Phellinus linteus

• How It Works

  Phellinus linteus, a medicinal mushroom, showed anticancer effects in lab studies. Clinical trials are needed to establish its anticancer potential.

  P. linteus is a medicinal mushroom used in traditional medicine in Asia. Compounds present in this mushroom have been shown in the lab to have anti-inflammatory and antitumor properties. However, evidence in humans is very limited. There is one study that suggests it maybe helpful as an add-on treatment in some pancreatic cancer patients. Well-designed trials are needed to confirm these effects.

• Purported Uses

  To inhibit tumor growth
  P. linteus has been shown in some lab studies to inhibit tumor growth. One study in pancreatic cancer patients suggest it may be helpful as an add-on therapy. There are also a few cases of regression of liver and prostate cancers. Well-designed studies are needed to confirm such effects.

• Side Effects

  P. linteus use resulted in worsening of an autoimmune condition called pemphigus that is characterized by blisters on the skin and mucous membranes and by itching or burning.

• Scientific Name

  Phellinus linteus

• Clinical Summary

  Phellinus linteus (PL) is a yellow, bitter-tasting mushroom that grows on mulberry trees. It is used in traditional medicine in Asia where it is often mixed with other medicinal mushrooms, such as Reishi and Maitake, and promoted as an adjunctive treatment during cancer therapy. It also has traditional applications in the treatment of hemorrhage, hemostasis, and menstrual disorders ⁽²⁷⁾.

  The polysaccharide-protein complexes found in PL were shown to have immunomodulating effects ⁽¹⁾. In animal models, the polyphenolic constituent demonstrated anti-inflammatory properties, which may protect against injury and other syndromes involving infarcts, hematomas or hemorrhages ^(2) (3). Other constituents, such as interfungins A, help prevent protein modification in hyperglycemic state, and may benefit diabetics ⁽⁴⁾.

  PL extracts have exhibited anticancer effects in a variety of human cancer cell lines  ⁽²⁸⁾. In vitro and animal studies suggest that it has antiangiogenic, antioxidant, and xanthine oxidase inhibition properties ⁽⁵⁾. Anticancer effects against breast ^{(6) (7) (8)}, colon ^{(9) (10) (30)}, liver ⁽¹¹⁾, lung ^(12) (13), oral ⁽¹⁴⁾, prostate ^{(15) (16) (17)}, and skin cancers ^{(1) (18) (19)} have also been reported. In addition, PL and its constituents have exhibited chemosensitizing effects in pancreatic and colon cancer cells ^(29) (31).

  In a study of pancreatic cancer patients, PL appeared to improve outcomes in part by improving adherence to adjuvant chemotherapy ⁽³²⁾. There are also a few case reports of tumor regression following consumption of PL ^{(11) (20) (21)}. However, well-designed trials are needed to confirm these effects.

• Purported Uses
  • Anti-hemorrhagic
  • Anti-inflammatory
  • Cancer treatment 
• Mechanism of Action

  Polysaccharide-protein complexes found in PL have immunomodulating ⁽¹⁾, antiangiogenic, antioxidant and xanthine oxidase inhibition effects ⁽⁵⁾. Additionally, the furopyranone compounds inhibit protein glycation, which may aid in treatment and prevention of diabetic complications ^(4) (23). In non-obese diabetic mice, a PL-polysaccharide extract enhanced function of macrophages, as well as dendritic, NK, T, and B cells, and prevented inflammation by inhibiting IFNγ, IL2, and TNFα via TH1 cells and macrophages. It also upregulated IL4 expression in TH2 cells  ⁽²³⁾.

  Anti-inflammatory activities of inotilone, a compound isolated from PL might be due to reduced levels of malondialdehyde, inducible nitric oxide synthase, COX2, NFκB, and MMP9, as well as increased activities of catalase, superoxide dismutase, and glutathione peroxidase via TNFα and NO suppression ⁽²⁵⁾.

  Hispidin, a phenolic compound present in PL, was shown to protect against peroxynitrite-mediated cytotoxicity, DNA damage and hydroxyl radical formation ⁽²⁶⁾. PL also inhibited proliferation in human colon cancer cells via decreased Bcl2 and cyclin B1 and increased cytochrome C ⁽⁹⁾. Another study similarly found that a PL extract induced G0/G1 arrest and apoptosis in human colon carcinoma HT29 cells via p21(C1P1/WAF1) upregulation, cyclin D1 downregulation, Bcl2 downregulation, release of cytochrome C, and activation of caspases 9, 3, and 8 ⁽¹⁰⁾. Decreased cyclin-dependent kinases CDK2, 4, and 6, and dose-dependent apoptosis of lung cancer cells after treatment with PL were also observed ⁽¹²⁾.

