Misconstrued versatility of Ganoderma lucidum: a key player in multi-targeted cellular signaling

Tumor Biology

Volumn 37, Issue 3, 2016, Pages 2789-2804

  Gill, Balraj Singh ^a   Sharma, Prateek ^a   Kumar, Raj ^a   Kumar, Sanjeev ^a  

^a CENTRAL UNIVERSITY OF PUNJAB   (India)

Author keywords

Cancer; Ganoderic acid (GA); Ganoderma lucidum; Polysaccharides; Terpenoids

Indexed keywords

ALCOHOL DERIVATIVE; ANTINEOPLASTIC AGENT; ANTIOXIDANT; DNA TOPOISOMERASE; FUNGAL PROTEIN; GANODERIC ACID; GANODERMANONTRIOL; HERBACEOUS AGENT; IMMUNOMODULATING AGENT; LZ 8 PROTEIN; MICROSPHERULE 58 PROTEIN; NANOPARTICLE; POLYSACCHARIDE; TERPENE; UNCLASSIFIED DRUG; IMMUNOLOGIC FACTOR;

ANTINEOPLASTIC ACTIVITY; ANTIOXIDANT ACTIVITY; APOPTOSIS; BIOLOGICAL ACTIVITY; BLOATING; CLINICAL EFFECTIVENESS; DOWN REGULATION; DRUG DELIVERY SYSTEM; DRUG DETERMINATION; DRUG EFFECT; DRUG EFFICACY; DRUG FORMULATION; DRUG MECHANISM; DRUG SAFETY; DRUG STRUCTURE; DRUG TOLERABILITY; ENZYME INHIBITION; FUNGUS IDENTIFICATION; GANODERMA LUCIDUM; HUMAN; IMMUNOMODULATION; MULTIDRUG RESISTANCE; NONHUMAN; PHYTOCHEMISTRY; POLLAKISURIA; PRIORITY JOURNAL; PROTEIN DETERMINATION; PROTEIN FUNCTION; RASH; REVIEW; SIGNAL TRANSDUCTION; SOMNOLENCE; ANIMAL; CHEMISTRY; DRUG EFFECTS;

ANIMALS; ANTINEOPLASTIC AGENTS; ANTIOXIDANTS; APOPTOSIS; HUMANS; IMMUNOLOGIC FACTORS; POLYSACCHARIDES; REISHI; SIGNAL TRANSDUCTION; TERPENES;

EID: 84952066998     PISSN: 10104283     EISSN: 14230380     Source Type: Journal    
DOI: 10.1007/s13277-015-4709-z     Document Type: Review

References (160)

1. Correia-da-Silva M, Sousa E, Pinto MM. Emerging sulfated flavonoids and other polyphenols as drugs: nature as an inspiration. Med Res Rev. 2013;34(2):223–79.
2. Tavakoli J, Miar S, Zadehzare MM, Akbari H. Evaluation of effectiveness of herbal medication in cancer care: a review study. Iran J Cancer Prev. 2012;5(3):144–56.
3. Moncalvo J. Systematics of Ganoderma 2. In: Flood J, Bridge PD, Holderness M, editors. Ganoderma diseases of perennial crops. U.S.A: CBAI Publishing; 2000. p. 23.
4. Bhosle S, Ranadive K, Bapat G, Garad S, Deshpande G, Vaidya J. Taxonomy and diversity of Ganoderma from the Western parts of Maharashtra (India). Mycosphere. 2010;1(3):249–62.
5. Jones K. Reishi mushroom: ancient medicine in modern times. J Altern Complement Med. 1998;4(4):256–66.
6. Cao Y, Wu S-H, Dai Y-C. Species clarification of the prize medicinal Ganoderma mushroom “Lingzhi”. Fungal Divers. 2012;56(1):49–62.
7. Xu Z, Chen X, Zhong Z, Chen L, Wang Y. Ganoderma lucidum polysaccharides: immunomodulation and potential anti-tumor activities. Am J Chin Med. 2011;39(01):15–27.
8. Kao C, Jesuthasan AC, Bishop KS, Glucina MP, Ferguson LR. Anti-cancer activities of Ganoderma lucidum: active ingredients and pathways. Funt Foods Health Dis. 2013;3(2):48–65.
9. Fan L, Li J, Deng K, Ai L. Effects of drying methods on the antioxidant activities of polysaccharides extracted from Ganoderma lucidum. Carbohydr Polym. 2012;87(2):1849–54.
10. Pan D, Zhang D, Wu J, Chen C, Xu Z, Yang H, et al. A novel proteoglycan from Ganoderma lucidum fruiting bodies protects kidney function and ameliorates diabetic nephropathy via its antioxidant activity in C57BL/6 db/db mice. Food Chem Toxicol. 2014;63:111–8.
11. Cilerdzic J, Stajic M, Vukojevic J, Duletic-Lausevic S. Oxidative stress and species of genus Ganoderma (higher Basidiomycetes). Int J Med Mushroom. 2013;15(1):21–8.
