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Inonotus obliquus

 (from Medicinal Mushrooms - A Clinical Guide by Martin Powell, Pub. Mycology Press 2014)

Japanese name - Kabanoanatake
Chinese name - Bai Hua Rong / Hua Jie Kong Jun
English name - Chaga

I. obliquus grows widely in the forests of Eastern Europe and Russia on several trees, including birch, alder and spruce, where it appears as a sterile growth or conk on the trunk of the tree. The fruiting body is reported to be found growing nearby but is extremely rare in nature.

Traditionally only I. obliquus growing on birch trees was used as a tea in the treatment of cancers including inoperable breast cancer, hip, gastric, parotid, pulmonary, stomach, skin, rectal and Hodgkin lymphoma and I. obliquus is recorded as a miraculous cure for cancer in Solzhenitsyn’s semi-autobiographical 1967 novel, ‘Cancer Ward’1.


The wisdom of using birch grown I. obliquus is supported by the finding that some of its key components are the triterpenoids betulin and betulinic acid, which occur naturally in a number of plants but primarily in the bark of the white birch (Betula pubescens - seen as the tree of life and fertility in many Eastern European and Siberian myths) from which it gets its name. Although it has been assumed that I. obliquus derives betulinic acid exclusively from the bark of host birch trees a recent study reported a small amount of betulin (0.12%) in I. obliquus mycelial biomass grown on rice indicating that some may also be
generated by the mushroom itself2.

Betulinic acid has been shown to induce mitochondrial apoptosis in different cancer cell lines and inhibit the enzyme topoisomerase3, which is essential for the unwinding and winding of the DNA strands in cell replication. In addition it possesses anti-retroviral, antiparasitic and anti-inflammatory properties4. It is currently being developed as an anti-cancer agent through the Rapid Access to Intervention Development program of the US National Cancer Institute and is also a major contributor to the anti-cancer action of mistletoe5.

Other important components of I. obliquus include polysaccharides and sterols. Its high phenolic content gives it exceptional antioxidant properties and a melanin complex has also been identified as having significant antioxidant and genoprotective properties6-8.


CANCER -Widely used in Poland and Russia as a folk remedy against cancer9, I. obliquus is now attracting increasing interest among practitioners with its combination of immune supporting polysaccharides and triterpenoid components with direct anti-cancer activity, especially betulinic acid derivatives10-14.

In vitro studies on betulinic acid have shown it to be highly effective against a wide variety of cancer cells: human melanoma, neuroectodermal (neuroblastoma, medulloblastoma, Ewing’s sarcoma) and malignant brain tumours, ovarian cancer, human leukaemia HL-60 cells and malignant head and neck squamous cell cancers, including those derived from therapy-resistant and refractory tumours15,17. However, it was found to have no effect on epithelial tumours, such as breast cancer, colon cancer, small cell lung cancer and renal cell cancer as well as T-cell leukaemia cells. Its anti-tumour activity has been related to its direct effects on mitochondria and induction of apoptosis, irrespective of cells p53 status18.

Both betulinic acid and polysaccharides from I.obliquus have significant in vitro activity against brain cancer cells with one study showing that betulinic acid exerted cytotoxic activity against primary tumour cells cultured from patients in 4 of 4 medulloblastomatumour samples tested and in 20 of 24 glioblastoma-tumour samples19, 20. It also shows great promise in combination with radiotherapy, exhibiting a strictly additive mode of growth inhibition in combination with radiation in human melanoma cells in one study and acting as a radiosensitizer in head and neck squamous cell cancers in another 21,22.

In vivo studies confirm its anti-cancer action as well as a complete absence of systemic toxicity in rodents8.


DIGESTIVE DISORDERS - Melano-glucan complexes have wide antimicrobial activity and I. obliquus has traditionally been used as an internal cleanser with Befungin, an alcohol extract of I. obliquus, licensed in Russia for the treatment of stomach and intestinal disorders9,23.


