Preventive and Therapeutic Effect of Ganoderma (Lingzhi) on Diabetes

  • Qian Liu
  • Lu TieEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1182)


As extracts from Ganoderma lucidum (G. lucidum, Lingzhi) have been reported to be an alternative adjuvant treatment for diabetes, numerous of work have been carried out on it. Among the many biologically active constituents of Ganoderma, polysaccharides, proteoglycans, proteins, and triterpenoids have been shown to have hypoglycemic effects. Based on our research and other references, this article discusses the antidiabetic effect of Ganoderma mediated by protecting pancreas islet; inhibiting protein tyrosine phosphatase 1B, a promising therapeutic target of diabetes; decreasing lymphocyte infiltration; and increasing the antibody detection of insulin in diabetic mice. This review summarizes researches about the hypoglycemic action effects of polysaccharides, proteoglycans, proteins, and triterpenoids from Ganoderma as a guide for future research on diabetes and its complications. In addition, clinical studies with diabetic indexes are reviewed.


Ganoderma Lingzhi Polysaccharides Diabetes Complication 


  1. 1.
    Karaa A, Goldstein A (2015) The spectrum of clinical presentation, diagnosis, and management of mitochondrial forms of diabetes. Pediatr Diabetes 16(1):1–9PubMedCrossRefGoogle Scholar
  2. 2.
    Butalia S, Kaplan GG, Khokhar B, Rabi DM (2016) Environmental risk factors and type 1 diabetes: past, present, and future. Can J Diabetes 40(6):586–593PubMedCrossRefGoogle Scholar
  3. 3.
    Petzold A, Solimena M, Knoch KP (2015) Mechanisms of beta cell dysfunction associated with viral infection. Curr Diab Rep 15(10):73PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    Ripsin CM, Kang H, Urban RJ (2009) Management of blood glucose in type 2 diabetes mellitus. Am Fam Physician 79(1):29–36Google Scholar
  5. 5.
    Tao Z, Shi A, Zhao J (2015) Epidemiological perspectives of diabetes. Cell Biochem Biophys 73(1):181–185PubMedCrossRefGoogle Scholar
  6. 6.
    Riserus U, Willett WC, Hu FB (2009) Dietary fats and prevention of type 2 diabetes. Prog Lipid Res 48(1):44–51PubMedCrossRefGoogle Scholar
  7. 7.
    Sanabria-Martinez G, Garcia-Hermoso A, Poyatos-Leon R, Alvarez-Bueno C, Sanchez-Lopez M, Martinez-Vizcaino V (2015) Effectiveness of physical activity interventions on preventing gestational diabetes mellitus and excessive maternal weight gain: a meta-analysis. BJOG 122(9):1167–1174PubMedCrossRefGoogle Scholar
  8. 8.
    Cizmarikova M (2017) The efficacy and toxicity of using the Lingzhi or Reishi medicinal mushroom, G. lucidum (agaricomycetes), and its products in chemotherapy (review). Int J Med Mushrooms 19(10):861–877PubMedCrossRefGoogle Scholar
  9. 9.
    Ahmad MF (2018) G. lucidum: persuasive biologically active constituents and their health endorsement. Biomed Pharmacother 107:507–519PubMedCrossRefGoogle Scholar
  10. 10.
    Chen Y, Qiao J, Luo J, Wu F, Meng G, Chen H, Zheng H, Xu J (2011) Effects of G. lucidum polysaccharides on advanced glycation end products and receptor of aorta pectoralis in T2DM rats. Zhongguo Zhong Yao Za Zhi 36(5):624–627PubMedPubMedCentralGoogle Scholar
  11. 11.
    Yang Z, Wu F, He Y, Zhang Q, Zhang Y, Zhou G, Yang H, Zhou P (2018) A novel PTP1B inhibitor extracted from G. lucidum ameliorates insulin resistance by regulating IRS1-GLUT4 cascades in the insulin signaling pathway. Food Funct 9(1):397–406CrossRefGoogle Scholar
  12. 12.