12. Sakthivigneswari G, Dharmaraj K. Studies on analysis of few secondary metabolites and antimicrobial activity of Ganoderma lucidum. J Pharm Res. 2013;1(8).
13. Guillamón E, García-Lafuente A, Lozano M, Rostagno MA, Villares A, Martínez JA. Edible mushrooms: role in the prevention of cardiovascular diseases. Fitoterapia. 2010;81(7):715–23.
14. Aguirre-Moreno A, Campos-Pena V, del Rio-Portilla F, Herrera-Ruiz M, Leon-Rivera I, Montiel E, et al. Anticonvulsant and neuroprotective effects of oligosaccharides from Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum (higher Basidiomycetes). Int J Med Mushrooms. 2013;15(6):555–68.
15. Cheng P-G, Phan C-W, Sabaratnam V, Abdullah N, Abdulla MA, Kuppusamy UR. Polysaccharides-rich extract of Ganoderma lucidum (MA Curtis: Fr.) P. Karst accelerates wound healing in streptozotocin-induced diabetic rats. J Evid Based Complement Altern Med. 2013;2013.
16. Kim HW, Kim BK. Biomedicinal triterpenoids of Ganoderma lucidum (Curt.: Fr.) P. Karst. (Aphyllophoromycetideae). Int J Med Mushrooms. 1999;1(2):121–8.
17. Mckenna D, Hughes K, Jones K. Botanical medicines: the desk reference for major herbal supplements (2002). New York: The Haworth Herbal Press; 2002.
18. Nasir N. Diseases caused by Ganoderma spp. on perennial crops in Pakistan. Mycopathologia. 2005;159(1):119–21.
19. Lee I, Ahn B, Choi J, Hattori M, Min B, Bae K. Selective cholinesterase inhibition by lanostane triterpenes from fruiting bodies of Ganoderma lucidum. Bioorg Med Chem Lett. 2011;21(21):6603–7.
20. Zhou Y, Qu ZQ, Zeng YS, Lin YK, Li Y, Chung P, et al. Neuroprotective effect of preadministration with Ganoderma lucidum spore on rat hippocampus. Exp Toxicol Pathol. 2012;64(7):673–80.
21. Zhang X-Q, Ip FC, Zhang D-M, Chen L-X, Zhang W, Li Y-L, et al. Triterpenoids with neurotrophic activity from Ganoderma lucidum. Nat Prod Rep. 2011;25(17):1607–13.
22. Huie CW, Di X. Chromatographic and electrophoretic methods for Lingzhi pharmacologically active components. J Chromatogr B. 2004;812(1):241–57.
23. Borchers AT, Stern JS, Hackman RM, Keen CL, Gershwin ME. Mushrooms, tumors, and immunity. Proc Soc Exp Biol Med. 1999;221(4):281–93.
24. Chen AW, Miles PG. Biomedical research and the application of mushroom nutriceuticals from Ganoderma lucidum. Mushroom Biol mushroom Prod. 1996:161–75.
25. Liu GT. Recent advances in research of pharmacology and clinical applications of Ganoderma P. Karst. species (Aphyllophoromycetideae) in China. Int J Med Mushrooms. 1999;1(1).
26. Yadav VR, Prasad S, Sung B, Kannappan R, Aggarwal BB. Targeting inflammatory pathways by triterpenoids for prevention and treatment of cancer. Toxins. 2010;2(10):2428–66.
27. Yue QX, Song XY, Ma C, Feng LX, Guan SH, Wu WY, et al. Effects of triterpenes from Ganoderma lucidum on protein expression profile of HeLa cells. Phytomedicine. 2010;17(8):606–13.
28. Liu J, Shiono J, Shimizu K, Kukita A, Kukita T, Kondo R. Ganoderic acid DM: anti-androgenic osteoclastogenesis inhibitor. Bioorg Med Chem Lett. 2009;19(8):2154–7.
29. Yao X, Li G, Xu H, Lü C. Inhibition of the JAK-STAT3 signaling pathway by ganoderic acid A enhances chemosensitivity of HepG2 Cells to cisplatin. Planta Med. 2012;78(16):1740–8.
30. Gill BS, Kumar S. Differential algorithms-assisted molecular modeling-based identification of mechanistic binding of ganoderic acids. Med Chem Res. 2015;24(9):3483–93.
31. Min B-S, Nakamura N, Miyashiro H, Bae KW, Hattori M. Triterpenes from the spores of Ganoderma lucidum and their inhibitory activity against HIV-1 protease. Chem Pharm Bull. 1998;46(10):1607–12.
32. Akbar R, Yam WK. Interaction of ganoderic acid on HIV related target: molecular docking studies. Bioinformation. 2011;7(8):413–7.
33. El-Mekkawy S, Meselhy MR, Nakamura N, Tezuka Y, Hattori M, Kakiuchi N, et al. Anti-HIV-1 and anti-HIV-1-protease substances from Ganoderma lucidum. Phytochemistry. 1998;49(6):1651–7.
34. Hirotani M, Furuya T. Ganoderic acid derivatives, highly oxygenated lanostane-type triterpenoids, from Ganoderma lucidum. Phytochemistry. 1986;25(5):1189–93.
