Advertisement

Cordycepin: A Biotherapeutic Molecule from Medicinal Mushroom

  • Mohammad Soltani
  • Roslinda Abd Malek
  • Nagib A. Elmarzugi
  • Mohamad Fawzi Mahomoodally
  • Davin Uy
  • Ong Mei Leng
  • Hesham A. El-EnshasyEmail author
Chapter
Part of the Fungal Biology book series (FUNGBIO)

Abstract

Cordyceps is one of the most well-known mushroom with numerous bioactive compounds possess wide range of biotherapeutic activities. This mushroom has been used for many years as medicinal food particularly in China and in different regions of south East Asia. Cordycepin is a nucleoside compound extracted from different species of Cordyceps and considered as one of the most important bioactive metabolites of this fungus. This low molecular weight compound exhibit several medicinal functions as anticancer, antitumor, antioxidant, anti-inflammatory, hypoglycemic, immunomodulatory agent. In this chapter we reviewed recent published research on the cordycepin chemistry, production, extraction, isolation, purification, biotherapeutic activities and applications.

Keywords

Medicinal mushroom Cordyceps Cordycepin Bioatherapeutic Anticancer Immunomodulator 

Notes

Acknowledgement

The financial support from the Institute of Bioproduct Development (IBD), is gratefully acknowledged. We would like also to acknowledge the support of MOHE and UTM-RMC through HICOE grant no.R.J130000.7846.4 J262.

References

  1. Ahn YJ, Park SJ, Lee SG, Shin SC, Choi DH (2006) Cordycepin: selective growth inhibitor derived from liquid culture of cordyceps militaris against clostridium spp. J Agric Food Chem 48(7):2744–2748CrossRefGoogle Scholar
  2. Aman S, Anderson DJ, Connolly TJ, Crittall AJ, Ji G (2000) From adenosine to 3 ‘-deoxyadenosine: development and scale up. Org Process Res Dev 4(6):601–605CrossRefGoogle Scholar
  3. Bok JW, Lermer L, Chilton J, Klingeman HG, Towers GN (1999) Antitumor sterols from the mycelia of Cordyceps sinensis. Phytochemistry 51(7):891–898PubMedCrossRefPubMedCentralGoogle Scholar
  4. Buenz EJ, Bauer BA, Osmundson TW, Motley TJ (2005) The traditional Chinese medicine Cordyceps sinensis and its effects on apoptotic homeostasis. J Ethnopharmacol 96(1–2):19–29PubMedCrossRefPubMedCentralGoogle Scholar
  5. Chang W, Lim S, Song H, Song BW, Kim HJ, Cha MJ, Sung JM, Kim TW, Hwang KC (2008) Cordycepin inhibits vascular smooth muscle cell proliferation. Eur J Pharmacol 597(1–3):64–69PubMedCrossRefPubMedCentralGoogle Scholar
  6. Chen LS, Stellrecht CM, Gandhi V (2008) RNA-directed agent, cordycepin, induces cell death in multiple myeloma cells. Br J Haematol 140(6):682–391PubMedCrossRefPubMedCentralGoogle Scholar
  7. Chen M, Cheung FW, Chan MH, Hui PK, Ip SP, Ling YH, Che CT, Liu WK (2012) Protective roles of Cordyceps on lung fibrosis in cellular and rat models. J Ethnopharmacol 143(2):448–454PubMedCrossRefPubMedCentralGoogle Scholar
  8. Chen ZG, Zhang DN, Cao L, Han YB (2013) Highly efficient and region selective acylation of pharmacologically interesting cordycepin catalyzed by lipase in the eco-friendly solvent 2-methyltetrahydrofuran. Bioresour Technol 133:82–86PubMedCrossRefPubMedCentralGoogle Scholar
  9. Cheng Z, He W, Zhou X, Lv Q, Xu X, Yang S, Zhao C, Guo L (2011) Cordycepin protects against cerebral ischemia/reperfusion injury in vivo and in vitro. Eur J Pharmacol 664(1–3):20–28PubMedCrossRefPubMedCentralGoogle Scholar
  10. Cho HJ, Cho JY, Rhee MH, Park HJ (2007) Cordycepin (3′-deoxyadenosine) inhibits human platelet aggregation in a cyclic AMP-and cyclic GMP-dependent manner. Eur J Pharmacol 558(1–3):43–51PubMedCrossRefPubMedCentralGoogle Scholar