    Fatmawati S, Shimizu K, Kondo R (2010) Ganoderic acid Df, a new triterpenoid with aldose reductase inhibitory activity from the fruiting body of G. lucidum. Fitoterapia 81(8):1033–1036PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Kino K, Mizumoto K, Sone T, Yamaji T, Watanabe J, Yamashita A, Yamaoka K, Shimizu K, Ko K, Tsunoo H (1990) An immunomodulating protein, Ling Zhi-8 (LZ-8) prevents insulitis in non-obese diabetic mice. Diabetologia 33(12):713–718PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Radenkovic M, Stojanovic M, Prostran M (2016) Experimental diabetes induced by alloxan and streptozotocin: the current state of the art. J Pharmacol Toxicol Methods 78:13–31PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Bach EE, Hi EMB, Martins AMC, Nascimento PAM, Wadt NSY (2018) Hypoglycemic and hypolipidemic effects of G lucidum in streptozotocin-induced diabetic rats. Medicines (Basel) 5(3):pii: E78CrossRefGoogle Scholar
  16. 16.
    Lin CC, Yu YL, Shih CC, Liu KJ, Ou KL, Hong LZ, Chen JD, Chu CL (2011) A novel adjuvant Ling Zhi-8 enhances the efficacy of DNA cancer vaccine by activating dendritic cells. Cancer Immunol Immunother 60(7):1019–1027PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    van der Hem LG, van der Vliet JA, Bocken CF, Kino K, Hoitsma AJ, Tax WJ (1995) Ling Zhi-8: studies of a new immunomodulating agent. Transplantation 60(5):438–443PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Zhang HN, He JH, Yuan L, Lin ZB (2003) In vitro and in vivo protective effect of G. lucidum polysaccharides on alloxan-induced pancreatic islets damage. Life Sci 73(18):2307–2319CrossRefGoogle Scholar
  19. 19.
    He CY, Li WD, Guo SX, Lin SQ, Lin ZB (2006) Effect of polysaccharides from G. lucidum on streptozotocin-induced diabetic nephropathy in mice. J Asian Nat Prod Res 8(8):705–711PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Li K, Yu M, Hu Y, Ren G, Zang T, Xu X, Qu J (2016) Three kinds of G. lucidum polysaccharides attenuate DDC-induced chronic pancreatitis in mice. Chem Biol Interact 247:30–38PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Peterszegi G, Robert AM, Robert L (2003) Protection by L-fucose and fucose-rich polysaccharides against ROS-produced cell death in presence of ascorbate. Biomed Pharmacother 57(3–4):130–133PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Li F, Zhang Y, Zhong Z (2011) Antihyperglycemic effect of G. lucidum polysaccharides on streptozotocin-induced diabetic mice. Int J Mol Sci 12(9):6135–6145PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Zheng J, Yang B, Yu Y, Chen Q, Huang T, Li D (2012) G. lucidum polysaccharides exert anti-hyperglycemic effect on streptozotocin-induced diabetic rats through affecting beta-cells. Comb Chem High Throughput Screen 15(7):542–550PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Temneanu OR, Trandafir LM, Purcarea MR (2016) Type 2 diabetes mellitus in children and adolescents: a relatively new clinical problem within pediatric practice. J Med Life 9(3):235–239PubMedPubMedCentralGoogle Scholar
  25. 25.
    Mazo VK, Sidorova YS, Zorin SN, Kochetkova AA (2016) Streptozotocin induced diabetes rat models. Vopr Pitan 85(4):14–21PubMedPubMedCentralGoogle Scholar
  26. 26.