35. Guesnet J, Guezennec L, Anne B. Use of ganoderic acids as cosmetic agents and for treating or preventing skin disorder. EP; 2003.
36. Deepalakshmi K, Mirunalini S. Therapeutic properties and current medical usage of medicinal mushroom: Ganoderma lucidum. Int J Pharm Sci Res. 2011;2:1922–9.
37. Thyagarajan A, Jedinak A, Nguyen H, Terry C, Baldridge LA, Jiang J, et al. Triterpenes from Ganoderma lucidum induce autophagy in colon cancer through the inhibition of p38 mitogen-activated kinase (p38 MAPK). Nutr Cancer. 2010;62(5):630–40.
38. Xu J-W, Zhao W, Zhong J-J. Biotechnological production and application of ganoderic acids. Appl Microbiol Biotechnol. 2010;87(2):457–66.
39. Chen N-H, Zhong J-J. Ganoderic acid Me induces G arrest in wild-type p53 human tumor cells while G/S transition arrest in p53-null cells. Process Biochem. 2009;44(8):928–33.
40. Zhou L, Shi P, Chen NH, Zhong J-J. Ganoderic acid Me induces apoptosis through mitochondria dysfunctions in human colon carcinoma cells. Process Biochem. 2011;46(1):219–25.
41. Kanda H, Da Y, Sakamoto M, Fujii M, Hirai Y, Yamazaki K. The biologically active constituents of Ganoderma lucidum (Fr.) Karst. Histamine release-inhibitory triterpenes. Chem Pharm Bull. 1985;33(4):1367–74.
42. Wasser SP. Reishi or Lingzhi (Ganoderma lucidum). Encycl Diet Suppl. 2005:603–22.
43. Wu GS, Lu JJ, Guo JJ, Li YB, Tan W, Dang YY, et al. Ganoderic acid DM, a natural triterpenoid, induces DNA damage, G1 cell cycle arrest and apoptosis in human breast cancer cells. Fitoterapia. 2012;83(2):408–14.
44. Sheena N, Ajith T, Janardhanan K. Anti-inflammatory and anti-nociceptive activities of Ganoderma lucidum occurring in South India. Pharm Biol. 2003;41(4):301–4.
45. Joseph S, Sabulal B, George V, Smina TP, Janardhanan KK. Antioxidative and antiinflammatory activities of the chloroform extract of Ganoderma lucidum found in South India. Sci Pharm. 2009;77:111–21.
46. Morigiwa A, Kitabatake K, Fujimoto Y, Ikekawa N. Angiotensin converting enzyme-inhibitory triterpenes from Ganoderma lucidum. Chem Pharm Bull. 1986;34(7):3025–8.
47. Hajjaj H, Macé C, Roberts M, Niederberger P, Fay LB. Effect of 26-oxygenosterols from Ganoderma lucidum and their activity as cholesterol synthesis inhibitors. Appl Environ Microbiol. 2005;71(7):3653–8.
48. Li C, Yin J, Guo F, Zhang D, Sun HH. Ganoderic acid Sz, a new lanostanoid from the mushroom Ganoderma lucidum. Nat Prod Res. 2005;19(5):461–5.
49. Tang W, Liu JW, Zhao WM, Wei DZ, Zhong JJ. Ganoderic acid T from Ganoderma lucidum mycelia induces mitochondria mediated apoptosis in lung cancer cells. Life Sci. 2006;80(3):205–11.
50. Liu RM, Zhong JJ. Ganoderic acid Mf and S induce mitochondria mediated apoptosis in human cervical carcinoma HeLa cells. Phytomedicine. 2011;18(5):349–55.
51. Chen NH, Liu JW, Zhong J-J. Ganoderic acid T inhibits tumor invasion in vitro and in vivo through inhibition of MMP expression. Pharmacol Rep. 2010;62(1):150.
52. Fatmawati S, Shimizu K, Kondo R. Inhibition of aldose reductase in vitro by constituents of Ganoderma lucidum. Planta Med. 2010;76(15):1691–3.
53. Ouyang JJ, Wang YQ, Tang W. Ganoderic acid restores the sensitivity of multidrug resistance cancer cells to doxorubicin. Adv Mat Res. 2014;834:573–6.
54. Liu RM, Li YB, Zhong J-J. Cytotoxic and pro-apoptotic effects of novel ganoderic acid derivatives on human cervical cancer cells in vitro. Eur J Pharmacol. 2012;681(1):23–33.
55. Li YQ, Wang SF. Anti-hepatitis B activities of ganoderic acid from Ganoderma lucidum. Biotechnol Lett. 2006;28(11):837–41.
56. Wang JL, Li YB, Qin HL, Zhong JJ. Kinetic study of 7-ethyl ganoderic acid O stability and its importance in the preparative isolation. Biochem Eng J. 2011;53(2):182–6.
57. Chen N-H, Zhong J-J. p53 is important for the anti-invasion of ganoderic acid T in human carcinoma cells. Phytomedicine. 2011;18(8):719–25.
