Immunostimulatory and anticancer effect of Reishi and Coriol extracts at the level of clinical studies and their implementation in practice

Česká verze

Authors: Jana Neuwirthová; Pavla Urbánková; Pavel Smilek
Authors place of work: Klinika otorinolaryngologie a chirurgie hlavy a krku LF UK a FN sv. Anny v Brně
Published in the journal: Klin Onkol 2020; 33(6): 426-434
Category: Přehled

Summary

Background: Mushrooms Reishi and Coriolus have been used for centuries in Asian countries to treat various diseases, mainly respiratory tract infections or pulmonary diseases, and more recently also cancers. Polysaccharides and triterpenes, which are found in these mushrooms, are their main bioactive components. Preclinical and clinical studies in humans presented their beneficial effects as immunomodulators; besides this, they possess a direct anticancer effect. In Asia, they are used after cancer treatment as single agents or in combination with chemotherapy or radiotherapy. Extracts from Coriolus have been approved for more than 30 years as an effective adjuvant addition to standard cancer treatment in Japan and China without obvious toxicity. Purpose: In this review, clinical studies with Reishi and Coriolus in cancer patients and their meta-analyses are briefly summarized. Conclusion: Both extracts from Reishi and Coriolus, if used in combination with standard therapy or as an adjuvant single agent, have shown benefits at immune function measures, tumor-related symptoms and performance status of cancer patients. Moreover, they have prolonged their disease-free interval and overall survival. They are well tolerated even in advanced cancer diseases and could be safely used continuously for long periods of time. Because of clinically approved efficacy and safety, they are applied mainly in some countries as a complementary therapy for various types of cancers.

Keywords:

Reishi – Ganoderma lucidum – polysaccharides – Coriolus – polysaccharide K – PSK – polysaccharide peptide – PSP – immunostimulation

Zdroje

1. Zhong L, Yan P, Lam WC et al. Coriolus versicolor and Ganoderma lucidum related natural products as an adjunct therapy for cancers: a systematic review and meta--analysis of randomized controlled trials. Front Pharmacol 2019; 13 (10): 703. doi: 10.3389/fphar.2019.00703.

2. Gao YH, Sai XH, Chen GL et al. A randomized, placebo--controlled, multi-center study of Ganoderma lucidum (W. Curt.: Fr.) Lloyd (Aphyllophoromycetideae) polysaccharides (Ganopoly) in patients with advanced lung cancer. Int J Med Mushrooms 2003; 5: 368–581. doi: 10.1615/InterJMedicMush.v5.i4.40.

3. Chiu HF, Fu HY, Lu YY et al. Triterpenoids and polysaccharide peptides-enriched Ganoderma lucidum: a randomized, double-blind placebo-controlled crossover study of its antioxidation and hepatoprotective efficacy in healthy volunteers. Pharm Biol 2017; 55 (1): 1041–1046. doi: 10.1080/13880209.2017.1288750.

4. Shing MK, Leung TF, Chu YL et al. Randomized, double--blind and placebo-controlled study of the immunomodulatory effects of Lingzhi in children with cancers. [online]. Available from: https: //ascopubs.org/doi/abs/10.1200/jco.2008.26.15_suppl.14021.

5. Henao SLD, Urrego SA, Cano AM et al. Randomized clinical trial for the evaluation of immune modulation by yogurt enriched with b-glucans from Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum (Agaricomycetes), in children from Medellin, Colombia. Int J Med Mushrooms 2018; 20 (8): 705–716. doi: 10.1615/IntJMedMushrooms.2018026986.

6. Avtonomova AV, Krasnopolskaya LM. Antiviral properties of basidiomycetes metabolites. Antibiot Khimioter 2014; 59 (7–8): 41–48.

7. Zhu Q, Bang TH, Ohnuki K et al. Inhibition of neuraminidase by Ganoderma triterpenoids and implications for neuraminidase inhibitor design. Sci Rep 2015; 5: 13194. doi: 10.1038/srep13194.

8. Zheng DS, Chen LS. Triterpenoids from Ganoderma lucidum inhibit the activation of EBV antigens as telomerase inhibitors. Exp Ther Med 2017; 14 (4): 3273–3278. doi: 10.3892/etm.2017.4883.

9. Huh S, Lee S, Choi SJ et al. Quercetin synergistically inhibit EBV-associated gastric carcinoma with Ganoderma lucidum extracts. Molecules 2019; 24 (21): 3834. doi: 10.3390/molecules24213834.