  11. Choi S, Lim MH, Kim KM, Jeon BH, Song WO, Kim TW (2011) Cordycepin-induced apoptosis and autophagy in breast cancer cells are independent of the estrogen receptor. Toxicol Appl Pharmacol 257(2):165–173PubMedCrossRefPubMedCentralGoogle Scholar
  12. Choi YH, Kim GY, Lee HH (2014) Anti-inflammatory effects of cordycepin in lipopolysaccharide-stimulated RAW 264.7 macrophages through Toll-like receptor 4-mediated suppression of mitogen-activated protein kinases and NF-κB signaling pathways. Drug Des Devel Ther 8:1941PubMedPubMedCentralCrossRefGoogle Scholar
  13. Cory JG, Suhadolnik RJ, Resnick B, Rich MA (1965) Incorporation of cordycepin (3′-deoxyadenosine) into ribonucleic acid and deoxyribonucleic acid of human tumor cells. Biochim Biophys Acta 103(4):646–653PubMedCrossRefPubMedCentralGoogle Scholar
  14. Cunningham KG (1951) Cordycepin, a metabolic product from cultures of Cordyceps militaris (Linn) Link. Part I. Isolation and characterization. J Chem Soc 2:2299–2302CrossRefGoogle Scholar
  15. Da Silva AS, Wolkmer P, Nunes JT, Duck MR, Oliveira CB, Gressler LT, Costa MM, Zanette RA, Mazzanti CM, Lopes ST, Monteiro SG (2011) Susceptibility of Trypanosoma evansi to cordycepin. Biomed Pharmacother 65(3):220–223PubMedCrossRefPubMedCentralGoogle Scholar
  16. Das S, Masuda M, Sakurai A, Sakakibara M (2009) Effects of additives on cordycepin production using a Cordyceps militaris mutant induced by ion beam irradiation. Afr J Biotechnol 8(13):3041–3047Google Scholar
  17. Das SK, Fujihara S, Masuda M, Sakurai A (2016) Efficient production of anticancer agent cordycepin by repeated batch culture of Cordyceps militaris mutant. WCECS 2010, San Francisco, USA. World Congress on Engineering and Computer Science 2010Google Scholar
  18. Dou C, Cao Z, Ding N, Hou T, Luo F, Kang F, Yang X, Jiang H, Xie Z, Hu M, Xu J (2016) Cordycepin prevents bone loss through inhibiting osteoclastogenesis by scavenging ROS generation. Nutrients 8(4):231PubMedPubMedCentralCrossRefGoogle Scholar
  19. El Enshasy H, Elsayed EA, Aziz R, Wadaan MA (2013) Mushrooms and truffles: historical biofactories for complementary medicine in Africa and in the middle East. Evid Based Complement Alternat Med 2013:1–10CrossRefGoogle Scholar
  20. El Enshasy HE (2010) Immunomodulators. In: Hofrichter M (ed) Mycota, 2nd edn. Springer Verlag, Heidelberg, pp 165–194Google Scholar
  21. El Enshasy HA, Hatti-Kaul R (2013) Mushroom immunomodulators: unique molecules with unlimited applications. Trends Biotechnol 31(12):668–677PubMedCrossRefPubMedCentralGoogle Scholar
  22. Fan DD, Wang W, Zhong JJ (2012) Enhancement of cordycepin production in submerged cultures of Cordyceps militaris by addition of ferrous sulfate. Biochem Eng J 60:30–35CrossRefGoogle Scholar
  23. Fan H, Li SP, Xiang JJ, Lai CM, Yang FQ, Gao JL, Wang YT (2006) Qualitative and quantitative determination of nucleosides, bases and their analogues in natural and cultured Cordyceps by pressurized liquid extraction and high performance liquid chromatography–electrospray ionization tandem mass spectrometry (HPLC–ESI–MS/MS). Anal Chim Acta 567(2):218–228CrossRefGoogle Scholar
  24. Fujita T, Inoue K, Yamamot OS, Ikumoto T, Sasaki S, Toyama R, Chiba K, Hoshino Y, Okumoto T (1994) Fungal metabolites. Part 11. A potent immunosuppressive activity found in Isaria sinclairii metabolite. J Antibiot (Tokyo) 47(2):208–215CrossRefGoogle Scholar