58. Liu J, Shimizu K, Tanaka A, Shinobu W, Ohnuki K, Nakamura T, et al. Target proteins of ganoderic acid DM provides clues to various pharmacological mechanisms. Sci Rep. 2012;2.
59. JunXing L, XiaoGuang L, Lin W, Fei W, ZhiWei Y. Neuroprotective effects of ganoderic acid extract against epilepsy in primary hippocampal neurons. Res Opin Anim Vet Sci. 2013;3(11):420–5.
60. Fatmawati S, Shimizu K, Kondo R, Ganoderol B. A potent α-glucosidase inhibitor isolated from the fruiting body of Ganoderma lucidum. Phytomedicine. 2011;18(12):1053–5.
61. Eo SK, Kim YS, Lee CK, Han SS. Antiviral activities of various water and methanol soluble substances isolated from Ganoderma lucidum. J Ethnopharmacol. 1999;68(1):129–36.
62. De Silva DD, Rapior S, Sudarman E, Stadler M, Xu J, Alias SA, et al. Bioactive metabolites from macrofungi: ethnopharmacology, biological activities and chemistry. Fungal Divers. 2013;62(1):1–40.
63. Chen R, Yu D. Development of triterpenes from Ganoderma lucidum. Acta Pharm Sin. 1990;25:940–53.
64. Zhou X, Gong Z, Su Y, Lin J, Tang K. Cordyceps fungi: natural products, pharmacological functions and developmental products. J Pharm Pharmacol. 2009;61(3):279–91.
65. Kao CH, Jesuthasan AC, Bishop KS, Glucina MP, Ferguson LR. Anti-cancer activities of Ganoderma lucidum: active ingredients and pathways. Funct Foods Health Dis 2. 2013;3(2):48–65.
66. Feng L, Yuan L, Du M, Chen Y, Zhang M-H, Gu J-F, et al. Anti-lung cancer activity through enhancement of immunomodulation and induction of cell apoptosis of total triterpenes extracted from Ganoderma lucidum (Leyss. ex Fr.) Karst. Molecules. 2013;18(8):9966–81.
67. Lin S-B, Li C-H, Lee S-S, Kan L-S. Triterpene-enriched extracts from Ganoderma lucidum inhibit growth of hepatoma cells via suppressing protein kinase C, activating mitogen-activated protein kinases and G2-phase cell cycle arrest. Life Sci. 2003;72(21):2381–90.
68. Jiang J, Slivova V, Valachovicova T, Harvey K, Sliva D. Ganoderma lucidum inhibits proliferation and induces apoptosis in human prostate cancer cells PC-3. Int J Oncol. 2004;24(5):1093–9.
69. Lin Z-B. Cellular and molecular mechanisms of immuno-modulation by Ganoderma lucidum. J Pharmacol Sci. 2005;99(2):144–53.
70. Jiang J, Grieb B, Thyagarajan A, Sliva D. Ganoderic acids suppress growth and invasive behavior of breast cancer cells by modulating AP-1 and NF-κB signaling. Int J Mol Med. 2008;21(5):577–84.
71. Lokody I. Metabolism: cholesterol promotes breast cancer growth. Nat Rev Cancer. 2014;14(1):11.
72. Komoda Y, Shimizu M, Sonoda Y, Sato Y. Ganoderic acid and its derivatives as cholesterol synthesis inhibitors. Chem Pharm Bull. 1989;37(2):531–3.
73. Wu TS, Shi LS, Kuo SC. Cytotoxicity of Ganoderma lucidum triterpenes. J Nat Prod. 2001;64(8):1121–2.
74. Liu YW, Gao J-L, Guan J, Qian Z-M, Feng K, Li S-P. Evaluation of antiproliferative activities and action mechanisms of extracts from two species of Ganoderma on tumor cell lines. J Agric Food Chem. 2009;57(8):3087–93.
75. Chen NH, Liu JW, Zhong J-J. Ganoderic acid Me inhibits tumor invasion through down-regulating matrix metalloproteinases 2/9 gene expression. J Pharmacol Sci. 2008;108(2):212–6.
76. Gao JJ, Min BS, Ahn EM, Nakamura N, Lee HK, Hattori M. New triterpene aldehydes, lucialdehydes A—C, from Ganoderma lucidum and their cytotoxicity against murine and human tumor cells. Chem Pharm Bull. 2002;50(6):837–40.
77. Min BS, Gao JJ, Nakamura N, Hattori M. Triterpenes from the spores of Ganoderma lucidum and their cytotoxicity against meth-A and LLC tumor cells. Chem Pharm Bull. 2000;48(7):1026–33.
78. Zhu M, Chang Q, Wong LK, Chong FS, Li RC. Triterpene antioxidants from Ganoderma lucidum. Phytother Res. 1999;13(6):529–31.
79. Wang G, Zhao J, Liu J, Huang Y, Zhong J-J, Tang W. Enhancement of IL-2 and IFN-γ expression and NK cells activity involved in the anti-tumor effect of ganoderic acid Me in vivo. Int Immunopharmacol. 2007;7(6):864–70.
