Cultivation, Bioactive Metabolites, and Application of Caterpillar Mushroom Cordyceps militaris: Current State, Issues, and Perspectives

  • Chapter
  • First Online:
Fungi and Fungal Products in Human Welfare and Biotechnology
  • 703 Accesses

Abstract

Cordyceps militaris is a valuable mushroom with wide use in food and medicine. This fungal product usage in many countries, especially in Southeast Asia, has become widespread. There is a growing realization that C. militaris can be used as a succedaneum for Chinese cordyceps (Ophiocordyceps sinensis) due to their similar chemical characteristics and therapeutic properties. In nature, the complicated life cycle of C. militaris consists of teleomorph stage, anamorph stage, and the lifespan of the host insects. The fruiting bodies propagated by inoculation on cereal substrates and silkworm pupae have been successfully mass-produced. A battery of active components such as cordycepin, adenosine, N6-(2-hydroxyethyl)-adenosine, carotenoid, and polysaccharide have been extracted from fruiting body. Evidence shows that C. militaris has various bioactivities such as immunomodulatory, anti-inflammatory, antitumor, antimicrobial, insecticidal, anti-fibrotic, liver protection, kidney protection, and pneumonia protection. This fungus finds can be found in functional food, healthcare fields, as well as skin care products in East Asian countries represented by China, Japan, and Korea. Full elucidation of the production capacities of different metabolites and the quality control of the products are critically needed in the future. This review will be helpful for the future research and application of this fungus.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (Canada)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (Canada)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (Canada)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (Canada)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Sung G, Hywel-Jones NL, Sung JM, Luangsa-ard JJ, Shrestha B et al (2007) Phylogenetic classification of Cordyceps and the Clavicipitaceous fungi. Stud Mycol 57:5–59

    Article  PubMed  PubMed Central  Google Scholar 

  2. Dong JZ, Lei C, Ai XR, Wang Y (2012) Selenium enrichment on Cordyceps militaris link and analysis on its main active components. Appl Biochem Biotechnol 166:1215–1224

    Article  CAS  PubMed  Google Scholar 

  3. Gao SY, Wang FZ (2008) Research of commercialized cultivation technology on cordyceps militaris. North Hortic 9:212–215. (in Chinese)

    Google Scholar 

  4. Yue GGL, Lau CBS, Fung KP, Leung PC, Ko WH (2008) Effects of Cordyceps sinensis, Cordyceps militaris and their isolated compounds on ion transport in Calu-3 human airway epithelial cells. J Ethnopharmacol 117:92–101

    Article  CAS  PubMed  Google Scholar 

  5. Jeong MH, Park YS, Jeong DH, Lee CG, Kim JS et al (2014) In vitro evaluation of Cordyceps militaris as a potential radioprotective agent. Int J Mol Med 34:1349–1357

    Article  PubMed  Google Scholar 

  6. Lee HH, Park H, Sung GH, Lee K, Lee T et al (2014) Anti-influenza effect of Cordyceps militaris through immunomodulation in a DBA/2 mouse model. Mikrobiol Zh 52:696–701

    Google Scholar 

  7. Liu F, Zhu ZY, Sun XL, Gao H, Zhang YM (2017a) The preparation of three selenium-containing Cordyceps militaris polysaccharides: characterization and anti-tumor activities. Int J Biol Macromol 99:196–204

    Article  CAS  PubMed  Google Scholar 

  8. Dai JJ, Fan T, Wu CH, **ao LZ, Tian SF (2007) Summarization of the study on the artificial cultivation of Cordyceps militaris link. J Anhui Agric Sci 35:5469–5471. (in Chinese)

    Google Scholar 

  9. Gu YX, Wang ZS, Li SX, Yuan QS (2007) Effect of multiple factors on accumulation of nucleosides and bases in Cordyceps militaris. Food Chem 102:1304–1309

    Article  CAS  Google Scholar 

  10. Lu YZ, **a YL, Luo FF, Dong CH, Wang CS (2016) Functional convergence and divergence of mating-type genes fulfilling in Cordyceps militaris. Fungal Genet Biol 2016(88):35–43

    Article  Google Scholar 

  11. **ong CH, **a YL, Zheng P, Wang CS (2013) Increasing oxidative stress tolerance and subculturing stability of cordyceps militaris by overexpression of a glutathione peroxidase gene. Appl Microbiol Biotechnol 97:2009–2015

    Article  CAS  PubMed  Google Scholar 

  12. Yin J, **n XD, Weng YJ, Gui ZZ (2017) Transcriptome-wide analysis reveals the progress of cordyceps militaris subculture degeneration. PLoS One 12:e0186279