• Adverse Reactions

  Case Report

  • Exacerbation of the autoimmune disorder pemphigus: Following use of PL ⁽²⁴⁾.
• References

  1. Kim GY LJ, Lee JO, Ryu CH, Choi BT, Jeong YK, Lee KW, Jeong SC, Choi YH. Partial characterization and immunostimulatory effect of a novel polysaccharide-protein complex extracted from Phellinus linteus. Biosci Biotechnol Biochem. May 2006;70(5):1218-1226.

  2. Chang HY SM, Yang CH, Lu TC, Chang YS, Peng WH, Huang SS, Huang GJ. Analgesic Effects and the Mechanisms of Anti-Inflammation of Hispolon in Mice. Evid Based Complement Alternat Med. Apr 6. 2009

  3. Suzuki S KT, Okada Y, Kobayashi T, Nakamura T, Hori T. Filtrate of Phellinus linteus Broth Culture Reduces Infarct Size Significantly in a Rat Model of Permanent Focal Cerebral Ischemia. Evid Based Complement Alternat Med. Jan 20. 2009.

  4. Lee YS KY, Jung JY, Lee S, Ohuchi K, Shin KH, Kang IJ, Park JH, Shin HK, Lim SS. Protein glycation inhibitors from the fruiting body of Phellinus linteus. Biol Pharm Bull. Oct 31 2008;31(10):1968-1972.

  5. Song YS, Kim SH, Sa JH, Jin C, Lim CJ, Park EH. Anti-angiogenic, antioxidant and xanthine oxidase inhibition activities of the mushroom Phellinus linteus. J Ethnopharmacol. Sep 2003;88(1):113-116.

  6. Sliva D, Jedinak A, Kawasaki J, Harvey K, Slivova V. Phellinus linteus suppresses growth, angiogenesis and invasive behaviour of breast cancer cells through the inhibition of AKT signalling. Br J Cancer. 2008 Apr 22;98(8):1348-56.

  7. Lu TL HG, Lu TJ, Wu JB, Wu CH, Yang TC, Iizuka A, Chen YF. Hispolon from Phellinus linteus has antiproliferative effects via MDM2-recruited ERK1/2 activity in breast and bladder cancer cells. Food Chem Toxicol. Aug 2009;47(8):2013-2021.

  8. Sliva D JA, Kawasaki J, Harvey K, Slivova V. Phellinus linteus suppresses growth, angiogenesis and invasive behaviour of breast cancer cells through the inhibition of AKT signalling. Br J Cancer. Apr 22 2008;98(8):1348-1356.

  9. Li G KD, Kim TD, Park BJ, Park HD, Park JI, Na MK, Kim HC, Hong ND, Lim K, Hwang BD, Yoon WH. Protein-bound polysaccharide from Phellinus linteus induces G2/M phase arrest and apoptosis in SW480 human colon cancer cells. Cancer Lett. Dec 28 2004;216(2):175-181.

  10. Park HJ CS, Hong SM, Hwang SG, Park DK. The ethyl acetate extract of Phellinus linteus grown on germinated brown rice induces G(0)/G(1) cell cycle arrest and apoptosis in human colon carcinoma HT29 cells. Phytother Res. 2010 Jul;24(7):1019-26.

  11. Nam SW, Han JY, Kim JI, et al. Spontaneous regression of a large hepatocellular carcinoma with skull metastasis. J Gastroenterol Hepatol. Mar 2005;20(3):488-492.

  12. Guo J ZT, Collins L, Xiao ZX, Kim SH, Chen CY. Modulation of lung cancer growth arrest and apoptosis by Phellinus Linteus. Mol Carcinog. Feb 2007;46(2):144-154.

  13. Mukai M KA, Hiramatsu N, Hayakawa K, Okamura M, Tagawa Y, Yao J, Nakamura T, Kitamura M. Blockade of the aryl hydrocarbon receptor pathway triggered by dioxin, polycyclic aromatic hydrocarbons and cigarette smoke by Phellinus linteus. Biol Pharm Bull. Oct 2008;31(10):1888-1893.

  14. Chen W HF, Li YQ. The apoptosis effect of hispolon from Phellinus linteus (Berkeley & Curtis) Teng on human epidermoid KB cells. J Ethnopharmacol. Apr 21 2006;105(1-2):280-285.