PSORIASIS - Several anecdotal reports indicate benefit of I. obliquus for psoriasis and this is supported by a Russian study on 50 psoriasis patients, which reported a 76% cure rate, with improvement in a further 16% of cases. The same study reported that it typically took 9-12 weeks for improvement to become apparent24.

l
ANTI-VIRAL- I.obliquus has traditionally been used to treat a number of viral conditions and aqueous extracts of I.obliquus prevented Herpes simplex virus entry through inhibition of viral-induced membrane fusion with a 50% inhibitory concentration of 3.82 μg/ml25. Betulinic acid analogs have also been shown to disrupt assembly and budding of the HIV-1 virus and viral fusion to the cell membrane.

 

CLINICAL SUMMARY
Main Therapeutic Applications - Cancer, anti-viral, antioxidant.
Key Component - Polysaccharides, betulin and betulinic acid derivatives.
Dose - It is reported that only aqueous extracts prepared by boiling, as done traditionally, show anti-tumour activity26. However, the level of triterpenes in pure aqueous extracts is low and many practitioners prefer to combine aqueous and ethanolic extracts. Average dosage for aqueous extracts as powder is 1-3g/day.


SAFETY - I.obliquus contains high oxalate concentrations and there is one report of a 72-year-old Japanese woman diagnosed with liver cancer who developed oxalate nephropathy after consuming 4-5 teaspoons a day of I.obliquus powder for 6 months27.

 