    Article  PubMed  PubMed Central  Google Scholar 

  13. Lou HW, Lin JF, Guo LQ, Wang XW, Tian SQ et al (2019) Advances in research on Cordyceps militaris degeneration. Appl Microbiol Biotechnol 103:7835–7841

    Article  CAS  PubMed  Google Scholar 

  14. Liu Q, Wang F, Liu KB, Dong CH (2018) Influence of strain preservation methods on fruiting body growth and metabolite production by the medicinal mushroom Cordyceps militaris (ascomycetes). Int J Med Mushrooms 20:1003–1011

    Article  PubMed  Google Scholar 

  15. Ahn YJ, Park SJ, Lee SG, Shin SC, Choi DH (2000) Cordycepin: selective growth inhibitor derived from liquid culture of Cordyceps militaris against Clostridium spp. J Agric Food Chem 48:2744–2748

    Article  CAS  PubMed  Google Scholar 

  16. Cunningham KG, Manson W, Spring FS, Hutchinson SA (1950) Cordycepin, a metabolic product isolated from cultures of Cordyceps militaris (Linn.) link. Nature 166:949–949

    Article  CAS  PubMed  Google Scholar 

  17. Kredich NM, Guarino AJ (1961) Homocitrullylaminoadenosine, a nucleoside isolated form Cordyceps militaris. J Biol Chem 236:3300–3302

    Article  CAS  PubMed  Google Scholar 

  18. Lennon MB, Suhadolnik RJ (1976) Biosynthesis of 3'-Deoxydenosine by cordyceps-militaris-mechanism of reduction. Biochim Biophys Acta-Biomembr 425:532–536

    Article  CAS  Google Scholar 

  19. **a YL, Luo FF, Shang YF, Chen PL, Lu YZ, Wang CS (2017) Fungal cordycepin biosynthesis is coupled with the production of the safeguard molecule pentostatin. Cell Chem Biol 24:1479–1489

    Article  CAS  PubMed  Google Scholar 

  20. Shao LW, Huang LH, Yan S, ** JD, Ren SY (2016) Cordycepin induces apoptosis in human liver cancer HepG2 cells through extrinsic and intrinsic signaling pathways. Oncol Lett 12:995–1000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Tian T, Song L, Zheng Q, Hu XJ, Yu RM (2014) Induction of apoptosis by Cordyceps militaris fraction in human chronic myeloid leukemia K562 cells involved with mitochondrial dysfunction. Pharmacogn Mag 10:325–331

    Article  PubMed  PubMed Central  Google Scholar 

  22. Tao XD, Ning Y, Zhao XW, Pan T (2016) The effects of cordycepin on the cell proliferation, migration and apoptosis in human lung cancer cell lines A549 and NCI-H460. J Pharm Pharmacol 68:901–911

    Article  CAS  PubMed  Google Scholar 

  23. Wang J, Chen C, Jiang ZH, Wang M, Jiang H, Zhang XY (2016) Protective effect of Cordyceps militaris extract against bisphenol an induced reproductive damage. Syst Biol Reprod Med 62:249–257

    Article  CAS  PubMed  Google Scholar 

  24. Robinson DR, Wu YM, Lonigro RJ, Vats P, Cobain E et al (2017) Integrative clinical genomics of metastatic cancer. Nature 548:297–303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Baik JS, Mun SW, Kim KS, Park SJ, Yoon HK et al (2016) Apoptotic effects of Cordycepin through the extrinsic pathway and p38 MAPK activation in human glioblastoma U87MG cells. J Microbiol Biotechnol 26:309–314

    Article  CAS  PubMed  Google Scholar 

  26. Hwang JH, Joo JC, Kim DJ, Jo E, Jang IS (2016) Cordycepin promotes apoptosis by modulating the ERK-JNK signaling pathway via DUSP5 in renal cancer cells. Am J Cancer Res 6:1758–1771

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Fishman P, Bar-Yehuda S, Liang BT, Jacobson KA (2012) Pharmacological and therapeutic effects of A3 adenosine receptor agonists. Drug Discov 17:359–366

    CAS  Google Scholar 

  28. Zhong L, Zhao L, Yang F, Yang W, Sun Y et al (2017) Evaluation of anti-fatigue property of the extruded product of cereal grains mixed with Cordyceps militaris on mice. J Int Soc Sport Nutr 14:15

    Article  Google Scholar 

  29. Yao LH, Huang JN, Li CH, Li HH, Yan WW et al (2013) Cordycepin suppresses excitatory synaptic transmission in rat hippocampal slices via a presynaptic mechanism. CNS Neurosci Ther 19:216–221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Jiang X, Tang PC, Chen Q, Zhang X, Fan YY et al (2019) Cordycepin exerts neuroprotective effects via an anti-apoptotic mechanism based on the mitochondrial pathway in a rotenone-induced parkinsonism rat model. CNS Neurol Disord Drug Targets 18:609–620