  15. Collins L ZT, Guo J, Xiao ZJ, Chen CY. Phellinus linteus sensitises apoptosis induced by doxorubicin in prostate cancer. Br J Cancer. Aug 7 2006;95(3):282-288.

  16. Tsuji T DW, Nishioka T, Chen L, Yamamoto D, Chen CY. Phellinus linteus extract sensitizes advanced prostate cancer cells to apoptosis in athymic nude mice. PLoS One. Mar 31 2010;5(3):e9885.

  17. Zhu T GJ, Collins L, Kelly J, Xiao ZJ, Kim SH, Chen CY. Phellinus linteus activates different pathways to induce apoptosis in prostate cancer cells. Br J Cancer. Feb 26 2007;96(4):583-590.

  18. Han SB LC, Kang JS, Yoon YD, Lee KH, Lee K, Park SK, Kim HM. Acidic polysaccharide from Phellinus linteus inhibits melanoma cell metastasis by blocking cell adhesion and invasion. Int Immunopharmacol. Apr 2006;6(4):697-702.

  19. Lee HJ LH, Lim ES, Ahn KS, Shim BS, Kim HM, Gong SJ, Kim DK, Kim SH. Cambodian Phellinus linteus inhibits experimental metastasis of melanoma cells in mice via regulation of urokinase type plasminogen activator. Biol Pharm Bull. Jan 2005;28(1):27-31.

  20. Shibata Y, Kurita S, Okugi H, Yamanaka H. Dramatic remission of hormone refractory prostate cancer achieved with extract of the mushroom, Phellinus linteus. Urol Int. 2004;73(2):188-190.

  21. Kojima H TN, Kariya S, Komemushi A, Shomura Y, Sawada S, Arai E, Yokota Y. A case of spontaneous regression of hepatocellular carcinoma with multiple lung metastases. Radiat Med. Feb 2006;24(2):139-142.

  22. Kojima K OT, Inoue M, Mizukami H, Nagatsu A. Phellifuropyranone A: a new furopyranone compound isolated from fruit bodies of wild Phellinus linteus. Chem Pharm Bull (Tokyo). Feb 2008;56(2):173-175.

  23. Kim HM KJ, Kim JY, Park SK, Kim HS, Lee YJ, Yun J, Hong JT, Kim Y, Han SB. Evaluation of antidiabetic activity of polysaccharide isolated from Phellinus linteus in non-obese diabetic mouse. Int Immunopharmacol. Jan 2010;10(1):72-78.

  24. Jin SP, Hong JS, Chung JH. Exacerbation of pemphigus following Phellinus linteus ingestion. J Eur Acad Dermatol Venereol. 2011 Apr;25(4):492-3.

  25. Huang GJ, Huang SS, Deng JS. Anti-inflammatory activities of inotilone from Phellinus linteus through the inhibition of MMP-9, NF-κB, and MAPK activation in vitro and in vivo. PLoS One. 2012;7(5):e35922.

  26. Chen W, Feng L, Huang Z, Su H. Hispidin produced from Phellinus linteus protects against peroxynitrite-mediated DNA damage and hydroxyl radical generation.Chem Biol Interact. 2012 Sep 30;199(3):137-42.

  27. Chen H, Tian T, Miao H, et al. Traditional uses, fermentation, phytochemistry and pharmacology of Phellinus linteus: A review. Fitoterapia. Sep 2016;113:6-26.

  28. Konno S, Chu K, Feuer N, et al. Potent Anticancer Effects of Bioactive Mushroom Extracts (Phellinus linteus) on a Variety of Human Cancer Cells. J Clin Med Res. Feb 2015;7(2):76-82.

  29. Chandimali N, Huynh DL, Jin WY, et al. Combination Effects of Hispidin and Gemcitabine via Inhibition of Stemness in Pancreatic Cancer Stem Cells. Anticancer Res. Jul 2018;38(7):3967-3975.

  30. Lim JH, Lee YM, Park SR, et al. Anticancer activity of hispidin via reactive oxygen species-mediated apoptosis in colon cancer cells. Anticancer Res. Aug 2014;34(8):4087-4093.

  31. Yu T, Ganapathy S, Shen L, et al. A lethal synergy induced by Phellinus linteus and camptothecin11 in colon cancer cells. Oncotarget. Jan 19 2018;9(5):6308-6319.

  32. Lee SH, Hwang HK, Kang CM, et al. Potential Impact of Phellinus linteus on Adherence to Adjuvant Treatment After Curative Resection of Pancreatic Ductal Adenocarcinoma: Outcomes of a Propensity Score-Matched Analysis. Integr Cancer Ther. Jan-Dec 2019;18:1534735418816825.