80. Kim HW, Kim BK. Biomedicinal triterpenoids of Ganoderma lucidum (Curt.: Fr.) P. Karst.(Aphyllophoromycetideae). Int J Med Mushrooms. 1999;1(2).
81. Liu C, Song Y, Yang N, Tversky JR, Reid-Adam J, Li X-M. Ganoderic acid β suppressed Th2 responses and induced Th1/Tregs in cultures of peripheral blood mononuclear cells from asthmatic patients. J Allergy Clin Immunol. 2013;131(2):AB1-AB.
82. Agrawal DK, Shao Z. Pathogenesis of allergic airway inflammation. Curr Allergy Asthma Rep. 2010;10(1):39–48.
83. Wang CN, Chen JC, Shiao MS, Wang CT. The aggregation of human platelet induced by ganodermic acid S. BBA-Biomembranes. 1989;986(1):151–60.
84. Su CY, Shiao MS, Wang CT. Differential effects of ganodermic acid S on the thromboxane A signaling pathways in human platelets. Biochem Pharmacol. 1999;58(4):587–95.
85. Li CH, Chen PY, Chang UM, Kan LS, Fang WH, Tsai KS, et al. Ganoderic acid X, a lanostanoid triterpene, inhibits topoisomerases and induces apoptosis of cancer cells. Life Sci. 2005;77(3):252–65.
86. Yue QX, Cao ZW, Guan SH, Liu XH, Tao L, Wu WY, et al. Proteomics characterization of the cytotoxicity mechanism of ganoderic acid D and computer-automated estimation of the possible drug target network. Mol Cell Proteomics. 2008;7(5):949–61.
87. Harhaji Trajković LM, Mijatović SA, Maksimović-Ivanić DD, Stojanović ID, Momčilović MB, Tufegdžić SJ, et al. Anticancer properties of Ganoderma lucidum methanol extracts in vitro and in vivo. Nutr Cancer. 2009;61(5):696–707.
88. Wen T. The inhibition effect of triterpenoid in Ganoderma on topoisomerase I. J Shanghai Inst Technol. 2011;2:001.
89. Hossain A, Radwan FF, Doonan BP, God JM, Zhang L, Bell PD, et al. A possible cross-talk between autophagy and apoptosis in generating an immune response in melanoma. Apoptosis. 2012;17(10):1066–78.
90. Yoon SY, Eo SK, Kim YS, Lee CK, Han SS. Antimicrobial activity of Ganoderma lucidum extract alone and in combination with some antibiotics. Arch Pharmacal Res. 1994;17(6):438–42.
91. Keypour S, Riahi H, Moradali M-F, Rafati H. Investigation of the antibacterial activity of a chloroform extract of Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum (W. Curt.: Fr.) P. Karst.(Aphyllophoromycetideae), from Iran. Int J Med Mushrooms. 2008;10(4).
92. Johnson B, Doonan B, Radwan FF, Haque A. Ganoderic acid DM: an alternative agent for the treatment of advanced prostate cancer. Open Prost Cancer J. 2010;3:78–85.
93. Miyamoto I, Liu J, Shimizu K, Sato M, Kukita A, Kukita T, et al. Regulation of osteoclastogenesis by ganoderic acid DM isolated from Ganoderma lucidum. Eur J Pharmacol. 2009;602(1):1–7.
94. Mor A, Philips MR. Compartmentalized ras/mapk signaling. Annu Rev Immunol. 2006;24:771–800.
95. Morgensztern D, McLeod HL. PI3K/Akt/mTOR pathway as a target for cancer therapy. Anti-cancer drug. 2005;16(8):797–803.
96. Zoncu R, Efeyan A, Sabatini DM. mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol. 2011;12(1):21–35.
97. Vigneri P, Frasca F, Sciacca L, Pandini G, Vigneri R. Diabetes and cancer. Endoc Relat Cancer. 2009;16(4):1103–23.
98. Vermeulen K, Van Bockstaele DR, Berneman ZN. The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif. 2003;36(3):131–49.
99. Chang CJ, Chen YYM, Lu CC, Lin CS, Martel J, Tsai S-H, et al. Ganoderma lucidum stimulates NK cell cytotoxicity by inducing NKG2D/NCR activation and secretion of perforin and granulysin. J Innate Immun. 2013:1753425913491789.
100. Suarez Arroyo IJ, Rosario Acevedo R, Aguilar Perez A, Clemente PL, Cubano LA, Serrano J, et al. Anti-tumor effects of Ganoderma lucidum (Reishi) in inflammatory breast cancer in in vivo and in vitro models. PLoS One. 2013;8(2), e57431.
101. Haniadka R, Popouri S, Palatty PL, Arora R, Baliga MS. Medicinal plants as antiemetics in the treatment of cancer: a review. Integr Cancer Ther. 2012;11(1):18–28.
102. Bao P-P, Lu W, Cui Y, Zheng Y, Gu K, Chen Z, et al. Ginseng and Ganoderma lucidum use after breast cancer diagnosis and quality of life: a report from the Shanghai Breast Cancer Survival Study. PLoS One. 2012;7(6), e39343.