    Article  CAS  PubMed  Google Scholar 

  31. Devi A, Chennakesavulu S, Suresh C, Reddy ABM (2018) In: Rani V, Yadav UCS (eds) Nutraceuticals and their role in human health and disease. Functional food and human health. Springer Nature, Singapore, pp 375–403

    Chapter  Google Scholar 

  32. Woo PWK, Dion HW, Lange SM, Dahl LF & Durham LJ (1975) Cheminform abstract: a novel adenosine and Ara-A, deaminase inhibitor, (R)-3-(2-deoxy-beta-D-erythropento-furanosyl)-3, 6, 7, 8-tetrahydroimidazo (4, 5-D) (1, 3) diazepin-8-OL. Chem. Inform. 6: Abstract 446

    Google Scholar 

  33. Lamanna N, Kay NE (2009) Pentostatin treatment combinations in chronic lymphocytic leukemia. Clin Adv Hematol Oncol 7:386–392

    PubMed  Google Scholar 

  34. Bolanos MJ, Jacobsohn DA, Margolis J, Ogden A, Wientjes MG et al (2005) Pentostatin in steroid-refractory acute graft-versus-host disease. J Clin Oncol 23:2661–2668

    Article  Google Scholar 

  35. Jacobsohn DA, Chen AR, Zahurak M, Piantadosi S, Anders V, Bolanos MJ (2007) Phase II study of Pentostatin in patients with corticosteroid-refractory chronic graft-versus-host disease. J Clin Oncol 25:4255–4261

    Article  CAS  PubMed  Google Scholar 

  36. Parmar S, Andersson BS, Couriel D, Munsell MF, Fernandez-Vina M et al (2011) Prophylaxis of graft-versus-host disease in unrelated donor transplantation with pentostatin, tacrolimus, and mini-methotrexate: a phase I/II controlled, adaptively randomized study. J Clin Oncol 29:294–302

    Article  CAS  PubMed  Google Scholar 

  37. do Carmo GM, de Sa Ma F, Grando TH, Gressler LT, Baldissera MD et al (2019) Cordycepin (3′-deoxyadenosine) and pentostatin (deoxycoformycin) against Trypanosoma cruzi. Exp Parasitol 199:47–51

    Article  PubMed  Google Scholar 

  38. Jacobson KA, Hoffmann C, Cattabeni F, Abbracchio MP (1999) Adenosine-induced cell death: evidence for receptor-mediated signalling. Apoptosis 4:197–211

    Article  CAS  PubMed  Google Scholar 

  39. Novotný J (2015) Adenosine and its role in physiology. Cesk Fysiol 64:35–44

    PubMed  Google Scholar 

  40. Choudhury H, Chellappan DK, Sengupta P, Pandey M, Gorain B (2019) Adenosine receptors in modulation of central nervous system disorders. Curr Pharm Des 25:2808–2827

    Article  CAS  PubMed  Google Scholar 

  41. Nattel S (2012) Adenosine and atrial arrhythmias: exploring electrophysiological mechanisms in vivo. PACE-Pacing Clin Electrophysiol 35:553–555

    Article  PubMed  Google Scholar 

  42. Lindquist BE, Shuttleworth CW (2017) Evidence that adenosine contributes to Leao's spreading depression in vivo. J Cereb Blood Flow Metab 37:1656–1669

    Article  CAS  PubMed  Google Scholar 

  43. Leone RD, Emens LA (2018) Targeting adenosine for cancer immunotherapy. J Immunother Cancer 6:57

    Article  PubMed  PubMed Central  Google Scholar 

  44. Mcpartland J, Volkmar FR (2012) Autism and related disorders. Handb Clin Neurol 106:407

    Article  PubMed  Google Scholar 

  45. Masino SA, Kawamura M Jr, Cote JL, Williams RB, Ruskin DN (2013) Adenosine and autism: a spectrum of opportunities. Neuropharmacology 68:116–121

    Article  CAS  PubMed  Google Scholar 

  46. Furuya T, Hirotani M, Matsuzawa M (1983) N6-(2-hydroxyethyl) adenosine, a biologically active compound from cultured mycelia of Cordyceps and Isaria species. Phytochemistry 22:2509–2512

    Article  CAS  Google Scholar 

  47. Liu K, Wang F, Wang WZ, Dong CH (2017b) Beauveria bassiana: a new N6-(2-hydroxyethyl)-adenosine-producing fungus. Mycology 8:259–266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Wang DM, Liu XH, Guo H, Huang JH, Wang L (2013) Design, synthesis and biological activity evaluation of adenosine analogues. Acta Pharm Sin 48:881–886. (in Chinese)