  25. Hansske F, Robins MJ (1985) Regiospecific and stereoselective conversion of ribonucleosides to 3-deoxynucleosides. A high yield three-stage synthesis of cordycepin from adenosine. Tetrahedron Lett 26(36):4295–4298CrossRefGoogle Scholar
  26. Holbein S, Wengi A, Decourty L, Freimoser FM, Jacquier A, Dichtl B (2009) Cordycepin interferes with 3′ end formation in yeast independently of its potential to terminate RNA chain elongation. RNA 15(5):837–849PubMedPubMedCentralCrossRefGoogle Scholar
  27. Hsu TH, Shiao LH, Hsieh C, Chang DM (2002) A comparison of the chemical composition and bioactive ingredients of the Chinese medicinal mushroom Dong Chong XiaCao, its counterfeit and mimic, and fermented mycelium of Cordyceps sinensis. Food Chem 78(4):463–469CrossRefGoogle Scholar
  28. Hu Z, Lee CI, Shah VK, Oh EH, Han JY, Bae JR, Lee K, Chong MS, Hong JT, Oh KW (2013) Cordycepin increases nonrapid eye movement sleep via adenosine receptors in rats. Evid Based Complement Alternat Med:2013Google Scholar
  29. Jeong JW, Jin CY, Kim GY, Lee JD, Park C, Kim GD, Kim WJ, Jung WK, Seo SK, Choi IW, Choi YH (2010) Anti-inflammatory effects of cordycepin via suppression of inflammatory mediators in BV2 microglial cells. Int Immunopharmacol 10(12):1580–1586PubMedCrossRefPubMedCentralGoogle Scholar
  30. Jeong JW, Jin CY, Park C, Hong SH, Kim GY, Jeong YK, Lee JD, Yoo YH, Choi YH (2011) Induction of apoptosis by cordycepin via reactive oxygen species generation in human leukemia cells. Toxicol In Vitro 25(4):817–824PubMedCrossRefPubMedCentralGoogle Scholar
  31. Jeong MH, Lee CM, Lee SW, Seo SY, Seo MJ, Kang BW, Jeong YK, Choi YJ, Yang KM, Jo WS (2013) Cordycepin-enriched Cordyceps militaris induces immunomodulation and tumor growth delay in mouse-derived breast cancer. Oncol Rep 30(4):1996–2002PubMedCrossRefPubMedCentralGoogle Scholar
  32. Jiapeng T, Yiting L, Li Z (2014) Optimization of fermentation conditions and purification of cordycepin from Cordyceps militaris. Prep Biochem Biotechnol 44(1):90–106PubMedCrossRefPubMedCentralGoogle Scholar
  33. Jung SM, Park SS, Kim WJ, Moon SK (2012) Ras/ERK1 pathway regulation of p27KIP1-mediated G1-phase cell-cycle arrest in cordycepin-induced inhibition of the proliferation of vascular smooth muscle cells. Eur J Pharmacol 681(1–3):15–22PubMedCrossRefPubMedCentralGoogle Scholar
  34. Kang C, Wen TC, Kang JC, Meng ZB, Li GR, Hyde KD (2014) Optimization of large-scale culture conditions for the production of cordycepin with Cordyceps militaris by liquid static culture. Sci World J 2014:2014Google Scholar
  35. Kiho T, Ukai ST (1995) (Semitake and others), Cordyceps species. Food Rev Int 11(1):231–234CrossRefGoogle Scholar
  36. Kim HG, Shrestha B, Lim SY, Yoon DH, Chang WC, Shin DJ, Han SK, Park SM, Park JH, Park HI, Sung JM (2006) Cordycepin inhibits lipopolysaccharide-induced inflammation by the suppression of NF-κB through Akt and p38 inhibition in RAW 264.7 macrophage cells. Eur J Pharmacol 545(2–3):192–199PubMedCrossRefPubMedCentralGoogle Scholar
  37. Kim HO, Yun JW (2005) A comparative study on the production of exopolysaccharides between two entomopathogenic fungi Cordyceps militaris and Cordyceps sinensis in submerged mycelial cultures. J Appl Microbiol 99(4):728–738PubMedCrossRefPubMedCentralGoogle Scholar
  38. Klenow H (1963) Formation of the mono-, di-and triphosphate of cordycepin in Ehrlich ascites-tumor cells in vitro. Biochim Biophys Acta (BBA) 76:347–353CrossRefGoogle Scholar
  39. Ko BS, Lu YJ, Yao WL, Liu TA, Tzean SS, Shen TL, Liou JY (2013) Cordycepin regulates GSK-3β/β-catenin signaling in human leukemia cells. PLoS One 8(9):e76320PubMedPubMedCentralCrossRefGoogle Scholar
