Il fungo caterpillar Ophiocordyceps sinensis è un fungo parassita di insetti del genere Thitarodes (Hepialus armoricanus) che vivono in ecosistemi dell’altopiano Tibetano e dell’Himalaya ad altezze tra I 3300 to 5000 m slm, oltre la linea degli alberi. Ha un corpo fruttifero a forma di mazza la cui raccolta e utilizzo risalgono a oltre un migliaio di anni in Tibet, anche se sono state  ritrovate testimonianze scritte in tempi antecedenti in un testo scritto da Nyamnyi Dorje (1439 to 1475), “An Ocean of Aphrodisiacal Qualities—A special work on Yartsa Gunbu”. (1)

Nella medicina tradizionale cinese (TCM), il Cordyceps sinensis è comunemente conosciuto come “dong chong xia cao” che significa  “insetto d’inverno, pianta d’estate” che è la traduzione letterale del suo nome tibetano “Yartsa Gunbu”, ed è riconosciuto come uno dei tonici più famosi per secoli. In Giappone è chiamato tōchūkaso (2-4). Il valore medicinale del Cordyceps sinensis è stato riconosciuto per migliaia di anni in Cina e in Oriente in generale. Il folklore orientale declama la sua potenza, la sua capacità di rinforzare l’organismo e di conferire resistenza e volontà. In TCM Cordyceps sinensis sostiene il ruolo dei reni di conservazione dell’energia vitale; aiuta a recuperare dopo la malattia dando forza sia al corpo che alla mente. È consigliato per i dolori, per i problemi di reni e di polmoni, dove è usato anche per molte patologie delle vie respiratorie come la tosse, il muco, la mancanza di respiro, le problematiche bronchiali, la BPCO e l’asma (5-7). La ricerca scientifica occidentale ha evidenziato un effetto protettivo sia a livello cardiovascolare (21-22) che epatico (23-27). esercita una notevole azione potenziante sulle funzioni sessuali migiorando la libido e la fertilità sia nel maschio che nella femmina (28-40). È utile per migliorare la performance fisica degli atleti (41-42) e, nell’anziano, aiuta a ridurre le sintomatologie legate all’invecchiamento (43-47); studi recenti dimostrano che ha effetti neuroprotettivi sia a livello funzionale che lesionale (48-53).

Può essere considerato un adattogeno che esercita i suoi effetti principalmente a livello epigenetico.

La cordicepina è il principale composto bioattivo studiato contenuto nel Cordyceps sinensis. Si tratta di un’adenosina modificata (3′-deossiadenosina), con un ampio spettro di attività biologiche, anti-proliferative, pro-apoptotiche e anti-infiammatorie.

La cordicepina deve entrare nella cellula utilizzando i trasportatori dell’adenosina ed essere fosforilata per influenzare la risposta infiammatoria.

Con il suo utilizzo è stata notata una forte inibizione della sintesi proteica, che correla con l’inibizione della cascata di segnale di mTOR (target della ripamicina), con riduzione dei livelli di Akt chinasi e della fosforilazione della 4E-binding protein (4EBP).

La cordicepina inoltre riduce la lunghezza della coda di poli-A degli mRNA, con alcuni mRNA più sensibili di altri. Ciò che è  interessante è che la cordicepina inibisce l’espressione, indotta da citochine, degli mRNA per mediatori dell’infiammazione senza alterare l’espressione degli mRNA costitutivi. Il trattamento con cordicepina ha come effetto, oltre alla riduzione della  lunghezza della coda di poli-A, anche una riduzione dell’efficienza della terminazione dei trascritti degli mRNA infiammatori. (54-55)

Le proprietà anti-infiammatorie del Cordyceps sinensis sono state attribuite anche alla sua capacità di inibire sia l’assemblaggio che l’attivazione dell’inflammasoma, evitando la produzione delle citochine pro-infiammatorie IL-1 beta e IL-18. Inoltre, in modelli animali di osteoartrite la cordicepina  somministrata per via orale ha dimostrato effetti analgesici e condroprotettivi, con attività di modificazione sinoviale e di rimodellamento osseo (56).

Anche se sono necessari ulteriori studi, i risultati delle ricerche forniscono un razionale per l’uso del Cordyceps sinensis e della cordicepina come nuovo approccio al trattamento di condizioni infiammatorie.

 

Bibliografia

  1. D. Caterpillar Fungus (Ophiocordyceps sinensis) Production and Sustainability on the Tibetan Plateau and in the Himalayas. Asian Medicine 5 (2009) 291–316).
  2. 1997. An ancient Chinese secret promotes longevity and endurance. Healthy and Natural Journal, 3(3): 90-93.
  3. Shrestha and J.-M. Sung, “Notes on Cordyceps species collected from the central region of Nepal,” Mycobiology, vol. 33, no. 4, pp. 235–239, 2005. 