    CAS  Google Scholar 

  49. Zhu LN, Xue JJ, Liu YF, Zhou S, Tang QJ (2013) Isolation, purification and anti-tumor activity of N6-(2-hydroxyethyl)-adenosine from the fruiting body Cordyceps militaris cultured. Acta Edulis Fungi 20:62–65. (in Chinese)

    Google Scholar 

  50. Chai YQ, Wei ZM, Chen ZA, Li XL, Liu YG et al., (2004) N6-(2-hydroxyethyl)-adenosine’ application in the preparation of analgesic drugs. China, ZL200410094511.0 (in Chinese)

    Google Scholar 

  51. Peng XX, Chai YQ, Zhu BC, ** YW, Li XL et al (2015) The protective effects of N~6-(2-hydroxyethyl)-adenosine extracted from Ophiocordyceps sobolifera on renal ischemia reperfusion injury (IRI) in mice. Mycosystema 34:311–320

    CAS  Google Scholar 

  52. Lu MY, Chen CC, Lee LY, Lin TW, Kuo CF et al (2015) N6-(2-hydroxyethyl) adenosine in the medicinal mushroom Cordyceps cicadae attenuates lipopolysaccharide-stimulated pro-inflammatory responses by suppressing TLR4-mediated NF-κB signaling pathways. J Nat Prod 78:2452–2460

    Article  CAS  PubMed  Google Scholar 

  53. Fang M, Chai YQ, Chen GV, Wang HD, Huang B (2016) N-6-(2-hydroxyethyl)-adenosine exhibits insecticidal activity against Plutella xylostella via adenosine receptors. PLoS One 11:e0162859

    Article  PubMed  PubMed Central  Google Scholar 

  54. Chai YQ, Chen GJ, ** YW, Liu YG, Li XL et al., (2015) Use of N6-(2-hydroxyethyl)-adenosine in preparation of crop pesticide. USA, US20140256669 A1

    Google Scholar 

  55. Lee JS, Kwon JS, Won DP, Lee KE, Shin WC et al (2010a) Study on macrophage activation and structural characteristics of purified polysaccharide from the liquid culture broth of Cordyceps militaris. Carbohydr Polym 82:982–988

    Article  CAS  Google Scholar 

  56. Lee JS, Kwon JS, Yun JS, Pahk JW, Shin WC et al (2010b) Structural characterization of immunostimulating polysaccharide from cultured mycelia of Cordyceps militaris. Carbohydr Polym 80:1011–1017

    Article  CAS  Google Scholar 

  57. Smiderle FR, Sassaki GL, Griensven LV, Iacomini M (2013) Isolation and chemical characterization of a glucogalactomannan of the medicinal mushroom Cordyceps militaris. Carbohydr Polym 97:74–80

    Article  CAS  PubMed  Google Scholar 

  58. Yu RM, Yang W, Song LY, Yan CY, Zhang Z et al (2007) Structural characterization and antioxidant activity of a polysaccharide from the fruiting bodies of cultured Cordyceps militaris. Carbohydr Polym 70:430–436

    Article  CAS  Google Scholar 

  59. Chen R, ** CG, Li HP, Liu ZQ, Lu J et al (2014) Ultrahigh pressure extraction of polysaccharides from Cordyceps militaris and evaluation of antioxidant activity. Sep Purif Technol 134:90–99

    Article  CAS  Google Scholar 

  60. Dong CH, Guo SP, Wang WF, Liu XZ (2015) Cordyceps industry in China. Mycology 6:121–129

    Article  PubMed  PubMed Central  Google Scholar 

  61. Rodrigues C, Sousa C, Lopes JA, Novais A, Peixe L (2020) A front line on klebsiella pneumoniae capsular polysaccharide knowledge: fourier transform infrared spectroscopy as an accurate and fast ty** tool. Msystems 5:e00386–e00319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Sims IM, Frese SA, Walter J, Loach D, Wilson M et al (2011) Structure and functions of exopolysaccharide produced by gut commensal Lactobacillus reuteri 100-23. ISME J 5:1115–1124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Zhang J, Wen C, Gu J, Ji C, Duan Y et al (2019) Effects of subcritical water extraction microenvironment on the structure and biological activities of polysaccharides from Lentinus edodes. Int J Biol Macromol 123:1002–1011

    Article  CAS  PubMed  Google Scholar 

  64. Li SP, Li P, Lai CM, Gong YX, Kan KKW et al (2004) Simultaneous determination of ergosterol, nucleosides and their bases from natural and cultured Cordyceps by pressurized liquid extraction and high-performance liquid chromatography. J Chromatogr A 1036:239–243