  40. Kodama EN, McCaffrey RP, Yusa K, Mitsuya H (2000) Antileukemic activity and mechanism of action of cordycepin against terminal deoxynucleotidyl transferase-positive (TdT+) leukemic cells. Biochem Pharmacol 59(3):273–281PubMedCrossRefPubMedCentralGoogle Scholar
  41. Kubota Y, Kunikata M, Ishizaki N, Haraguchi K, Odanaka Y, Tanaka H (2008) Synthesis of 4-benzoyloxycordycepin from adenosine. Tetrahedron 64(10):2391–2396CrossRefGoogle Scholar
  42. Lee DH, Kim HH, Lim DH, Kim JL, Park HJ (2015) Effect of cordycepin-enriched WIB801C from Cordyceps militaris suppressing fibrinogen binding to glycoprotein IIb/IIIa. Biomol Ther (Seoul) 23(1):60–70CrossRefGoogle Scholar
  43. Lee SJ, Kim SK, Choi WS, Kim WJ, Moon SK (2009) Cordycepin causes p21WAF1-mediated G2/M cell-cycle arrest by regulating c-Jun N-terminal kinase activation in human bladder cancer cells. Arch Biochem Biophys 490(2):103–109PubMedCrossRefPubMedCentralGoogle Scholar
  44. Lee SJ, Moon GS, Jung KH, Kim WJ, Moon SK (2010) c-Jun N-terminal kinase 1 is required for cordycepin-mediated induction of G2/M cell-cycle arrest via p21WAF1 expression in human colon cancer cells. Food Chem Toxicol 48(1):277–283PubMedCrossRefPubMedCentralGoogle Scholar
  45. Leung PH, Wu JY (2007) Effects of ammonium feeding on the production of bioactive metabolites (cordycepin and exopolysaccharides) in mycelial culture of a Cordyceps sinensis fungus. J Appl Microbiol 103(5):1942–1949PubMedCrossRefPubMedCentralGoogle Scholar
  46. Leung PH, Zhang QX, Wu JY (2006) Mycelium cultivation, chemical composition and antitumour activity of a Tolypocladium sp. fungus isolated from wild Cordyceps sinensis. J Appl Microbiol 101(2):275–283PubMedCrossRefPubMedCentralGoogle Scholar
  47. Li SP, Li P, Lai CM, Gong YX, Kan KK, Dong TT, Tsim KW, Wang YT (2004) Simultaneous determination of ergosterol, nucleosides and their bases from natural and cultured Cordyceps by pressurised liquid extraction and high-performance liquid chromatography. J Chromatogr A 1036(2):239–243PubMedCrossRefPubMedCentralGoogle Scholar
  48. Lia J, Guanb M, Lic Y (2015) Effects of cooking on the contents of adenosine and cordycepin in Cordyceps militaris. In: The 7th World Congress on Particle Technology (WCPT7). Elsevier Ltd, China, pp 485–491Google Scholar
  49. Lin YW, Chiang BH (2008) Anti-tumor activity of the fermentation broth of Cordyceps militaris cultured in the medium of Radix astragali. Process Biochem 43(3):244–250CrossRefGoogle Scholar
  50. Ling JY, Sun YJ, Zhang H, Lv P, Zhang CK (2002) Measurement of cordycepin and adenosine in stroma of Cordyceps sp. by capillary zone electrophoresis (CZE). J Biosci Bioeng 94(4):371–374PubMedCrossRefPubMedCentralGoogle Scholar
  51. Ling JY, Zhang GY, Lin JQ, Cui ZJ, Zhang CK (2009) Supercritical fluid extraction of cordycepin and adenosine from Cordyceps kyushuensis and purification by high-speed counter-current chromatography. Sep Purif Technol 66(3):625–629CrossRefGoogle Scholar
  52. Ma L, Zhang S, Du M (2015) Cordycepin from Cordyceps militaris prevents hyperglycemia in alloxan-induced diabetic mice. Nutr Res 35(5):431–439PubMedCrossRefPubMedCentralGoogle Scholar
  53. Mao XB, Eksriwong T, Chauvatcharin S, Zhong JJ (2005) Optimization of carbon source and carbon/nitrogen ratio for cordycepin production by submerged cultivation of medicinal mushroom Cordyceps militaris (2005). Process Biochem 40(5):1667–1672CrossRefGoogle Scholar