103. Santra S, Kaittanis C, Grimm J, Perez JM. Drug/dye-loaded, multifunctional iron oxide nanoparticles for combined targeted cancer therapy and dual optical/magnetic resonance imaging. Small. 2009;5(16):1862–8.
104. Low PS, Henne WA, Doorneweerd DD. Discovery and development of folic-acid-based receptor targeting for imaging and therapy of cancer and inflammatory diseases. Acc Chem Res. 2007;41(1):120–9.
105. Li N, Hu YL, He CX, Hu CJ, Zhou J, Tang GP, et al. Preparation, characterisation and anti-tumour activity of Ganoderma lucidum polysaccharide nanoparticles. J Pharm Pharmacol. 2010;62(1):139–44.
106. Kennedy EM, P’Pool SJ, Jiang J, Sliva D, Minto RE. Semisynthesis and biological evaluation of ganodermanontriol and its stereoisomeric triols. J Nat Prod. 2011;74(11):2332–7.
107. Jedinak A, Thyagarajan-Sahu A, Jiang J, Sliva D. Ganodermanontriol, a lanostanoid triterpene from Ganoderma lucidum, suppresses growth of colon cancer cells through ss-catenin signaling. Int J Oncol. 2011;38(3):761–7.
108. Liu J, Shimizu K, Kondo R. The effects of Ganoderma alcohols isolated from Ganoderma lucidum on the androgen receptor binding and the growth of LNCaP cells. Fitoterapia. 2010;81(8):1067–72.
109. Chang U-M, Li C-H, Lin L-I, Huang C-P, Kan L-S, Lin S-B. Ganoderiol F, a Ganoderma triterpene, induces senescence in hepatoma HepG2 cells. Life Sci. 2006;79(12):1129–39.
110. Liu J, Shimizu K, Konishi F, Kumamoto S, Kondo R. The anti-androgen effect of ganoderol B isolated from the fruiting body of Ganoderma lucidum. Bioorg Med Chem. 2007;15(14):4966–72.
111. Teng BS, Wang CD, Yang HJ, Wu JS, Zhang D, Zheng M, et al. A protein tyrosine phosphatase 1B activity inhibitor from the fruiting bodies of Ganoderma lucidum (Fr.) Karst and its hypoglycemic potency on streptozotocin-induced type 2 diabetic mice. J Agr Food Chem. 2011;59(12):6492–500.
112. Negi A, Pandey AK, Joshi G, Agnihotri V. Impact of protein tyrosine phosphate on cancer metastasis: an overview. World J Pharm Res Technol. 2013;1(2):118–30.
113. Cuong TD, Hung TM, Lee JH, Woo MH, Choi JS, Kim J, et al. Inhibitory effect on NO production of triterpenes from the fruiting bodies of Ganoderma lucidum. Bioorg Med Chem Lett. 2013;23(5):1428–32.
114. Babitskaya V, Shcherba V, Puchkova T, Smirnov D. Polysaccharides of Ganoderma lucidum: factors affecting their production. Appl Biochem Microbiol. 2005;41(2):169–73.
115. Sanodiya BS, Thakur GS, Baghel RK, Prasad G, Bisen P. Ganoderma lucidum: a potent pharmacological macrofungus. Curr Pharm Biotechnol. 2009;10(8):717–42.
116. Peng Y, Zhang L, Zeng F, Kennedy JF. Structure and antitumor activities of the water-soluble polysaccharides from Ganoderma tsugae mycelium. Carbohydr Polym. 2005;59(3):385–92.
117. Yang Q, Wang S, Xie Y, Sun J, Wang J. HPLC analysis of Ganoderma lucidum polysaccharides and its effect on antioxidant enzymes activity and Bax, Bcl-2 expression. Int J Biol Macromol. 2010;46(2):167–72.
118. Bao X-F, Wang X-S, Dong Q, Fang J-N, Li X-Y. Structural features of immunologically active polysaccharides from Ganoderma lucidum. Phytochemistry. 2002;59(2):175–81.
119. Hsu J-W, Huang H-C, Chen S-T, Wong C-H, Juan H-F. Ganoderma lucidum polysaccharides induce macrophage-like differentiation in human leukemia THP-1 cells via caspase and p53 activation. J Evid Based Complement Altern Med. 2011;2011.
120. Zhang Q, Lin Z. The antitumor activity of Ganoderma lucidum (Curt Fr) P Karst (Lingzhi) (Aphyllophoromycetideae) polysaccharides is related to tumor necrosis factor-α and interferon-γ. Int J Med Mushroom. 1999;1(1):207–15.
121. Liu W, Wang H, Pang X, Yao W, Gao X. Characterization and antioxidant activity of two low-molecular-weight polysaccharides purified from the fruiting bodies of Ganoderma lucidum. Int J Biol Macromol. 2010;46(4):451–7.
122. Gao Y, Zhou S, Jiang W, Huang M, Dai X. Effects of Ganopoly® (a Ganoderma lucidum polysaccharide extract) on the immune functions in advanced-stage cancer patients. Immunol Invest. 2003;32(3):201–15.