    Article  CAS  PubMed  Google Scholar 

  65. Dupont S, Lemetais G, Ferreira T, Cayot P, Gervais P et al (2012) Ergosterol biosynthesis: a fungal pathway for life on land? Evolution 66:2961–2968

    Article  CAS  PubMed  Google Scholar 

  66. Chen YJ, Wu YQ, Li SL, Du SM, Hao XM et al (2021) Large-scale isolation and antitumor mechanism evaluation of compounds from the traditional Chinese medicine Cordyceps militaris. Eur J Med Chem 212:113142

    Article  CAS  PubMed  Google Scholar 

  67. Dong ZH, Sun YY, Wei GG, Li SY, Zhao ZX (2019) Ergosterol ameliorates diabetic nephropathy by attenuating mesangial cell proliferation and extracellular matrix deposition via the TGF-β1/Smad2 signaling pathway. Nutrients 11:483–500

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Yazawa Y, Ikarashi N, Hoshino M, Kikkawa H, Sakuma F (2020) Inhibitory effect of ergosterol on bladder carcinogenesis is due to androgen signaling inhibition by brassicasterol, a metabolite of ergosterol. J Nat Med 74:680–688

    Article  CAS  PubMed  Google Scholar 

  69. Chatterjee R, Srinivasan KS, Maiti PC (1957) Cordyceps sinensis (Berkeley) saccardo: structure of cordycepic acid. J Am Pharm Assoc 46:114–118

    Article  CAS  Google Scholar 

  70. Ouyang YY, Zhang Z, Cao YR, Zhang YQ, Tao YY et al (2013) Effects of cordyceps acid and cordycepin on the inflammatory and fibrogenic response of hepatic stellate cells. Chin J Hepatol 21:275–278

    CAS  Google Scholar 

  71. Wang Y, Yang ZS, Bao DP, Li B, Yin X et al (2021) Improving hypoxia adaption causes distinct effects on growth and bioactive compounds synthesis in an entomopathogenic fungus cordyceps militaris. Front Microbiol 12:698436

    Article  PubMed  PubMed Central  Google Scholar 

  72. Rao AV, Rao LG (2007) Carotenoids and human health. Hawaii Med J 55:207–216

    CAS  Google Scholar 

  73. Britton G (1995) Structure and properties of carotenoids in relation to function. FASEB J 9:1551–1558

    Article  CAS  PubMed  Google Scholar 

  74. Yang Y, Bu N, Wang S, Zhang J, Wang Y et al (2020) Carotenoid production by caterpillar medicinal mushrooms, Cordyceps militaris (Ascomycetes), under different culture conditions. Int J Med Mushrooms 22:1191–1201

    Article  PubMed  Google Scholar 

  75. Dong JZ, Wang SH, Ai XR, Yao L, Sun ZW, Can L (2013) Composition and characterization of cordyxanthins from cordyceps militaris fruit bodies. J Funct Food 5:1450–1455

    Article  CAS  Google Scholar 

  76. Yan XT, Bao HY, Bau T (2010) Isolation and identification of one natural pigment from cultured Cordyceps militaris. Mygosystema 29:777–781

    CAS  Google Scholar 

  77. Yang T, Sun JD, Lian TT, Wang WZ, Dong CH (2014) Process optimization for extraction of carotenoids from medicinal caterpillar fungus, Cordyceps militaris (Ascomycetes). Int J Med Mushrooms 16:125–135

    Article  CAS  PubMed  Google Scholar 

  78. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The hallmarks of aging. Cell 153:1194–1217

    Article  PubMed  PubMed Central  Google Scholar 

  79. Tan BL, Norhaizan ME, Liew WPP, Rahman HS (2018) Antioxidant and oxidative stress: a mutual interplay in age-related diseases. Front Pharmacol 9:1162

    Article  PubMed  PubMed Central  Google Scholar 

  80. Blount JD, Metcalfe NB, Birkhead TR, Surai PF (2003) Carotenoid modulation of immune function and sexual attractiveness in zebra finches. Science 300:125–127

    Article  CAS  PubMed  Google Scholar 

  81. Nagao A (2009) Absorption and function of dietary carotenoids. Forum Nutr 61:55–63

    Article  CAS  PubMed  Google Scholar 

  82. Yan XH, Qi QY, Wang SH, Wang CS (2016) Isolation and identification of bioactive compounds from Cordyceps militaris. Mycosystema 2016(35):605–610

    Google Scholar 

  83. Wang Z, He Z, Li S, Yuan Q (2005) Purification and partial characterization of cu, Zn containing superoxide dismutase from entomogenous fungal species cordyceps militaris. Enzym Microb Technol 36:862–869