    Wang B, Chandrasekera PC, Pippin JJ (2014) Leptin- and leptin receptor-deficient rodent models: relevance for human type 2 diabetes. Curr Diabetes Rev 10(2):131–145PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Xiao C, Wu QP, Cai W, Tan JB, Yang XB, Zhang JM (2012) Hypoglycemic effects of G. lucidum polysaccharides in type 2 diabetic mice. Arch Pharm Res 35(10):1793–1801PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Wang F, Zhou Z, Ren X, Wang Y, Yang R, Luo J, Strappe P (2015) Effect of G. lucidum spores intervention on glucose and lipid metabolism gene expression profiles in type 2 diabetic rats. Lipids Health Dis 14:49PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Xiao C, Wu Q, Zhang J, Xie Y, Cai W, Tan J (2017) Antidiabetic activity of G. lucidum polysaccharides F31 down-regulated hepatic glucose regulatory enzymes in diabetic mice. J Ethnopharmacol 196:47–57PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Yang Z, Chen C, Zhao J, Xu W, He Y, Yang H, Zhou P (2018) Hypoglycemic mechanism of a novel proteoglycan, extracted from G. lucidum, in hepatocytes. Eur J Pharmacol 820:77–85PubMedCrossRefGoogle Scholar
  31. 31.
    Teng BS, Wang CD, Zhang D, Wu JS, Pan D, Pan LF, Yang HJ, Zhou P (2012) Hypoglycemic effect and mechanism of a proteoglycan from G. lucidum on streptozotocin-induced type 2 diabetic rats. Eur Rev Med Pharmacol Sci 16(2):166–175PubMedGoogle Scholar
  32. 32.
    Wang CD, Teng BS, He YM, Wu JS, Pan D, Pan LF, Zhang D, Fan ZH, Yang HJ, Zhou P (2012) Effect of a novel proteoglycan PTP1B inhibitor from G. lucidum on the amelioration of hyperglycaemia and dyslipidaemia in db/db mice. Br J Nutr 108(11):2014–2025PubMedCrossRefGoogle Scholar
  33. 33.
    Pan D, Zhang D, Wu J, Chen C, Xu Z, Yang H, Zhou P (2013) Antidiabetic, antihyperlipidemic and antioxidant activities of a novel proteoglycan from G. lucidum fruiting bodies on db/db mice and the possible mechanism. PLoS One 8(7):e68332PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Thyagarajan-Sahu A, Lane B, Sliva D (2011) ReishiMax, mushroom based dietary supplement, inhibits adipocyte differentiation, stimulates glucose uptake and activates AMPK. BMC Complement Altern Med 11:74PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Heng LZ, Comyn O, Peto T, Tadros C, Ng E, Sivaprasad S, Hykin PG (2013) Diabetic retinopathy: pathogenesis, clinical grading, management and future developments. Diabet Med 30(6):640–650PubMedCrossRefGoogle Scholar
  36. 36.
    Papadopoulou-Marketou N, Paschou SA, Marketos N, Adamidi S, Adamidis S, Kanaka-Gantenbein C (2018) Diabetic nephropathy in type 1 diabetes. Minerva Med 109(3):218–228PubMedGoogle Scholar
  37. 37.
    Roman-Pintos LM, Villegas-Rivera G, Rodriguez-Carrizalez AD, Miranda-Diaz AG, Cardona-Munoz EG (2016) Diabetic polyneuropathy in type 2 diabetes mellitus: inflammation, oxidative stress, and mitochondrial function. J Diabetes Res 2016:3425617PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Okonkwo UA, DiPietro LA (2017) Diabetes and wound angiogenesis. Int J Mol Sci 18(7):pii: E1419CrossRefGoogle Scholar
  39. 39.
    Tesch GH (2017) Diabetic nephropathy – is this an immune disorder? Clin Sci (Lond) 131(16):2183–2199CrossRefGoogle Scholar
  40. 40.
    Hussain N, Adrian TE (2017) Diabetic neuropathy: update on pathophysiological mechanism and the possible involvement of glutamate pathways. Curr Diabetes Rev 13(5):488–497PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Emerging Risk Factors C, Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di Angelantonio E, Ingelsson E, Lawlor DA, Selvin E, Stampfer M, Stehouwer CD, Lewington S, Pennells L, Thompson A, Sattar N, White IR, Ray KK, Danesh J (2010) Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 375(9733):2215–2222CrossRefGoogle Scholar
  42. 42.