123. Sone Y, Okuda R, Wada N, Kishida E, Misaki A. Structures and antitumor activities of the polysaccharides isolated from fruiting body and the growing culture of mycelium of Ganoderma lucidum. Agric Biol Chem. 1985;9:2641–53.
124. Sun J, He H, Xie BJ. Novel antioxidant peptides from fermented mushroom Ganoderma lucidum. J Agr Food Chem. 2004;52(21):6646–52.
125. Jia J, Zhang X, Hu YS, Wu Y, Wang QZ, Li NN, et al. Evaluation of in vivo antioxidant activities of Ganoderma lucidum polysaccharides in STZ-diabetic rats. Food Chem. 2009;115(1):32–6.
126. Zhao L, Dong Y, Chen G, Hu Q. Extraction, purification, characterization and antitumor activity of polysaccharides from Ganoderma lucidum. Carbohydr Polym. 2010;80(3):783–9.
127. Chen Y, Xie MY, Nie SP, Li C, Wang YX. Purification, composition analysis and antioxidant activity of a polysaccharide from the fruiting bodies of Ganoderma atrum. Food Chem. 2008;107(1):231–41.
128. Lee JM, Kwon H, Jeong H, Lee JW, Lee SY, Baek SJ, et al. Inhibition of lipid peroxidation and oxidative DNA damage by Ganoderma lucidum. Phytother Res. 2001;15(3):245–9.
129. Yang B-K, Wilson MA, Cho K, Song C-H. Hypoglycemic effect of exo-and endo-biopolymers produced by submerged mycelial culture of Ganoderma lucidum in streptozotocin-induced diabetic rats. Appl Microbiol Biotechnol. 2004;14(5):972–7.
130. Gao Y, Lan J, Dai X, Ye J, Zhou S. A phase I/II study of Lingzhi mushroom Ganoderma lucidum (W. Curt.: Fr.) Lloyd (Aphyllophoromycetideae) extract in patients with type ii diabetes mellitus. Int J Med Mushrooms. 2004;6(1).
131. Hikino H, Konno C, Mirin Y, Hayashi T. Isolation and hypoglycemic activity of ganoderans A and B, glycans of Ganoderma lucidum fruit bodies. Planta Med. 1985;51(04):339–40.
132. Seto S, Lam T, Tam H, Au A, Chan S, Wu J, et al. Novel hypoglycemic effects of Ganoderma lucidum water-extract in obese/diabetic mice. Phytomedicine. 2009;16(5):426–36.
133. Meng G, Zhu H, Yang S, Wu F, Zheng H, Chen E, et al. Attenuating effects of Ganoderma lucidum polysaccharides on myocardial collagen cross-linking relates to advanced glycation end product and antioxidant enzymes in high-fat-diet and streptozotocin-induced diabetic rats. Carbohydr Polym. 2011;84(1):180–5.
134. He CY, Li WD, Guo SX, Lin SQ, Lin ZB. Effect of polysaccharides from Ganoderma lucidum on streptozotocin-induced diabetic nephropathy in mice. J Asian Nat Prod Res. 2006;8(8):705–11.
135. Zhang H-N, Lin Z-B. Hypoglycemic effect of Ganoderma lucidum polysaccharides. Acta Pharmacol Sin. 2004;25(2):191–5.
136. Li F, Zhang Y, Zhong Z. Antihyperglycemic effect of Ganoderma lucidum polysaccharides on streptozotocin-induced diabetic mice. Intl J Mol Sci. 2011;12(9):6135–45.
137. Lin CY, Chen YH, Lin CY, Hsu HY, Wang SH, Liang CJ, et al. Ganoderma lucidum polysaccharides attenuate endotoxin-induced intercellular cell adhesion molecule-1 expression in cultured smooth muscle cells and in the neointima in mice. J Agric Food Chem. 2010;58(17):9563–71.
138. Liu J, Yang F, Ye L-B, Yang X-J, Timani KA, Zheng Y, et al. Possible mode of action of antiherpetic activities of a proteoglycan isolated from the mycelia of Ganoderma lucidum in vitro. J Ethnopharmacol. 2004;95(2):265–72.
139. Kim YS, Eo SK, Oh KW, Lee CK, Han SS. Antiherpetic activities of acidic protein bound polysacchride isolated from Ganoderma lucidum alone and in combinations with interferons. J Ethnopharmacol. 2000;72(3):451–8.
140. Wang YY, Khoo KH, Chen ST, Lin CC, Wong CH, Lin CH. Studies on the immuno-modulating and antitumor activities of Ganoderma lucidum (Reishi) polysaccharides: functional and proteomic analyses of a fucose-containing glycoprotein fraction responsible for the activities. Bioorg Med Chem. 2002;10(4):1057–62.
141. Spackman D, Stein W, Moore S. Chromatography of amino acids on sulphonated polystyrene resins. An improved system. Anal Chem. 1958;30:1185–9.
142. Lin C-H, Hsiao Y-M, Ou C-C, Lin Y-W, Chiu Y-L, Lue K-H, et al. GMI, a Ganoderma immunomodulatory protein, down-regulates tumor necrosis factor α-induced expression of matrix metalloproteinase 9 via NF-κB pathway in human alveolar epithelial A549 cells. J Agri Food Chem. 2010;58(22):12014–21.