    Article  Google Scholar 

  84. Rukachaisirikul V, Pramjit S, Pakawatchai C, Isaka M, Supothina S (2004) 10-membered macrolides from the insect pathogenic fungus Cordyceps militaris BCC 2816. J Nat Prod 67:1953–1955

    Article  CAS  PubMed  Google Scholar 

  85. Jung EC, Kim KD, Bae CH, Kim JC, Kim DK et al (2007) A mushroom lectin from ascomycete Cordyceps militaris. Biochim Biophys Acta Gen Subj 1770:833–838

    Article  CAS  Google Scholar 

  86. Chiu CP, Liu SC, Tang CH, Chan Y, Mohamed ES et al (2016) Anti-inflammatory cerebrosides from cultivated Cordyceps militaris. J Agric Food Chem 64:1540–1548

    Article  CAS  PubMed  Google Scholar 

  87. Sun JB, Xu J, Wang S, Hou ZD, Lu XC et al (2019a) A new cerebroside from Cordyceps militaris with anti-PTP1B activity. Fitoterapia 138:104342

    Article  CAS  PubMed  Google Scholar 

  88. Wang J, Chen HL, Li WR, Shan LL (2020) Cordyceps acid alleviates lung cancer in nude mice. J Biochem Mol Toxicol 35:e22670

    PubMed  Google Scholar 

  89. Elkhateeb WA, Daba GM, Thomas P, Wen TC (2019) Medicinal mushrooms as a new source of natural therapeutic bioactive compounds. Egypt Pharm J 18:88–101

    Google Scholar 

  90. Huenga DY, Hsieh CH, Cheng YC, Tsai WC, Chen Y (2017) Cordycepin inhibits migration of human glioblastoma cells by affecting lysosomal degradation and protein phosphatase activation. J Nutr Biochem 41:109–116

    Article  Google Scholar 

  91. Bawadekji A, Ali KA, Ali MA (2016) A review of the bioactive compound and medicinal value of Cordyceps militaris. North J Appl For 1:69–76

    Google Scholar 

  92. Liu Y, Wang JH, Wang W, Zhang HY, Zhang XL et al (2015) The chemical constituents and pharmacological actions of Cordyceps sinensis. Evid Based Complement Altern Med 2015:1–12

    Google Scholar 

  93. Kwon HW, Shin JH, Lim DH, Ok WJ, Nam GS et al (2016) Antiplatelet and antithrombotic effects of cordycepin-enriched WIB-801CE from Cordyceps militaris ex vivo, in vivo, and in vitro. BMC Complement Altern Med 16:508

    Article  PubMed  PubMed Central  Google Scholar 

  94. Cui JD (2015) Biotechnological production and applications of Cordyceps militaris, a valued traditional Chinese medicine. Crit Rev Biotechnol 35:475–484

    Article  CAS  PubMed  Google Scholar 

  95. Liao YH, Ling JY, Zhang GY, Liu FJ, Tao S et al (2015) Cordycepin induces cell cycle arrest and apoptosis by inducing DNA damage and up-regulation of p53 in Leukemia cells. Cell Cycle 14:761–771

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Wu WD, Hu ZM, Shang MJ, Zhao DJ, Huang DS (2014) Cordycepin down-regulates multiple drug resistant (MDR)/HIF-1α through regulating AMPK/mTORC1 signaling in GBC-SD gallbladder cancer cells. Int J Mol Sci 15:12778–12790

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Lee SK, Lee JH, Kim HR, Chun Y, Lee JH et al (2019) Improved cordycepin production by Cordyceps militaris KYL05 using casein hydrolysate in submerged conditions. Biomol Ther 9:461

    CAS  Google Scholar 

  98. Lee JS, Kwon DS, Lee KR, Park JM, Ha SJ et al (2015) Mechanism of macrophage activation induced by polysaccharide from cordyceps militaris culture broth. Carbohydr Polym 120:29–37

    Article  CAS  PubMed  Google Scholar 

  99. Kim HS, Kim JY, Kang JS, Kim HM, Kim YO et al (2010) Cordlan polysaccharide isolated from mushroom Cordyceps militaris induces dendritic cell maturation through toll-like receptor 4 signalings. Food Chem Toxicol 48:1926–1933

    Article  CAS  PubMed  Google Scholar 

  100. Kwon JS, Lee JS, Shin WC, Lee KE, Hong EK (2009) Optimization of culture conditions and medium components for the production of mycelial biomass and exo-polysaccharides with Cordyceps militaris in liquid culture. Biotechnol Bioprocess Eng 14:756–762

    Article  CAS  Google Scholar 

  101. Cheung JH, Li J, Cheung AWH, Yue Z, Zheng KYZ et al (2009) Cordysinocan, a polysaccharide isolated from cultured Cordyceps, activates immune responses in cultured T-lymphocytes and macrophages: Signaling cascade and induction of cytokines. J Ethnopharmacol 124:61–68

