Mesima – Phellinus linteus

Japanese nameMeshimakobu
Chinese nameSang Huang (Mulberry Yellow)

P. linteus is a basidiomycete fungus, popular in China, Korea and Japan and reported to work as a ‘miracle medicine’, prolonging longevity. Identified by Ikekawa as having the highest anti-tumour activity of the Hymenochaetales1 (a fungal order containing the major medicinal mushrooms), and by Stamets as having the greatest macrophage activation of 7 species surveyed2, it has been heavily researched in the last decade, especially in Korea, showing broad immunostimulant activity, strong anti-cancer properties and the ability to enhance the efficacy of existing chemotherapeutic drugs3.
Uniquely among the medicinal mushrooms, the Chinese Pharmacopoeia describes the energy of P. linteus as Cold and ascribes to it an extensive range of indications, including: cancer, diabetes, HIV, angina, leucorrhoea, diarrhoea and accelerated wound healing.
Research has focused on P. linteus’ polysaccharide and proteoglycan components although it also contains a number of flavonoid-like polyphenol pigments with antioxidant, anti-inflammatory, cytotoxic and anti-viral effects4.

CANCER – Interest in the potential of P. linteus in cancer therapy has been stimulated by recent reports of remarkable effects in a number of cancer patients taking it. One case reported dramatic remission in a hormone refractory prostate cancer with rapidly progressive bone metastasis5, while in a second a 65 year old man with a large hepatocellular cancer and metastasis in the skull, sternum and ribs, who declined all treatment except radiation for the painful frontal bone mass in favour of P. linteus, experienced spontaneous regression of the tumours6. In a third case spontaneous regression of hepatocellular cancer with multiple lung metastasis was linked to consumption of P. linteus mycelium (no conventional therapy undertaken)7.
In vitro studies show that low levels of P. linteus polysaccharides induce cell cycle arrest in lung cancer cells8 and exhibit synergistic action with chemotherapeutic drugs such as doxorubicin, inducing apoptosis at a sub-therapeutic dose in prostate and lung cancer cells9, while at high doses activating apoptosis in lung cancer cells, hormone sensitive and, to a lesser degree, refractory prostate cancer cells, as well as suppressing growth, angiogenesis and invasive behaviour of breast cancer cells10,11. Modes of action identified include inhibition of Akt signalling and caspase induction.
In vitro studies also show significant inhibition of bladder cancer cell growth with enhanced cytotoxic activity in combination with vitamin C12.
In vivo studies show significantly prolonged survival, reduced tumour growth and reduced frequency of lung metastasis in mice transplanted with melanoma cells after administration of polysaccharide extract13,14.

RHEUMATOID ARTHRITIS – In a murine rheumatoid arthritis model polysaccharide extract from P. linteus fruiting bodies reduced expression of pro-inflammatory Th2 cytokines (such as TNF-α and IFN-γ) and increased expression of anti-inflammatory Th1 cytokines, including IL-10 and TGF-β, resulting in the subsidence of the autoimmune response in the joints of the mice. Similar results were seen with polysaccharides from the related species Phellinus rimosus15,16.
P. linteus polysaccharides have also been shown to reduce expression of TNF-α and major histocompatability complex II expression in lipopolysaccharide induced septic shock, supporting their use as anti-inflammatory agents17.

ALLERGIES – Several studies show strong effect of P. linteus polysaccharides in suppressing production of Th2 cytkines and promoting secretion of Th1 cytokines, thereby addressing the immune imbalance involved in allergic responses18-20.At the same time it is reported that aqueous extract of P. linteus fruiting body prevented histamine release in response to allergenic stimuli and inhibited mast cell mediated anaphylaxis-like reactions21.
Other atopic conditions have also shown benefit from P. linteus in animal models including asthma and dermatitis22,23.

INFERTILITYP. linteus shows considerable promise in cases where infertility is associated with elevated cytokine and NK cell levels, with 23 of 26 women in one study showing improvement in immune parameters from supplementation with mycelial biomass at 3g/day24.

CLINICAL SUMMARY
Therapeutic Application – Cancer, rheumatoid arthritis, allergies.
Key Component – Polysaccharides.
Dose – The Chinese Pharmacopoeia prescribes a daily dose of 10-30g for the dried mushroom, while for polysaccharide extract 2-3g/day is usual25.