143. Kino K, Yamashita A, Yamaoka K, Watanabe J, Tanaka S, Ko K, et al. Isolation and characterization of a new immunomodulatory protein, ling zhi-8 (LZ-8), from Ganoderma lucidum. J Biol Chem. 1989;264(1):472–8.
144. Chuang CM, Wang HE, Chang CH, Peng CC, Ker YB, Lai JE, et al. Sacchachitin, a novel chitin-polysaccharide conjugate macromolecule present in Ganoderma lucidum: purification, composition, and properties. Pharm Biol. 2013;51(1):84–95.
145. Kohsuke K, Toshio S, Watanabe J, Yamashita A, Tsuboi H, Miyajima H, et al. Immunomodulator, LZ-8, prevents antibody production in mice. Int J Immunopharmacol. 1991;13(8):1109–15.
146. Hsu HY, Kuan YC, Lin TY, Tsao SM, Hsu J, Ma LJ, et al. Reishi protein LZ-8 induces FOXP3. J Evi Based Complement Altern Med. 2013;2013.
147. Wu CT, Lin TY, Hsu HY, Sheu F, Ho C-M, Chen EIT. Ling Zhi-8 mediates p53-dependent growth arrest of lung cancer cells proliferation via the ribosomal protein S7-MDM2-p53 pathway. Carcinogenesis. 2011;32(12):1890–6.
148. Liang C, Li H, Zhou H, Zhang S, Liu Z, Zhou Q, et al. Recombinant Lz-8 from Ganoderma lucidum induces endoplasmic reticulum stress-mediated autophagic cell death in SGC-7901 human gastric cancer cells. Oncol Rep. 2012;27(4):1079–89.
149. Ansor NM, Abdullah N, Aminudin N. Anti-angiotensin converting enzyme (ACE) proteins from mycelia of Ganoderma lucidum (Curtis) P. Karst. BMC Complement Altern Med. 2013;13(1):256.
150. Hsu C-C, Chen C-H, Hsu T-I, Hung J-J, Ko J-L, Zhang B, et al. The 58-kDa microspherule protein (MSP58) represses human telomerase reverse transcriptase (hTERT) gene expression and cell proliferation by interacting with telomerase transcriptional element-interacting factor (TEIF). Biochimica et Biophysica Acta (BBA)- Mol Cell Res. 2013;1843(3):565–79.
151. Liao CH, Hsiao YM, Hsu CP, Lin MY, Wang JCH, Huang YL, et al. Transcriptionally mediated inhibition of telomerase of fungal immunomodulatory protein from Ganoderma tsugae in A549 human lung adenocarcinoma cell line. Mol Carcinog. 2006;45(4):220–9.
152. Ngai PH, Ng T. A mushroom (Ganoderma capense) lectin with spectacular thermostability, potent mitogenic activity on splenocytes, and antiproliferative activity toward tumor cells. Biochem Biophys Res Commun. 2004;314(4):988–93.
153. Zhou S, Gao Y, Chan E. Clinical trials for medicinal mushrooms: experience with Ganoderma lucidum (W. Curt.: Fr.) Lloyd (Lingzhi mushroom). Int J Med Mushrooms. 2005;7(1&2).
154. Jin X, Ruiz Beguerie J, Sze DMy, Chan GC. Ganoderma lucidum (Reishi mushroom) for cancer treatment. Cochrane Libr. 2012.
155. Gao Y, Zhou S, Chen G, Dai X, Ye J, Gao H. A phase I/II study of a Ganoderma lucidum (Curt.: Fr.) P. Karst.(Lingzhi, Reishi Mushroom) extract in patients with chronic hepatitis В. Int J Med Mushrooms. 2002;4(4).
156. Wicks SM, Tong R, Wang C-Z, O’Connor M, Karrison T, Li S, et al. Safety and tolerability of Ganoderma lucidum in healthy subjects: a double-blind randomized placebo-controlled trial. Am J Chin Med. 2007;35(03):407–14.
157. Noguchi M, Kakuma T, Tomiyasu K, Yamada A, Itoh K, Konishi F, et al. Randomized clinical trial of an ethanol extract of Ganoderma lucidum in men with lower urinary tract symptoms. Asian J Androl. 2008;10(5):777–85.
158. Soo TS. Effective dosage of the extract of Ganoderma lucidum in the treatment of various ailments. Mushroom biology and mushroom products. Royse: The Pennsylvania State University; 1996. p. 177–85.
159. Wanmuang H, Leopairut J, Kositchaiwat C, Wananukul W, Bunyaratvej S. Fatal fulminant hepatitis associated with Ganoderma lucidum (Lingzhi) mushroom powder. J Med Assoc Thai. 2007;90(1):179.
160. Kawagishi H, Fukuhara F, Sazuka M, Kawashima A, Mitsubori T, Tomita T. 5′-Deoxy-5′-methylsulphinyladenosine, a platelet aggregation inhibitor from Ganoderma lucidum. Phytochemistry. 1993;32(2):239–41.