    Article  CAS  PubMed  Google Scholar 

  102. Else M, Dearden CE, Matutes E, Forconi F, Lauria F et al (2011) Rituximab with pentostatin or cladribine: an effective combination treatment for hairy cell leukemia after disease recurrence. Leuk Lymphoma 52:75–78

    Article  CAS  PubMed  Google Scholar 

  103. Li XG, Wu QP, **e YZ, Ding YR, Du WW et al (2015) Ergosterol purified from medicinal mushroom Amauroderma rude inhibits cancer growth in vitro and in vivo by up-regulating multiple tumor suppressors. Oncotarget 6:17832–17846

    Article  PubMed  PubMed Central  Google Scholar 

  104. Yasukawa K, Aoki T, Takido M, Ikekawa T, Saito H et al (1994) Inhibitory effects of ergosterol isolated from the edible mushroom hypsizigus marmoreus on tpa-induced inflammatory ear edema and tumor promotion I mice. Phytother Res 8:10–13

    Article  CAS  Google Scholar 

  105. Yoo HS, Shin JW, Cho JH, Son CG, Lee YW et al (2004) Effects of Cordyceps militaris extract on angiogenesis and tumor growth. Acta Pharmacol Sin 25:657–665

    CAS  PubMed  Google Scholar 

  106. Park BT, Na KH, Jung EC, Park JW, Kim HH (2009a) Antifungal and anticancer activities of a protein from the mushroom Cordyceps militaris. Korean J Physiol Pharmacol 13:49–54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Park SE, Kim J, Lee YW, Yoo HS, Cho CK (2009b) Antitumor activity of water extracts from Cordyceps militaris in NCI-H460 cell xenografted nude mice. J Acupunct Meridian Stud 2:294–300

    Article  PubMed  Google Scholar 

  108. Mollah ML, Dong KP, Park HJ (2012) Cordyceps militaris grown on germinated soybean induces G2/M cell cycle arrest through downregulation of cyclin B1 and Cdc25c in human colon cancer HT-29 cells. Evid Based Complement Altern Med 2012:249217

    Article  Google Scholar 

  109. Shang XL, Pan LC, Tang Y, Luo Y, Zhu ZY et al (2020) H-1 NMR-based metabonomics of the hypoglycemic effect of polysaccharides from Cordyceps militaris on streptozotocin-induced diabetes in mice. Nat Prod Res 34:1366–1372

    Article  CAS  PubMed  Google Scholar 

  110. Jo WS, Choi YJ, Kim HJ, Lee JY, Nam BH, Lee JD (2010) The anti-inflammatory effects of water extract from cordyceps militaris in murine macrophage. Mycobiology 38:46–51

    Article  PubMed  PubMed Central  Google Scholar 

  111. ** C, Kim G, Choi Y (2008) Induction of apoptosis by aqueous extract of cordyceps militaris through activation of caspases and inactivation of Akt in human breast cancer MDA-MB-231 cells. J Microbiol Biotechnol 18:1997–2003

    CAS  PubMed  Google Scholar 

  112. He BL, Zheng QW, Guo LQ, Huang JY, Yun F et al (2020) Structural characterization and immune-enhancing activity of a novel high-molecular-weight polysaccharide from Cordyceps militaris. Int J Biol Macromol 145:11–20

    Article  CAS  PubMed  Google Scholar 

  113. Rao YK, Fang SH, Wu WS, Tzeng YM (2010) Constituents isolated from cordyceps militaris suppress enhanced inflammatory mediator's production and human cancer cell proliferation. J Ethnopharmacol 131:363–367

    Article  CAS  PubMed  Google Scholar 

  114. Chu HL, Chien JC, Duh PD (2011) Protective effect of Cordyceps militaris against high glucose-induced oxidative stress in human umbilical vein endothelial cells. Food Chem 129:871–876

    Article  CAS  PubMed  Google Scholar 

  115. Nan JX, Park EJ, Yang BK, Song CH, Ko G et al (2001) Antifibrotic effect of extracellular biopolymer from submerged mycelial cultures of Cordyceps militaris on liver fibrosis induced by bile duct ligation and scission in rats. Arch Pharm Res 24:327

    Article  CAS  PubMed  Google Scholar 

  116. Sun T, Dong W, Jiang G, Yang J, Liu J et al (2019b) Cordyceps militaris improves chronic kidney disease by affecting TLR4/NF-κB redox signaling pathway. Oxidative Med Cell Longev 2019:7850863