  54. Mao XB, Zhong JJ (2004) Hyperproduction of cordycepin by two-stage dissolved oxygen control in submerged cultivation of medicinal mushroom Cordyceps militaris in bioreactors. Biotechnol Prog 20(5):1408–1413PubMedCrossRefPubMedCentralGoogle Scholar
  55. Mao XB, Zhong JJ (2006) Significant effect of NH4+ on cordycepin production by submerged cultivation of medicinal mushroom Cordyceps militaris. Enzym Microb Technol 38(3–4):343–350CrossRefGoogle Scholar
  56. Masuda M, Das SK, Fujihara S, Hatashita M, Sakurai A (2011) Production of cordycepin by a repeated batch culture of a Cordyceps militaris mutant obtained by proton beam irradiation. J Biosci Bioeng 111(1):55–60PubMedCrossRefPubMedCentralGoogle Scholar
  57. Masuda M, Das SK, Hatashita M, Fujihara S, Sakurai A (2014) Efficient production of cordycepin by the Cordyceps militaris mutant G81-3 for practical use. Process Biochem 49(2):181–187CrossRefGoogle Scholar
  58. Masuda M, Urabe E, Honda H, Sakurai A, Sakakibara M (2007) Enhanced production of cordycepin by surface culture using the medicinal mushroom Cordyceps militaris. Enzym Microb Technol 40(5):1199–1205CrossRefGoogle Scholar
  59. Masuda M, Urabe E, Sakurai A, Sakakibara M (2006) Production of cordycepin by surface culture using the medicinal mushroom Cordyceps militaris. Enzym Microb Technol 39(4):641–646CrossRefGoogle Scholar
  60. Mizuno T (1999) Medicinal effects and utilization of Cordyceps (Fr.) Link (Ascomycetes) and Isaria Fr. (Mitosporic Fungi) Chinese Caterpillar Fungi, “Tochukaso”. Int J Med Mushrooms 1(3):251–261CrossRefGoogle Scholar
  61. Muller WE, Weiler BE, Charubala R, Pfleiderer W, Leserman L, Sobol RW (1991) Cordycepin analogues of 2′, 5′ -oligoadenylate inhibit human immunodeficiency virus infection via inhibition of reverse transcriptase. Biochemistry 30:2027–2033PubMedCrossRefPubMedCentralGoogle Scholar
  62. Nakamura K, Konoha K, Yoshikawa N, Yamaguchi Y, Kagota S, Shinozuka K, Kunitomo MN (2005) Effect of cordycepin (3′-deoxyadenosine) on hematogenic lung metastatic model mice. In Vivo 19(1):137–141PubMedPubMedCentralGoogle Scholar
  63. Ng TB, Wang HX (2005) Pharmacological actions of Cordyceps, a prized folk medicine. J Pharm Pharmacol 57(12):1509–1519PubMedCrossRefPubMedCentralGoogle Scholar
  64. Ni H, Zhou XH, Li HH, Huang WF (2009) Column chromatographic extraction and preparation of cordycepin from Cordyceps militaris waster medium. J Chromatogr B 877(22):2135–2141CrossRefGoogle Scholar
  65. Overgaard-Hansen K (1964a) The inhibition of 5-phosphoribosyl-1-pyrophosphate formation by cordycepin triphosphate in extracts of Ehrlich ascites tumor cells. Biochim Biophys Acta 80(3):504–507PubMedPubMedCentralGoogle Scholar
  66. Overgaard-Hansen K (1964b) The inhibition of 5-phosphoribosyl-1-pyrophosphate formation by cordycepin triphosphate in extracts of Ehrlich ascites tumor cells. Biochim Biophys Acta 80:504–507PubMedPubMedCentralGoogle Scholar
  67. Pan BS, Wang YK, Lai MS, Mu YF, Huang BM (2015) Cordycepin induced MA-10 mouse Leydig tumor cell apoptosis by regulating p38 MAPKs and PI3K/AKT signaling pathways. Sci Rep 25(5):13372CrossRefGoogle Scholar
  68. Park HJ (2015) Ethanol extract of Cordyceps militaris grown on germinated soybeans inhibits 2, 4-dinitrophenolfluorobenzene-induced allergic contact dermatitis. J Funct Foods 1(17):938–947CrossRefGoogle Scholar
  69. Pegler DN, Yao YJ, Li Y (1994) The Chinese ‘caterpillar fungus’. Mycologist 8(1):3–5CrossRefGoogle Scholar
  70. Peng J, Wang P, Ge H, Qu X, Jin X (2015) Effects of cordycepin on the microglia-overactivation-induced impairments of growth and development of hippocampal cultured neurons. PLoS One 10(5):e0125902PubMedPubMedCentralCrossRefGoogle Scholar