    Lim JZ, Ng NS, Thomas C (2017) Prevention and treatment of diabetic foot ulcers. J R Soc Med 110(3):104–109PubMedCrossRefGoogle Scholar
  43. 43.
    O’Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, de Lemos JA, Ettinger SM, Fang JC, Fesmire FM, Franklin BA, Granger CB, Krumholz HM, Linderbaum JA, Morrow DA, Newby LK, Ornato JP, Ou N, Radford MJ, Tamis-Holland JE, Tommaso CL, Tracy CM, Woo YJ, Zhao DX, Anderson JL, Jacobs AK, Halperin JL, Albert NM, Brindis RG, Creager MA, DeMets D, Guyton RA, Hochman JS, Kovacs RJ, Kushner FG, Ohman EM, Stevenson WG, Yancy CW, American College of Cardiology Foundation/American Heart Association Task Force on Practice G (2013) 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 127(4):e362–e425PubMedCrossRefGoogle Scholar
  44. 44.
    Zhu KX, Nie SP, Li C, Gong D, Xie MY (2014) Ganoderma atrum polysaccharide improves aortic relaxation in diabetic rats via PI3K/Akt pathway. Carbohydr Polym 103:520–527PubMedCrossRefGoogle Scholar
  45. 45.
    Tie L, Yang HQ, An Y, Liu SQ, Han J, Xu Y, Hu M, Li WD, Chen AF, Lin ZB, Li XJ (2012) G. lucidum polysaccharide accelerates refractory wound healing by inhibition of mitochondrial oxidative stress in type 1 diabetes. Cell Physiol Biochem 29(3–4):583–594PubMedCrossRefGoogle Scholar
  46. 46.
    Cheng PG, Phan CW, Sabaratnam V, Abdullah N, Abdulla MA, Kuppusamy UR (2013) Polysaccharides-rich extract of G. lucidum (M.A. Curtis:Fr.) P. Karst accelerates wound healing in streptozotocin-induced diabetic rats. Evid Based Complement Alternat Med 2013:671252PubMedPubMedCentralGoogle Scholar
  47. 47.
    Pan D, Zhang D, Wu J, Chen C, Xu Z, Yang H, Zhou P (2014) A novel proteoglycan from G. lucidum fruiting bodies protects kidney function and ameliorates diabetic nephropathy via its antioxidant activity in C57BL/6 db/db mice. Food Chem Toxicol 63:111–118PubMedCrossRefGoogle Scholar
  48. 48.
    Zhu KX, Nie SP, Tan LH, Li C, Gong DM, Xie MY (2016) A polysaccharide from Ganoderma atrum improves liver function in type 2 diabetic rats via antioxidant action and short-chain fatty acids excretion. J Agric Food Chem 64(9):1938–1944PubMedCrossRefGoogle Scholar
  49. 49.
    Li SH, Wu HX (2011) Clinical analysis of BoZhi Glycopeptide injection in treating diabetic foot. J Hainan Med Coll 17(10):1333–1334Google Scholar
  50. 50.
    Chu TT, Benzie IF, Lam CW, Fok BS, Lee KK, Tomlinson B (2012) Study of potential cardioprotective effects of G. lucidum (Lingzhi): results of a controlled human intervention trial. Br J Nutr 107(7):1017–1027PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Klupp NL, Kiat H, Bensoussan A, Steiner GZ, Chang DH (2016) A double-blind, randomised, placebo-controlled trial of G. lucidum for the treatment of cardiovascular risk factors of metabolic syndrome. Sci Rep 6:29540PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Fan CH, Tong L, Zhang D, Zheng M, Yuan SS, Zhang C, He Q (2018) Effect of G. lucidum granules on glucose metabolism in patients with type 2 diabetes mellitus and its mechanism of action on inflammatory factors. Hebei J Tradit Chin Med 40(2):214–217Google Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical SciencesPeking UniversityBeijingChina
  2. 2.Beijing Key Laboratory of Tumor Systems BiologyPeking UniversityBeijingChina

Personalised recommendations