10. Niedermeyer TH, Lindequist U, Mentel R et al. Antiviral terpenoid constituents of Ganoderma pfeifferi. J Nat Prod. 2005; 68 (12): 1728–1731. doi: 10.1021/np0501886.

11. Hijikata Y, Yamada S, Yasuhara A. Herbal mixtures containing the mushroom Ganoderma lucidum improve recovery time in patients with herpes genitalis and labialis. J Altern Complement Med 2007; 13 (9): 985–987. doi: 10.1089/acm.2006.6297.

12. Donatini B. Control of oral human papillomavirus (HPV) by medicinal mushrooms, Trametes versicolor and Ganoderma lucidum: a preliminary clinical trial. Int J Med Mushrooms 2014; 16 (5): 497–498. doi: 10.1615/intjmedmushrooms.v16.i5.80.

13. Sohretoglu D, Huang S. Ganoderma lucidum Polysaccharides as An Anti-cancer Agent. Anticancer Agents Med Chem 2018; 18 (5): 667–674. doi: 10.2174/1871520617666171113121246.

14. Wachtel-Galor S, Yuen J, Buswell JA et al. Ganoderma lucidum (Lingzhi or Reishi): A medicinal mushroom. In: Benzie IFF, Wachtel-Galor S (eds.). Herbal Medicine: Biomolecular and Clinical Aspects. 2nd edition. Boca Raton (FL): CRC Press/Taylor & Francis 2011; Chapter 9.

15. Wu GS, Guo JJ, Bao JL. Anticancer properties of triterpenoids isolated from Ganoderma lucidum – a review. Expert Opin Investig Drugs 2013; 22 (8): 981–992. doi: 10.1517/13543784.2013.805202.

16. Neil JR, Smith JE, Sullivan R. Immunomodulatory activities of mushroom glucans and polysaccharide-protein complexes in animals and humans (a review). Int J Med Mushrooms 2003; 5: 95–110. doi: 10.1615/InterJMedicMush.v5.i2.10.

17. Liang C, Tian D, Liu Y et al. Review of the molecular mechanisms of Ganoderma lucidum triterpenoids: Ganoderic acids A, C2, D, F, DM, X and Y. Eur J Med Chem 2019; 174: 130–141. doi: 10.1016/j.ejmech.2019.04.039.

18. Gao JJ, Min BS, Ahn EM et al. New triterpene aldehydes, lucialdehydes A-C, from Ganoderma lucidum and their cytotoxicity against murine and human tumor cells. Chem Pharm Bull 2002; 50 (6): 837–840. doi: 10.1248/cpb.50.837.

19. Sun Y, Sun L. Cellular and molecular mechanism of Ganoderma (Lingzhi) against tumor. Adv Exp Med Biol 2019; 1182: 79–118. doi: 10.1007/978-981-32-9421-9_3.

20. Sohretoglu D, Huang S. Ganoderma lucidum polysaccharides as an anti-cancer agent. Anticancer Agents Med Chem 2018; 18 (5): 667–674. doi: 10.2174/1871520617666171113121246.

21. Wang YY, Khoo KH, Chen ST et al. Studies on the immuno-modulating and antitumor activities of Ganoderma lucidum (reishi) polysaccharides: functional and proteomic analyses of fucose-containing glycoprotein fraction responsible for the activities. Bioorg Med Chem 2002; 10 (4): 1057–1062. doi: 10.1016/s0968-0896 (01) 00377-7.

22. Chang YH, Yang JS, Yang JL et al. Gandoderma lucidum extract promotes immune responses in normal BALB/c mice in vivo. In Vivo 2009; 23 (5): 755–759.

23. Wang PY, Zhu XL, Lin ZB. Antitumor and immunomodulatory effects of polysaccharides from broken-spore of Ganoderma lucidum. Front Pharmacol 2012; 3: 135. doi: 10.3389/fphar.2012.00135.

24. Zhang J, Tang Q, Zimmerman-Kordmann M et al. Activation of B lymphocytes by GLIS, a bioactive proteoglycan from Ganoderma lucidum. Life Sci 2002; 71 (6): 623–638. doi: 10.1016/s0024-3205 (02) 01690-9.

25. Kladar NV, Gavarić NS, Božin BN. Ganoderma: insights into anticancer effects. Eur J Cancer Prev 2016; 25 (5): 462–471. doi: 10.1097/CEJ.0000000000000204.