  71. Ramesh T, Yoo SK, Kim SW, Hwang SY, Sohn SH, Kim IW, Kim SK (2012) Cordycepin (3′-deoxyadenosine) attenuates age-related oxidative stress and ameliorates antioxidant capacity in rats. Exp Gerontol 47(12):979–987PubMedCrossRefPubMedCentralGoogle Scholar
  72. Rao YK, Chou CH, Tzeng YM (2006) A simple and rapid method for identification and determination of cordycepin in Cordyceps militaris by capillary electrophoresis. Anal Chim Acta 566(2):253–258CrossRefGoogle Scholar
  73. Ren Z, Cui J, Huo Z, Xue J, Cui H, Luo B, Jiang L, Yang R (2012) Cordycepin suppresses TNF-α-induced NF-κB activation by reducing p65 transcriptional activity, inhibiting IκBα phosphorylation, and blocking IKKγ ubiquitination. Int Immunopharmacol 14(4):698–703PubMedCrossRefPubMedCentralGoogle Scholar
  74. Rich MA, Meyers P, Weinbaum G, Cory JG, Suhadolnik RJ (1965) Inhibition of human tumor cells by cordycepin. Biochim Biophys Acta 95(2):194–204PubMedCrossRefPubMedCentralGoogle Scholar
  75. Rottman F, Guarino AJ (1964) The inhibition of phosphoribosyl-pyrophosphate amidotransferase activity by cordycepin monophosphate. Biochem Biophys Acta 89:465–472PubMedPubMedCentralGoogle Scholar
  76. Soltani M, Kamyab H, El-Enshasy HA (2013) Molecular weight (Mw) and Monosaccharide composition (MC): Two major factors affecting the therapeutic action of polysaccharides extracted from Cordyceps sinensis. J Pure Appl Microbio 7(3):160111613Google Scholar
  77. Soltani M, Abd Malek R, Ware I, Ramli S, Elsayed EA, Aziz R (2017) Optimization of cordycepin extraction from Cordyceps militaris fermentation broth. J Sci Ind Res 76:355–361Google Scholar
  78. Suhadolnik RJ, Cory JG (1964) Further evidence for the biosynthesis of cordycepin and proof of the structure of 3-deoxyribose. Biochim Biophys Acta 91:661–662PubMedPubMedCentralGoogle Scholar
  79. Sun Y, Wang YH, Qu K, Zhu HB (2011) Beneficial effects of cordycepin on metabolic profiles of liver and plasma from hyperlipidemic hamsters. J Asian Nat Prod Res 13(06):534–546PubMedCrossRefPubMedCentralGoogle Scholar
  80. Tang YJ, Zhu LW, Li HM, Li DS (2007) Submerged culture of mushrooms in bioreactors-challenges, current state-of-the-art, and future prospects. Food Technol Biotechnol 45(3):221–229Google Scholar
  81. Tuli HS, Sandhu SS, Kashyap D, Sharma AK (2014a) Optimization of extraction conditions and antimicrobial potential of a bioactive metabolite, cordycepin from Cordyceps militaris 3936. WJPPS 3:1525–1535Google Scholar
  82. Tuli HS, Sandhu SS, Sharma AK (2014b) Pharmacological and therapeutic potential of Cordyceps with special reference to Cordycepin. 3 Biotech 4(1):1–2PubMedCrossRefGoogle Scholar
  83. Tuli HS, Sharma AK, Sandhu SS (2014c) Optimization of fermentation conditions for cordycepin production using Cordyceps militaris 3936. J Biol Chem Sci 1:35–47Google Scholar
  84. Velut S, de Maré L, Hagander P (2007) Bioreactor control using a probing feeding strategy and mid-ranging control. Control Eng Pract 15(2):135–147CrossRefGoogle Scholar
  85. Wang B-J, Won S-J, Yu Z-R, Su C-L (2005) Free radical scavenging and apoptotic effects of Cordyceps sinensis fractionated by supercritical carbon dioxide. Food Chem Toxicol 43:543–552PubMedCrossRefPubMedCentralGoogle Scholar
  86. Wang H-J, Pan M-C, Chang C-K, Chang S-W, Hsieh C-W (2014) Optimization of ultrasonic-assisted extraction of cordycepin from Cordyceps militaris using orthogonal experimental design. Molecules 19:20808–20820PubMedPubMedCentralCrossRefGoogle Scholar
