2004). “The nerve growth factor and the neuroscience chess board”. Prog. Brain Res.
146: 525–7.
10. Neurotrophin presence in human coronary atherosclerosis and metabolic syndrome: a role for NGF and
BDNF in cardiovascular disease?. Prog Brain Res. Chaldakov G.N, Fiore M, Stankulov I.S, Manni L, Hristova
M.G, Antonelli A, Ghenev PI, Aloe L. 2004;146:279–89.
11. Reduced plasma levels of NGF and BDNF in patients with acute coronary syndromes. Int J Cardiol. Manni
L, Nikolova V, Vyagova D, Chaldakov G.N, Aloe L. 2005;102(1):169–71.
12. Homo obesus: a metabotrophin-deficient species. Pharmacology and nutrition insight. Curr Pharm Des.
Chaldakov G.N, Fiore M, Tonchev A.B, Dimitrov D, Pancheva R, Rancic G, Aloe L. 2007;13(21):2176–9.
13. Nerve growth factor and wound healing. Prog Brain Res. Kawamoto K, Matsuda H. 2004;146:369–84
14. Expression of nerve growth factor in the airways and its possible role in asthma. Freund V, Frossard N.
Prog Brain Res. 2004;146:335–46.
15. Role of nerve growth factor and other trophic factors in brain inflammation”. Villoslada P, Genain C.P.
Prog Brain Res. 2004;146:403–14.
16. Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human astrocytoma cells. Mori K,
Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Biol Pharm Bull. 2008;31(9):1727-32.
17. Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a
double-blind placebo-controlled clinical trial. Mori K, Inatomi S, Ouchi K, Azumi Y, Tuchida T. Phytother
Res. 2009;23(3):367-72.
18. The influence of Hericium erinaceus extract on myelination process in vitro. Kolotushkina E.V, Moldavan
M.G, Voronin K.Y, Skibo G.G. Fiziol Z.H. 2003;49(1):38-45.
19. Hericium erinaceus (Bull.: Fr.) Pers. extract effect on nerve cells. Grygansky A.P, Moldavan M.G,
Kolotushkina O.V, Skibo G.G. Int J Med Mushr. 2001;3(2-3):152
20. Haploinsufficiency of the nerve growth factor beta gene in a 1p13 deleted female child with an insensitivity
to pain. Fitzgibbon G.J, Kingston H, Needham M, Gaunt L. Dev Med Child Neurol. 2009;51(10):833-7.
21. Protection of sensory function in diabetic rats by Neotrofin. Calcutt N.A, Freshwater J.D, Hauptmann N,
Taylor E.M, Mizisin A.P. Eur J Pharmacol. 2006;534(1-3):187-93.
22. Nerve growth factor is critical for cardiac sensory innervation and rescues neuropathy in diabetic hearts.
Ieda M, Kanazawa H, Ieda Y, Kimura K, Matsumura K, Tomita Y, Yagi T, Onizuka T, Shimoji K, Ogawa S,
Makino S, Sano M, Fukuda K. Circulation. 2006 ;114(22):2351-63.
23. Recombinant human nerve growth factor in the treatment of diabetic polyneuropathy. S. C. Apfel et al.
Neurology. 1998;51:695-702
24. Long-term treatment with recombinant nerve growth factor for HIV-associated sensory neuropathy. G.
Schifitto et al. Neurology. 2001;57:1313-1316
25. A phase II trial of nerve growth factor for sensory neuropathy associated with HIV infection. J. C.
McArthur et al. Neurology. 2000;54:1080-1088
26. Regeneration of primary sensory neurons. Donnerer J. Pharmacology. 2003;67(4):169-81.
27. Nerve growth factor and diabetic neuropathy. Pittenger G, Vinik A. Exp Diabesity Res. 2003;4(4):271-85.
28. Functional recovery enhancement following injury to rodent peroneal nerve by Lion’s Mane mushroom,
Hericium erinaceus (Bull.: Fr.) Pers. (Aphyllophoromycetideae). Wong K.H, Naidu M, David R.P, Abdulla
M.A, Abdullah N, Kuppusamy U.R, Sabaratnam V. Int J Med Mushr. ;11(3):20
29. Anti-MRSA compounds of Hericium erinaceous. Kawagishi H et al. Int J Med Mushr. 2005;7(3):350
30. A double-blind study of effectiveness of hericium erinaceus pers therapy on chronic atrophic gastritis. A
preliminary report. Xu C.P, Liu W.W, Liu F.X, Chen S.S, Liao F.Q, Xu Z, Jiang L.G, Wang C.A, Lu X.H. Chin
Med J (Engl). 1985;98(6):455-6.
31. Cytoprotective effects of Hericium erinaceus on gastric mucosa in rats. Yu C.G, Xu Z.M, Zhu Q.K et al.
Chinese J Gastrent. 1999-02
32. Effect of culinary-medicinal Lion’s Mane mushroom, Hericium erinaceus (Bull.: Fr.) Pers.
(Aphyllophoromycetideae), on Ethanol-induced gastric ulcers in rats. Abdulla M.A, Noor S, Sabaratnam V,
Abdullah N, Wong K.H, Ali H.M. Int J Med Mush. 2008;10(4):325-330
33. Chinese Pharmacopoeia, 2010. Beijing:Chinese Medicine Science and Technology Publishing House
34. Activity of aqueous extracts of Lion’s Mane mushroom Hericium erinaceus (Bull.: Fr.) Pers.
(Aphyllophoromycetideae) on the neural cell line NG108-15. Wong K.H, Vikineswary S, Abdullah N, Naidu M,
Keynes R. Int J Med Mushr. 2007;9(1):57-65
35. Neurotropic and trophic action of Lion’s Mane mushroom Hericium erinaceus (Bull.: Fr.) Pers.
(Aphyllophoromycetideae) extracts on nerve cells in vitro. Moldavan M.G, Grygansky A.P, Kolotushkina O.V,
Kirchhoff B, Skibo G.G, Pedarzani P. Int J Med Mush. 2007;9(1):
36. Erinacine E as a kappa opioid receptor agonist and its new analogs from a basidiomycete, Hericium
ramosum. Saito T, Aoki F, Hirai H, Inagaki T, Matsunaga Y, Sakakibara T, Sakemi S, Suzuki Y, Watanabe S,
Suga O, Sujaku T, Smogowicz AA, Truesdell SJ, Wong JW, Nagahisa A, Kojima Y, Kojima N. J Antibiot
(Tokyo). 1998 Nov;51(11):983-90.
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