26. Joseph S, Sabulal B, George V et al. Antitumor and anti-inflammatory activities of polysaccharides isolated from Ganoderma lucidum. Acta Pharm 2011; 61 (3): 335–342. doi: 10.2478/v10007-011-0030-6.

27. Šťastný M, Říhová B. Únikové strategie nádorů pozornosti imunitního systému. Klin Onkol 2015; 28 (Suppl 4): 28–37. doi: 10.14735/amko20154s28.

28. Hatina J. Imunologie nádorů – současný stav a poznatky z 1. mezinárodní konference základní a klinické imunogenomiky. Část I – Interakce nádoru a imunitního systému. Klin Onkol 2005; 18 (4): 119–125.

29. Eckschlager T, Radvanská J, Hladíková M et al. Poruchy imunity jako pozdní následky protinádorové léčby u dětí. In: 2007 XXXI. Brněnské onkologické dny a XXI. Konference pro sestry a laboranty, Dětská onkologie. Sborník abstrakt: 82.

30. Gao YH, Zhou SF, Jiang W et al. Effects of Ganopoly (a Ganoderma lucidum polysaccharide extract) on immune functions in advanced-stage cancer patients. Immunol Invest 2003; 32 (3): 201–215. doi: 10.1081/imm-120022979.

31. Jin X; Ruiz Beguerie J; Sze DM et al. Ganoderma lucidum (Reishi mushroom) for cancer treatment. Cochrane Database Syst Rev 2016; 4 (4): CD007731. doi: 10.1002/14651858.CD007731.pub3.

32. Sun LX, Li WD, Lin ZB et al. Protection against lung cancer patient plasma-induced lymphocyte suppression by Ganoderma lucidum polysaccharides. Cell Physiol Biochem 2014; 33 (2): 289–299. doi: 10.1159/000356669.

33. Oka S, Tanaka S, Yoshida S et al. A water-soluble extract from culture medium of Ganoderma lucidum mycelia suppresses the development of colorectal adenomas. Hiroshima J Med Sci 2010; 59 (1): 1–6.

34. Suprasert P, Apichartpiyakul C, Sakonwasun C et al. Clinical characteristics of gynecologic cancer patients who respond to salvage treatment with Lingzhi. Asian Pac J Cancer Prev 2014; 15 (10): 4193–4196. doi: 10.7314/apjcp.2014.15.10.4193.

35. Zhao H, Zhang Q, Zhao L et al. Spore powder of Ganoderma lucidum improves cancer-related fatigue in breast cancer patients undergoing endocrine therapy: a pilot clinical trial. Evid Based Complement Alternat Med 2012; 2012: 809614. doi: 10.1155/2012/809614.

36. Collado Mateo D, Pazzi F, Domínguez Muñoz FJ et al. Ganoderma lucidum improves physical fitness in woman with fibromyalgia. Nutr Hosp 2015; 32 (5): 2126–2135. doi: 10.3305/nh.2015.32.5.9601.

37. Zhang J, Gao X, Pan Y et al. Toxicology and immunology of Ganoderma lucidum polysaccharides in Kunming mice and Wistar rats. Int J Biol Macromol 2016; 85: 302–310. doi: 10.1016/j.ijbiomac.2015.

38. Dou H, Chang Y, Zhang L. Coriolus versicolor polysaccharopeptide as an immunotherapeutic in China. Prog Mol Biol Transl Sci 2019; 163: 361–381. doi: 10.1016/bs.pmbts.2019.03.001.

39. PDQ Integrative, Alternative, and Complementary Therapies Editorial Board. Medicinal Mushrooms (PDQ^®): Health Professional Version. 2019 Oct 25. In: PDQ Cancer Information Summaries. [online]. Available from: https: //pubmed.ncbi.nlm.nih.gov/27929633/.

40. Maehara Y, Tsujitani S, Saeki H et al. Biological mechanism and clinical effect of protein-bound polysaccharide K (KRESTIN (^®)): review of development and future perspectives. Surg Today 2012; 42 (1): 8–28. doi: 10.1007/s00595-011-0075-7.

41. Ng TB. A review of research on the protein-bound polysaccharide (polysaccharopeptide, PSP) from the mushroom Coriolus versicolor (Basidiomycetes: Polyporaceae). Gen Pharmacol 1998; 30 (1): 1–4. doi: 10.1016/s0306-3623 (97) 00076-1.