  87. Wasser SP (2002) Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides. Appl Microbiol Biotechnol 60:258–274CrossRefGoogle Scholar
  88. Wei HP, Ye XL, Chen Z, Zhong YJ, Li PM, Pu SC, Li XG (2009) Synthesis and pharmacokinetic evaluation of novel N-acyl-cordycepin derivatives with a normal alkyl chain. Eur J Med Chem 44:665–669PubMedCrossRefPubMedCentralGoogle Scholar
  89. Won S-Y, Park E-H (2005) Anti-inflammatory and related pharmacological activities of cultured mycelia and fruiting bodies of Cordyceps militaris. J Ethnopharmacol 96:555–561PubMedCrossRefPubMedCentralGoogle Scholar
  90. Wong YY, Moon A, Duffin R, Barthet-Barateig A, Meijer HA, Clemens MJ, de Moor CH (2009) Cordycepin inhibits protein synthesis and cell adhesion through effects on signal transduction. J Biol Chem 23:jbc-M109Google Scholar
  91. Wu C, Guo Y, Su Y, Zhang X, Luan H, Zhang X, Zhu H, He H, Wang X, Sun G, Sun X, Guo P, Zhu P (2014) Cordycepin activates AMP-activated protein kinase (AMPK) via interaction with the γ1 subunit. J Cell Mol Med 18:293–304PubMedCrossRefPubMedCentralGoogle Scholar
  92. Wu JY, Zhang QX, Leung PH (2007) Inhibitory effects of ethyl acetate extract of Cordyceps sinensis mycelium on various cancer cells in culture and B16 melanoma in C57BL/6 mice. Phytomedicine 14:43–49PubMedCrossRefPubMedCentralGoogle Scholar
  93. Xie Huichun YL, Lao D, Zhang T, Ito Y (2011) Preparative separation of high-purity cordycepin from Cordyceps militaris(L.) link by high-speed countercurrent chromatography. J Liq Chromatogr Relat Technol 34:491–499CrossRefGoogle Scholar
  94. Xie J-W, Huang L-F, Hu W, He Y-B, Wong KP (2010) Analysis of the Main Nucleosides in Cordyceps Sinensis by LC/ESI-MS. Molecules 15:305–314PubMedPubMedCentralCrossRefGoogle Scholar
  95. Yalin W, Cuirong S, Yuanjiang P (2006) Studies on isolation and structural features of a polysaccharide from the mycelium of a Chinese edible fungus (Cordyceps sinensis). Carbohydr Polym 63:251–256CrossRefGoogle Scholar
  96. Yang F-Q, Ge L, Yong JWH, Tan SN, Li S-P (2009) Determination of nucleosides and nucleobases in different species of Cordyceps by capillary electrophoresis–mass spectrometry. J Pharm Biomed Anal 50:307–314PubMedCrossRefPubMedCentralGoogle Scholar
  97. Yang FQ, Guan J, Li SP (2007) Fast simultaneous determination of 14 nucleosides and nucleobases in cultured Cordyceps using ultra-performance liquid chromatography. Talanta 73:269–273PubMedCrossRefPubMedCentralGoogle Scholar
  98. Yang QZ, Yang J, Zhang CK (2006) Synthesis and properties of cordycepin intercalates of Mg–Al–nitrate layered double hydroxides. Int J Pharm 326:148–152PubMedCrossRefPubMedCentralGoogle Scholar
  99. Yang FQ, Li DQ, Feng K, Hu DJ, Li SP (2010) Determination of nucleotides, nucleosides and their transformationproducts in Cordyceps by ion-pairing reversed-phase liquid chromatography-mass spectrometry. J Chromatogr A.34:5501–5510.  https://doi.org/10.1016/j.chroma.2010.06.062.PubMedCrossRefPubMedCentralGoogle Scholar
  100. Yang X, Li Y, He Y, Li T, Wang W, Zhang J, Wei J, Deng Y, Lin R (2015) Cordycepin alleviates airway hyperreactivity in a murine model of asthma by attenuating the inflammatory process. Int Immunopharmacol 26:401–408PubMedCrossRefPubMedCentralGoogle Scholar
  101. Yao L-H, Li C-H, Yan W-W, Huang J-N, Liu W-X, Xiao P (2011) Cordycepin decreases activity of hippocampal CA1 pyramidal neuron through membrane hyperpolarization. Neurosci Lett 503:256–260PubMedCrossRefPubMedCentralGoogle Scholar
