Enokitake

Flammulina velutipes


(from Medicinal Mushrooms – A Clinical Guide by Martin Powell)

Japanese name – Enokitake
Chinese name – Jin Zhen Gu / Dong Gu
English name – Velvet Foot/Winter Mushroom/Golden Needle Mushroom

A common culinary mushroom, F. velutipes was the second earliest mushroom to be cultivated artificially (cultivation started around 800 AD, following Auricularia auricula ~600 AD, and before Lentinus edodes ~1000 AD).

It shows considerable clinical promise, especially for cancer prevention protocols.

A study of 174,505 inhabitants of the Nagano area of Japan compared the cancer death rates among F. velutipes farmers with rates in the general population over a 15 year period (1972-86) and found that the F. velutipes farmers had a much lower death rate of 97.1 per 100,000, instead of 160.1 per 100,000 in the general population, with the suggestion that this was due to increased consumption of F. velutipes1.

Following on from the above study a case-control study was conducted to investigate the relationship between risk reduction of stomach cancer and intake of edible mushrooms in the same prefecture from 1998 to 2002. While the odds ratio (OR) of subjects who were eating hardly any mushrooms or mushrooms less than once a week was 1.00, consumption of F. velutipes more than three times a week produced a reduction to 0.66 (the OR of those taking Lentinus edodes (Shiitake) more than three times a week was 0.95)2.

As well as immunomodulatory polysaccharides3,4, F. velutipes is notable for its high protein content (31.2%) and large number of protein rich components with strong immuno-modulatory and anti-cancer activity5-9.

F. velutipes extracts also demonstrate strong tyrosinase inhibition10.

CancerF. velutipes extracts show exceptionally high anti-cancer activity in vitro. In one study of extracts from 38 mushrooms carried out by Bastyr University, F. velutipes had the highest level of inhibitory activity against two oestrogen dependent and one independent breast cancer cell lines11. In a separate study of aqueous extracts from 20 mushrooms and 3 mushroom polysaccharides, the aqueous extract from F. velutipes, together with that from Pleurotus ostreatus showed the highest level of cytotoxic activity against androgen-independent prostate cancer cells12.

In vivo, EA6, a protein bound polysaccharide isolated from the fruiting body of F. velutipes augmented humoral immunity, cellular immunity, and IL-2 production in mice bearing Meth-A fibrosarcoma at 10mg/kg and administration after surgery remarkably inhibited growth of the rechallenged Meth-A solid tumor, while Proflammin (90% protein, 10% polysaccharide) isolated from the mycellium of F.velutipes abolished suppression of immunocompetence after cryosurgery at 10mg/kg/day13.

Another protein from F. velutipes, Fve, protected mice against liver cancer through activation of both innate and adaptive immune responses when administered orally at a dose of 10mg/kg14.

In clinical studies EEM, a combination of extracts from F. velutipes and Hypsizygus marmoreus, revealed superior results to MPA (methylacetoxyprogestrone) on the cachexia of advanced cancer patients with better clinical response, performance status (PS), and quality of life (QOL). EEM supplementation in combination with anticancer drugs improved the clinical response rate, PS, and QOL of advanced cancer patients compared to patients treated with anticancer drugs alone. EEM supplementation also reduced precancerous lesions on the oesophageal mucosa2.

Anti-viral – Co-administration of Fve, a protein from F.velutipes, with immunization against HPV-16 led to 60% of mice remaining tumor-free 167 days after challenge with tumor cells compared to 20% of those receiving immunization alone. The co-immunized mice showed enhanced production of HPV-16 E7 oncoprotein-specific antibodies as well as expansion of HPV-16 E7-specific interferon (IFN)-gamma-producing CD4(+) and CD8(+) T cells compared to mice immunized with HPV-16 E7 alone15.

Proteins from F. velutipes also show direct anti-viral activity, including ribosome inactivating activity and inhibition of human immunodeficiency virus (HIV-1) reverse transcriptase, beta-glucosidase and beta-glucuronidase16.

Food Allergies – Mice orally given five daily 200 μg doses of protein from F. velutipes before and after each of two intraperitoneal injections of ovalbumin significantly reduced symptoms of anaphylaxis and levels of plasma histamine on subsequent oral challenge with ovalbumin and demonstrated an impaired OVA-specific IgE response with a Th1-predominant cytokine profile17. Other research has demonstrated the ability of the F. velutipes protein Fve to enhance eosinophil apoptosis, with therapeutic implications for eosinophil-related allergic inflammation, and of an ethanol extract to suppress hypersensitive immune response 18-20.