42. Kono K, Kawaguchi Y, Mizukami Y et al. Protein-bound polysaccharide K partially prevents apoptosis of circulating T cells induced by anti-cancer drug S-1 in patients with gastric cancer. Oncology 2008; 74 (3–4): 143–149. doi: 10.1159/000151361.

43. Akagi J, Baba H. PSK may suppress CD57+ T cells to improve survival of advanced gastric cancer patients. Int J Clin Oncol 2010; 15 (2): 145–152. PSK may suppress CD57+ T cells to improve survival of advanced gastric cancer patients.

44. Nakazato H, Koike A, Saji S et al. Efficacy of immunochemotherapy as adjuvant treatment after curative resection of gastric cancer. Study Group of Immunochemotherapy with PSK for Gastric Cancer. Lancet 1994; 343 (8906): 1122–1126. doi: 10.1016/s0140-6736 (94) 90233-x.

45. Toge T, Yamaguchi Y. Protein-bound polysaccharide increases survival in resected gastric cancer cases stratified with a preoperative granulocyte and lymphocyte count. Oncol Rep 2000; 7 (5): 1157–1161. doi: 10.3892/or.7.5.1157.

46. Oba K, Teramukai S, Kobayashi M et al. Efficacy of adjuvant immunochemotherapy with polysaccharide K for patients with curative resections of gastric cancer. Cancer Immunol Immunother 2007; 56 (6): 905–911. doi: 10.1007/s00262-006-0248-1.

47. Yoshitani S, Takashima S. Efficacy of postoperative UFT (Tegafur/Uracil) plus PSK therapies in elderly patients with resected colorectal cancer. Cancer Biother Radiopharm 2009; 24 (1): 35–40. doi: 10.1089/cbr.2008.0547.

48. Sakai T, Yamashita Y, Maekawa T et al. Immunochemotherapy with PSK and fluoropyrimidines improves long--term prognosis for curatively resected colorectal cancer. Cancer Biother Radiopharm 2008; 23 (4): 461–467. doi: 10.1089/cbr.2008.0484.

49. Sakamoto J, Morita S, Oba K et al. Meta-analysis group of the Japanese society for cancer of the colon rectum. Efficacy of adjuvant immunochemotherapy with polysaccharide K for patients with curatively resected colorectal cancer: a meta-analysis of centrally randomized controlled clinical trials. Cancer Immunol Immunother 2006; 55 (4): 404–411. doi: 10.1007/s00262-005-0054-1.

50. Sadahiro S, Suzuki T, Maeda Y et al. Effects of preoperative immunochemoradiotherapy and chemoradiotherapy on immune responses in patients with rectal adenocarcinoma. Anticancer Res 2010; 30 (3): 993–999.

51. Torkelson CJ, Sweet E, Martzen MR et al. Phase 1 clinical trial of Trametes versicolor in women with breast cancer. ISRN Oncol 2012; 2012: 251632. doi: 10.5402/2012/251632.

52. Go P, Chung CH. Adjuvant PSK immunotherapy in patients with carcinoma of the nasopharynx. J Int Med Res 1989; 17: 141–149. doi: 10.1177/030006058901700205.

53. Ogoshi K, Satou H, Isono K et al. Immunotherapy for esophageal cancer. A randomized trial in combination with radiotherapy and radiochemotherapy. Am J Clin Oncol 1995; 18 (3): 216–222.

54. Matsumoto K, Nakagami Y, Kishimoto T. The prevention of recurrence of superficical bladder tumours with immunochemotherapy. In: deKernion JB (ed.). International society of urology reports. Immunotherapy of urological tumours. Edinburgh: Churchill Livingstone 1990: 149–155.

55. Iino Y, Yokoe T, Maemura M et al. Immunochemotherapies versus chemotherapy as adjuvant treatment after curative resection of operable breast cancer. Anticancer Res 1995; 15 (6B): 2907–2911.

56. Fritz H, Kennedy DA, Ishii M et al. Polysaccharide K and Coriolus versicolor extracts for lung cancer: a systematic review. Integr Cancer Ther 2015; 14 (3): 201–211. doi: 10.1177/1534735415572883.

57. Motai H. PSK effectiveness for cancer pain relief: clinical study covering the last 11 years. Biotherapy 1992; 6: 950–956.