    Article  Google Scholar 

  117. Rupa EJ, Li JF, Arif MH, Yaxi H, Puja AM et al (2020) Cordyceps militaris fungus extracts-mediated nanoemulsion for improvement antioxidant, antimicrobial, and anti-inflammatory activities. Molecules 25:5733

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Tran NKS, Kim GT, Park SH, Lee D, Shim SM et al (2019) Fermented Cordyceps militaris extract prevents hepatosteatosis and adipocyte hypertrophy in high fat diet-fed mice. Nutrients 13:50

    Google Scholar 

  119. Lin RK, Choong CY, Hsu WH, Tai CJ, Tai CJ (2019) Polysaccharides obtained from mycelia of Cordyceps militaris attenuated doxorubicin-induced cytotoxic effects in chemotherapy. Afr Health Sci 19:2156–2163

    Article  PubMed  PubMed Central  Google Scholar 

  120. Kim J, Lee H, Kang KS, Chun KH, Hwang GS (2015) Cordyceps militaris mushroom and Cordycepin inhibit rankl-induced osteoclast differentiation. J Med Food 18:446–452

    Article  PubMed  Google Scholar 

  121. Hu SM, Wang J, Li FH, Hou PB, Yin JY, Yang ZX (2019) Structural characterisation and cholesterol efflux improving capacity of the novel polysaccharides from Cordyceps militaris. Int J Biol Macromol 131:264–272

    Article  CAS  PubMed  Google Scholar 

  122. Song QY, Zhu ZY (2020) Using Cordyceps militaris extracellular polysaccharides to prevent Pb2+-induced liver and kidney toxicity by activating Nrf2 signals and modulating gut microbiota. Food Funct 11:9226–9239

    Article  CAS  PubMed  Google Scholar 

  123. Wu TF, Shi WY, Chiu YC, Chan YY (2021) Investigation of the molecular mechanism underlying the inhibitory activities of ethanol extract of Bombyx mori pupa-incubated Cordyceps militaris fruiting bodies toward allergic rhinitis. Biomed Pharmacother 135:111248

    Article  CAS  PubMed  Google Scholar 

  124. Yang XQ, Lin P, Wang J, Liu N, Yin F et al (2021) Purification, characterization and anti-atherosclerotic effects of the polysaccharides from the fruiting body of Cordyceps militaris. Int J Biol Macromol 181:890–904

    Article  CAS  PubMed  Google Scholar 

  125. Lin YE, Chen YC, Lu KH, Huang YJ, Panyod S et al (2021) Antidepressant-like effects of water extract of Cordyceps militaris (Linn.) link by modulation of ROCK2/PTEN/Akt signaling in an unpredictable chronic mild stress-induced animal model. J Ethnopharmacol 276:114194

    Article  CAS  PubMed  Google Scholar 

  126. Gallo A, Ferrara M, Perrone G (2013) Phylogenetic study of polyketide synthases and nonribosomal peptide synthetases involved in the biosynthesis of mycotoxins. Toxins 5:717–742

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Zheng P, **a YL, **ao GH, **ong CH, Hu X et al (2011) Genome sequence of the insect pathogenic fungus Cordyceps militaris, a valued traditional Chinese medicine. Genome Biol 35:475–484

    Google Scholar 

  128. Jhou BY, Fang WC, Chen YL, Chen CC (2018) A 90-day subchronic toxicity study of submerged mycelial culture of Cordyceps militaris in rats. Toxicol Res 7:977–986

    Article  CAS  Google Scholar 

  129. Heo JY, Baik HW, Kim HJ, Lee JM, Kim HW et al (2015) The efficacy and safety of Cordyceps militaris in Korean adults who have mild liver dysfunction. J Clin Nutr 7:81–86

    Article  Google Scholar 

  130. Aramwit P, Porasuphatana S, Srichana T, Nakpheng T (2015) Toxicity evaluation of cordycepin and its delivery system for sustained in vitro anti-lung cancer activity. Nanoscale Res Lett 10:152–161

    Article  PubMed  PubMed Central  Google Scholar 

  131. Pintathong P, Chomnunti P, Sangthong S, Jirarat A, Chaiwut P (2021) The feasibility of utilizing cultured Cordyceps militaris residues in cosmetics: biological activity assessment of their crude extracts. J Fungi 7:973

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Caihong Dong .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Liu, M., Li, X., Huai, M., Yang, Y., Dong, C. (2023). Cultivation, Bioactive Metabolites, and Application of Caterpillar Mushroom Cordyceps militaris: Current State, Issues, and Perspectives. In: Satyanarayana, T., Deshmukh, S.K. (eds) Fungi and Fungal Products in Human Welfare and Biotechnology. Springer, Singapore. https://doi.org/10.1007/978-981-19-8853-0_7

Download citation

Publish with us

Policies and ethics

Navigation