CLINICAL SUMMARY
Main Therapeutic Application – Dietary supplementation in patients at risk of cancer
Key Component – Proteins and polysaccharides
Dose – 3-5g dried fruiting body equates to 30-50g fresh mushroom and provides cost effective long term supplementation

1. Beneficial effects of edible and medicinal mushrooms on health care. Ikekawa T – Int J Med Mushr. 2001;3(4):8-12
2. Cancer Risk Reduction by Intake of Mushrooms and Clinical Studies on EEM. Ikekawa T. Int J Med Mush. 2005;7(3):347
3. Inhibitory activity of polysaccharide extracts from three kinds of edible fungi on proliferation of human hepatoma SMMC-7721 cell and mouse implanted S180 tumor. Jiang S.M, Xiao Z.M, Xu Z.H. World J Gastroenterol. 1999;5(5):404-407.
4. Investigation of immunomodulating activity of the medicinal mushroom Flammulina velutipes (Curt.: Fr.) P. Karst. in vitro. Cytokine induction by fruiting body extract Badalyan S, Hambardzumyan L.A. Int J Med Mush. 2001;3(2-3):110-111
5. Effect of Flammulina velutipes polysaccharides on production of cytokines by murine immunocytes and serum levels of cytokines in tumor-bearing mice. Chang H.L, Lei L.S, Yu C.L, Zhu Z.G, Chen N.N, Wu S.G. Zhong Yao Cai. 2009;32(4):561-3.
6. FIP-fve stimulates interferon-gamma production via modulation of calcium release and PKC-alpha activation. Ou C.C, Hsiao Y.M, Wu W.J, Tasy G.J, Ko J.L, Lin M.Y. J Agric Food Chem. 2009;57(22):11008-13.
7. Fungal immunomodulatory protein from Flammulina velutipes induces interferon-gamma production through p38 mitogen-activated protein kinase signaling pathway. Wang P.H, Hsu C.I, Tang S.C, Huang Y.L, Lin J.Y, Ko J.L. J Agric Food Chem. 2004;52(9):2721-5.

8. Flammulin: a novel ribosome-inactivating protein from fruiting bodies of the winter mushroom Flammulina velutipes. Wang H.X, Ng T.B. Biochem Cell Biol. 2000;78(6):699-702.

9. High processing tolerances of immunomodulatory proteins in Enoki and Reishi mushrooms. Tong M.H, Chien P.J, Chang H.H, Tsai M.J, Sheu F. J Agric Food Chem. 2008;56(9):3160-6.

10. Isolation of 1′,3′-dilinolenoyl’-2′-linoleoylglycerol with tyrosinase inhibitory activity from Flammulina velutipes. Jang S.G, Jeon K.S, Lee E.H, Kong W.S, Cho J.Y. J Microbiol Biotechnol. 2009;19(7):681-4.

11. In vitro effects on proliferation, apoptosis and colony inhibition in E-dependent and ER-independent human breast cancer cells by selected mushroom species. Gu Y.H, Leonard J. Oncology Reports. 2006;15:417-423

12. Cytotoxic effect of oyster mushroom Pleurotus ostreatus on human Androgen-independent prostate cancer PC-3 Cells. Gu Y.H, Sivam G. J Med Food. 2006;9(2):196-204

13. Immunomodulation and antitumor activity of a mushroom product, Proflamin, isolated from Flammulina velutipes (W. Curt.: Fr.) Singer (Agaricomycetideae). Maruyama H, Ikekawa T. Int J Med Mushr. 2007;9(2):20.

14. Oral administration of an Enoki mushroom protein FVE activates innate and adaptive immunity and induces anti-tumor activity against murine hepatocellular carcinoma. Chang H.H, Hsieh K.Y, Yeh C.H, Tu Y.P, Sheu F. Int Immunopharmacol. 2010;10(2):239-46.

15. Coadministration of the fungal immunomodulatory protein FIP-Fve and a tumour-associated antigen enhanced antitumour immunity. Ding Y, Seow S.V, Huang C.H, Liew L.M, Lim Y.C, Kuo I.C, Chua K.Y. Immunology. 2009;128(1Sup):881-94.

16. Isolation and characterization of velutin, a novel low-molecular-weight ribosome-inactivating protein from winter mushroom (Flammulina velutipes) fruiting bodies. Wang H, Ng T.B. Life Sci. 2001;68(18):2151-8.

17. Oral administration of an edible-mushroom-derived protein inhibits the development of food-allergic reactions in mice. Hsieh K.Y, Hsu C, Lin J.Y, Tsai C.C, Lin R.H. Clin Exp Allergy. 2003;33(11):1595-602.
18. The modulatory effect of FIP-fve on eosinophil apoptosis in vitro indicates that it may have some therapeutic effect on eosinophil-related allergic inflammation in vivo. J Formos Med Assoc. 2007;106(1):36-43.
19. Eosinophil apoptosis induced by fungal immunomodulatory peptide-fve via reducing IL-5alpha receptor. Hsieh C.W, Lan J.L, Meng Q, Cheng Y.W, Huang H.M, Tsai J.J. J Formos Med Assoc. 2007;106(1):36-43.
20. Inhibitory effects of edible higher Basidiomycetes mushroom extracts on mouse type IV allergy. Sano M, Yoshino K, Matsuzawa T, Ikekawa T. Int J Med Mushr. 2002;4(1):37-41

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