REFERENCES

1. Plants used against cancer. Hartwell JL. 1982. Quartermain Pubs: Lawrence, Mass. p.694.
2. Quality characteristics of rice inoculated with Inonotus obliquus mycelia and incubated under different cultivating conditions. Afr J Biotech. 2013;12(33):5131-5139.
3. Betulinic acid, a potent inhibitor of eukaryotic topoisomerase I: identification of the inhibitory step, the major functional group responsible and development of more potent derivatives. Chowdhury AR,Mandal S,Mittra B, Sharma S, Mukhopadhyay S, Majumder HK. Medical Science Monitor. 2002;8(7):254–65
4. Antimalarial activity of betulinic acid and derivatives in vitro against Plasmodium falciparum and in vivo in P. berghei-infected mice. de Sá MS, Costa JF, Krettli AU, Zalis MG, Maia GL, Sette IM, Câmara CdeA, Filho JM, Giulietti-Harley AM, Ribeiro Dos Santos R, Soares MB. Parasitol Res. 2009;105(1): 275-9
5. Solubility studies of oleanolic acid and betulinic acid in aqueous solutions and plant extracts of Viscum album L. Jäger S,Winkler K, Pfüller U, Scheffler A. Planta Med. 2007;73(2):157-62.
6. Antioxidant small phenolic ingredients in Inonotus obliquus (persoon) Pilat (Chaga). Nakajima Y, Sato Y, Konishi T. Chem Pharm Bull (Tokyo). 2007;55(8):1222-6.
7. Melanin complex from medicinal mushroom Inonotus obliquus (Pers.: Fr.) Pilat (Chaga) (Aphyllophoromycetideae). Bisko NA, Mitropolskaya NY, Ikonnikova NV. Int J Med Mushr. 2002;4(2):139-145.
8. Anti-inflammatory and anticancer activities of extracts and compounds from the mushroom Inonotus obliquus. Ma L, Chen H, Dong P, Lu X. Food Chem. 2013 Aug 15;139(1-4):503-8.
9. The Chaga Storey. Spinosa R. 2006. The Mycophile, 47:1.
10. In vitro antitumor activity and structure characterization of ethanol extracts from wild and cultivated Chaga medicinal mushroom, Inonotus obliquus (Pers.:Fr.) Pilát (Aphyllophoromycetideae). Sun Y, Yin T, Chen XH, Zhang G, Curtis RB, Lu ZH, Jiang JH. Int J Med Mushr. 2011;13(2):121-30.
11. Immunostimulating activity by polysaccharides isolated from fruiting body of Inonotus obliquus.Won DP, Lee JS, Kwon DS, Lee KE, Shin WC, Hong EK.Mol Cells. 2011 Feb;31(2):165-73.
12. Anticancer Effects of Fraction Isolated from Fruiting Bodies of Chaga Medicinal Mushroom, Inonotus obliquus (Pers.:Fr.) Pilát (Aphyllophoromycetideae): In Vitro Studies. Lemieszek MK, Langner E, Kaczor J, Kandefer-Szerszen M, Sanecka B, Mazurkiewicz W, RzeskiW. Int JMedMushr. 2011;13(2):131-143
13. Antitumor and immunomodulatory activity of water-soluble polysaccharide from Inonotus obliquus. Fan L, Ding S, Ai L, Deng K. Carbohydr Polym. 2012 Oct 1;90(2):870-4.
14. Progress on understanding the anticancer mechanisms of medicinal mushroom: Inonotus obliquus. Song FQ, Liu Y, Kong XS, Chang W, Song G.Asian Pac J Cancer Prev. 2013;14(3): 1571-8.
15. Betulinic acid, a natural compound with potent anticancer effects. Mullauer FB, Kessler JH,Medema JP.Anticancer Drugs. 2010;21(3):215-27. 2010;24(1):90-114.
16. BetulinicAcid as a potent and complex antitumor phytochemical: a minireview. Gheorgheosu D, Duicu O, Dehelean C, Soica C, Muntean D.Anticancer Agents Med Chem. 2014;14(7):936-45.
17. Betulinic acid induces apoptosis in human neuroblastoma cell lines. Schmidt ML, Kuzmanoff KL, Ling-Indeck L, Pezzuto JM. European Journal of Cancer. 1997;33(12):2007–10.
18. Chemistry, biological activity, and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infection.Cichewicz RH,Kouzi SA. Med Res Rev. 2004;24(1):90-114.
19. Betulinic acid: a new cytotoxic agent against malignant brain tumour cells. Fulda S, Jeremias I, Steiner HH, Pietsch T, Debatin KM. Int J Cancer. 1999;82(3):435-41.
20. Inhibitory Effects of a Polysaccharide Extract from the Chaga Medicinal Mushroom, Inonotus obliquus (Higher Basidiomycetes), on the Proliferation of Human Neurogliocytoma Cells. Ning XB, Qi Luo Q, Li C, Ding ZY, Pang J, Zhao C. Int J Med Mushr. 2014;16(1):29-36.
21. Effects of betulinic acid alone and in combination with irradiation in human melanoma cells. Selzer E, Pimentel E,WacheckV, et al. The Journal of Investigative Dermatology. 2000;114(5):935–40.
22. Betulinic acid - a radiosensitizer in head and neck Squamous cell carcinoma cell lines.  Eder-Czembirek C, Erovic BM, Czembirek C, Brunner M, Selzer E, Pötter R,Thurnher D. Strahlenther Onkol. 2010.
23. Medicinal plants of the Russian Pharmacopoeia; their history and applications. Shikov AN, Pozharitskaya ON, Makarov VG, Wagner H, Verpoorte R, Heinrich M. J Ethnopharmacol. 2014
Jul 3;154(3):481-536.
24. Treatment of Psoriasis with Using Chaga Mushroom Preparations. Dosychev EA, Bystrova VN. 1973. Vestn Dermatol Venerol. May;47(5):79-83.
25. Aqueous extract from a Chaga medicinal mushroom, Inonotus obliquus (higher Basidiomycetes), prevents herpes simplex virus entry through inhibition of viral-induced membrane fusion. Pan
HH et al. Int J Med Mushr. 2013;15(1):29-38.
26. Medicinal Mushrooms. An exploration of tradition, healing and culture. Hobbs C. 1986. Pub Botanica Press,Williams.
27. Chaga mushroom-induced oxalate nephropathy. Kikuchi Y, Seta K, Ogawa Y, Takayama T, Nagata M, Taguchi T,