REFERENCES
1. Antitumour activity of some basidiomycetes, especially Phellinus linteus. Ikekawa T, Nakanishi M, Uehara N, Chihara G, Fukuoka F. Jpn J Cancer Res. 1968;59(2):155–157.
2. Potentiation of cell-mediated host defense using fruit bodies and mycelia of medicinal mushrooms. Stamets P. Int J Med Mushrooms. 2003;5(2):179–191.
3. A medicinal mushroom: Phellinus linteus. Zhu TB, Kim SH, Chen CY. Curr Med Chem. 2008;15(13):1330–1335.
4. Styrylpyrone-class compounds from medicinal fungi Phellinus and Inonotus spp., and their medicinal importance. Lee IK, Yun BS. J Antibiot. 2011;64(5):349–359.
5. Dramatic remission of hormone refractory prostate cancer achieved with extract of the mushroom, Phellinus linteus. Shibata Y, Kurita S, Okugi H, Yamanaka H. Urol Int. 2004;73(2):188–190.
6. Spontaneous regression of a large hepatocellular carcinoma with skull metastasis. Nam SW, Han JY, Kim JI, Park SH, Cho SH, Han NI, Yang JM, Kim JK, Choi SW, Lee YS, Chung KW, Sun HS. J Gastroenterol Hepatol. 2005;20(3):488–492.
7. A case of spontaneous regression of hepatocellular carcinoma with multiple lung metastases. Kojima H, Tanigawa N, Kariya S, Komemushi A, Shomura Y, Sawada S, Arai E, Yokota Y. Radiat Med. 2006;24(2):139–142.
8. Modulation of lung cancer growth arrest and apoptosis by Phellinus linteus. Guo J, Zhu T, Collins L, Xiao ZX, Kim SH, Chen CY. Mol Carcinog. 2007;46(2):144–154.
9. Phellinus linteus sensitises apoptosis induced by doxorubicin in prostate cancer. Collins L, Zhu T, Guo J, Xiao ZJ, Chen CY. Br J Cancer. 2006;95(3):282–288.
10. Phellinus linteus activates different pathways to induce apoptosis in prostate cancer cells. Zhu T, Guo J, Collins L, Kelly J, Xiao ZJ, Kim SH, Chen CY. Br J Cancer. 2007;96(4):583–590.
11. Phellinus linteus suppresses growth, angiogenesis and invasive behaviour of breast cancer cells through the inhibition of AKT signalling. Sliva D, Jedinak A, Kawasaki J, Harvey K, Slivova V. Br J Cancer. 2008;98(8): 1348–1356.
12. Effect of various natural products on growth of bladder cancer cells: two promising mushroom extracts. Konno S. Altern Med Rev. 2007;12(1):63–68.
13. Acidic polysaccharide from Phellinus linteus inhibits melanoma cell metastasis by blocking cell adhesion and invasion. Han SB, Lee CW, Kang JS, Yoon YD, Lee KH, Lee K, Park SK, Kim HM. Int Immunopharmacol. 2006;6(4):697–702.
14. The inhibitory effect of polysaccharide isolated from Phellinus linteus on tumour growth and metastasis. Han B, Lee CW, Jeon YJ, Hong ND, Yoo ID, Yang KH, Kim HM. Immunopharmacology. 1999;41(2):157–164.
15. Oral administration of proteoglycan isolated from Phellinus linteus in the prevention and treatment of collagen-induced arthritis in mice. Kim GY, Kim SH, Hwang SY, Kim HY, Park YM, Park SK, Lee MK, Lee SH, Lee TH, Lee JD. Biol Pharm Bull. 2003;26(6):823–831.
16. Antiarthritic activity of a Polysaccharide-protein complex isolated from Phellinus rimosus (Berk.) Pilát (Aphyllophoromycetideae) in Freund’s complete adjuvant-induced arthritic rats. Meera CR, Smina TP, Nitha B, Mathew J, Janardhanan KK. Int J Med Mushrooms. 2009;11(1):21–28.
17. Alleviation of experimental septic shock in mice by acidic polysaccharide isolated from the medicinal mushroom Phellinus linteus. Kim GY, Roh SI, Park SK, Ahn SC, Oh YH, Lee JD, Park YM. Biol Pharm Bull. 2003;26(10):1418–1423.
18. Stimulation of humoral and cell mediated immunity by polysaccharide from mushroom Phellinus linteus. Kim HM, Han SB, Oh GT, Kim YH, Hong DH, Hong ND, Yoo ID. Int J Immunopharmacol. 1996;18(5):295–303.
19. Phellinus linteus extract augments the immune response in Mitomycin C-induced immunodeficient mice. Matsuba S, Matsuno H, Sakuma M, Komatsu Y. Evid Based Complement Alternat Med. 2008;5(1):85–90.
20. Phellinus linteus grown on germinated brown rice suppresses IgE production by the modulation of Th1/Th2 balance in murine mesenteric lymph node lymphocytes. Lim BO, Jeon TI, Hwang SG, Moon JH, Park DK. Biotechnol Lett. 2005;27(9):613–617.
21. Inhibition of anaphylaxis-like reaction and mast cell activation by water extract from the fruiting body of Phellinus linteus. Choi YH, Yan GH, Chai OH, Lim JM, Sung SY, Zhang X, Kim JH, Choi SH, Lee MS, Han EH, Kim HT, Song CH. Biol Pharm Bull. 2006;29(7):1360–1365.
22. Immunomodulatory effect of water soluble extract separated from mycelium of Phellinus linteus on experimental atopic dermatitis. Hwang JS, Kwon HK, Kim JE, Rho J, Im SH. BMC Complement Altern Med. 2012;12:159.
23. Phellinus linteus extract exerts anti-asthmatic effects by suppressing NF-κB and p38 MAPK activity in an OVA-induced mouse model of asthma. Yan GH, Choi YH. Immune Netw. 2014;14(2):107–115.
24. Wings T: Immune-Related Female Infertility. TCM Kongress Rothenburg 2012.
25. Chinese Pharmacopoeia, 2010. Beijing : Chinese Medicine Science and Technology Publishing House, 2010.