  102. Yao L-H, Meng W, Song R-F, Xiong Q-P, Sun W, Luo Z-Q, Yan W-W, Li Y-P, Liu X-P, Li H-H, Xiao P (2014) Modulation effects of cordycepin on the skeletal muscle contraction of toad gastrocnemius muscle. Eur J Pharmacol 726:9–15PubMedCrossRefPubMedCentralGoogle Scholar
  103. Yoshikawa N, Nakamura K, Yamaguchi Y, Kagota S, Shinozuka K, Kunitomo M (2004) Antitumor activity of cordycepin in mice. Clin Exp Pharmacol Physiol 31:S51–S53PubMedCrossRefPubMedCentralGoogle Scholar
  104. Yu R, Song L, Zhao Y, Bin W, Wang L, Zhang H (2004a) Isolation and biological properties of polysaccharide CPS-1 from cultured Cordyceps militaris. Fitoterapia 75:465–472PubMedCrossRefPubMedCentralGoogle Scholar
  105. Yu R, Wang L, Zhang H, Zhou C, Zhao Y (2004b) Isolation, purification and identi- fication of polysaccharides from cultured Cordyceps militaris. Fitoterapia 75:662–666PubMedCrossRefPubMedCentralGoogle Scholar
  106. Yun YH, Han SH, Lee SJ, Ko SK, Lee CK, Ha NJ, Kim KJ (2003) Anti-diabetic effects of CCCA, CMESS, and cordycepin from Cordyceps militaris and the immune responses in Streptozotocin-induced diabetic mice. Nat Prod Res 9:291–298Google Scholar
  107. Zhang DW, Deng H, Qi W, Zhao GY, Cao R (2015) Osteoprotective effect of cordycepin on estrogen deficiency-induced osteoporosis in vitro and in vivo. Biomed Res Int 2015:423869PubMedPubMedCentralGoogle Scholar
  108. Zhang Z, Tudi T, Liu Y, Zhou S, Feng N, Yang Y, Tang C, Tang Q, Zhang J (2016) Preparative isolation of cordycepin, N 6 -(2-hydroxyethyl)-adenosine and adenosine from Cordyceps militaris by macroporous resin and purification by recycling high-speed counter-current chromatography. Journal of Chromatography B 1033-1034:218–225CrossRefGoogle Scholar
  109. Zheng P, Xia Y, Xiao G, Xiong C, Hu X, Zhang S, Zheng H, Huang Y, Zhou Y, Wang S, Zhao GP (2012) Genome sequence of the insect pathogenic fungus Cordyceps militaris, a valued traditional Chinese medicine. Genome Biol 12(11):R116CrossRefGoogle Scholar
  110. Zheng ZL, Qiu XH, Han RC (2015) Identification of the genes involved in the fruiting body production and cordycepin formation of Cordyceps militaris fungus. Mycobiology 43:37–42PubMedPubMedCentralCrossRefGoogle Scholar
  111. Zhou X, Meyer CU, Schmidtke P, Zepp F (2002) Effect of cordycepin on interleukin-10 production of human peripheral blood mononuclear cells. Eur J Pharmacol 453:309–317PubMedCrossRefPubMedCentralGoogle Scholar
  112. Zhu JS, Halpern GM, Jones K (1998) The scientific rediscovery of an ancient Chinese herbal medicine: Cordyceps sinensis: part I. J Altern Complement Med 4:289–303PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Mohammad Soltani
    • 1
  • Roslinda Abd Malek
    • 1
  • Nagib A. Elmarzugi
    • 2
  • Mohamad Fawzi Mahomoodally
    • 3
  • Davin Uy
    • 4
  • Ong Mei Leng
    • 5
  • Hesham A. El-Enshasy
    • 6
    • 7
    • 8
    Email author
  1. 1.Institute of Bioproduct Development (IBD)Universiti Teknologi Malaysia (UTM)SkudaiMalaysia
  2. 2.Department of Industrial PharmacyFaculty of Pharmacy & Biotechnology Research CenterTripoliLibya
  3. 3.Department of Health Sciences, Faculty of ScienceUniversity of MauritiusRéduitMauritius
  4. 4.Research and Innovation Center, Tumnuptek, ChamkarmornPhnom PenhCambodia
  5. 5.Harita Go Green Sdn BhdJohor BahruMalaysia
  6. 6.Institute of Bioproduct DevelopmentUniversiti Teknologi MalaysiaJohor BahruMalaysia
  7. 7.School of Chemical Engineering, Faculty of EngineeringUniversiti Teknologi MalaysiaJohor BahruMalaysia
  8. 8.City of Scientific Research and Technology Application, New Burg Al ArabAlexandriaEgypt

Personalised recommendations