  4. Winkler D. The wild life of Yartsa Gunbu (Ophiocordyceps sinensis) on the Tibetan Plateau. Fungi (2017)Vol. 10:1
  5. Jia-Shi Zu, Georges M. Halpern, Kennet Jones. The scientific rediscovery of an ancient Chinese herbal medicine: Cordyceps sinensis – part I. The journal of Alternative and Complementary Medicine (1998) Vol.4(3): 289-303
  6. Zhu, Jia-Shi, Georges M. Halpern, and Kenneth Jones, 1998 [2]. The Scientific Rediscovery of an Ancient Chinese Herbal Medicine: Cordyceps sinensis Part II. Journal of Alternative and Complementary Medicine Vol 4, Num 4, pp  429-457
  7. Rakesh K Joshi. Phytochemical and medicinal aspect of Cordyceps sinensis (Berk.): A review. Journal of Medicinal Plants Studies 2016; 4(1): 65-67
  8. Zhao-Long W, Xiao-Xia W, Wei-Ying C. Inhibitory effect of Cordyceps sinensis and Cordyceps militaris on human glomerular mesangial cell proliferation induced by native LDL. Cell Biochem Funct. 2000 Jun;18(2):93-7.
  9. Lu L. Zhongguo Zhong Xi Yi Jie He Za Zhi. Study on effect of Cordyceps sinensis and artemisinin in preventing recurrence of lupus nephritis. Alternative Medicine Review (2002). Vol 22:169-171
  10. Fang Zhong, Xia Liu, Qiao Zhou, Xu Hao, Ying Lu, Shanmai Guo, Weiming Wang, Donghai Lin, and Nan Chen.1H NMR spectroscopy analysis of metabolites in the kidneys provides new insight into pathophysiological mechanisms: applications for treatment with Cordyceps sinensis. Nephrol. Dial. Transplant. (2011) doi: 10.1093/ndt/gfr368
  11. Hua-Pin Wang, Ching-Wen Liu, Hsueh-Wen Chang, Jen-Wei Tsai, Ya-Zhu Sung, Li-Ching Chang. Cordyceps sinensis protects against renal ischemia/reperfusion injury in rats Molecular Biology Reports
. 2013, Vol 40(3):2347–2355
  12. Kai Zhao, Yongjian Li, Hong Zhang. Role of Dongchongxiacao (Cordyceps) in prevention of contrast-in- duced nephropathy in patients with stable angina pectoris. J Tradit Chin Med (2013); 33(3): 283-286
  13. Sung-Hsun Yu, Navneet Kumar Dubey, Wei-Shan Li, Ming-Che Liu, Han-Sun Chiang, Sy-Jye Leu, Ying-Hua Shieh, Feng-Chou Tsai, Win-Ping Deng. Cordyceps militaris Treatment Preserves Renal Function in Type 2 Diabetic Nephropathy Mice. PLoS One.2016 Nov 10;11(11):e0166342. doi: 10.1371/journal.pone.0166342. eCollection 2016
  14. Yue GG, Lau CB, Fung KP, Leung PC, Ko WH Effects of Cordyceps sinensis, Cordyceps militaris and their isolated compounds on ion transport in Calu-3 human airway epithelial cells. J Ethnopharmacol (2008) 117:92–101
  15. SJ Wang, W Bai, CL Wang, and Z Dai. Effects of cordyceps sinensis on bleomycin-induced pulmonary fibrosis in mice. Zhongguo Zhong Yao Za Zhi, 2007; 32(24): 2623-7.
  16. Eliza L.Y. Wong, Rita Yn Tz Sung, Ting Fan Leung, Yeuk Oi Wong, Albert, Kam Lau Cheung, Chun Kwok Wong, Tai Fai Fok, and Ping Chung Leung. Randomized, Double-Blind, Placebo-Controlled Trial of Herbal Therapy for Children with Asthma. The Journal of Alternative and Complementary Medicine (2009) Vol.15(10):1091–1097

  17. W Sun, J Yu, YM Shi, H Zhang, Y Wang, and BB Wu. Effects of Cordyceps extract on cytokines and transcription factors in peripheral blood mononuclear cells of asthmatic children during remission stage. Zhong Xi Yi Jie He Xue Bao (2010); 8(4): 341-6.
  18. Mrinalini Singh, Rajkumar Tulsawani, Praveen Koganti, Amitabh Chauhan, Manimaran Manickam, and Kshipra Misra. Cordyceps sinensis Increases Hypoxia Tolerance by Inducing Heme Oxygenase-1 and Metallothionein via Nrf2 Activation in Human Lung Epithelial Cells. BioMed Research International
Volume 2013, Article ID 569206, 13 pages http://dx.doi.org/10.1155/2013/569206
  19. Tianzhu Z, Shihai Y, Juan D The effects of cordycepin on ovalbumin-induced allergic inflammation by strengthening Treg response and suppressing Th17 responses in ovalbumin- sensitized mice. Inflammation (2015) 38:1036–1043 

  20. Ailing LiuJinxiang Wu,  Aijun Li, Wenxiang BiTian LiuLiuzhao CaoYahui Liu, and  Liang Dong. The inhibitory mechanism of Cordyceps sinensis on cigarette smoke extract-induced senescence in human bronchial epithelial cells. Int J Chron Obstruct Pulmon Dis
  21. Mei QB, Tao JY, Gao SB, Xu GC, Chen LM, Su JK
. Antiarrhythmic effects of Cordyceps sinensis (Berk.) Sacc. China Journal of Chinese Materia Medica 1989, 14(10):616-8, 640
  22. Xiao-Feng Yan, Zhong-Miao Zhang, Hong-Yi Yao, Yan Guan, Jian-Ping Zhu, Lin-Hui Zhang, Yong-Liang Jia, Ru-Wei Wang Cardiovascular Protection and Antioxidant Activity of the Extracts from the Mycelia of Cordyceps Sinensis Act Partially Via Adenosine Receptors. Phytother Res.2013 Nov;27(11):1597-604.
  23. Kazuki Nakamura, Yu Yamaguchi, Satomi Kagota, Kazumasa Shinozuka and Masaru Kunitomo. Activation of in vivo Kupffer cell function by oral administration of Cordyceps sinensis in rats, Jpn J Pharmacol. (1999) Vol.79: 505-508
  24. Yu-Kan Liu, Wei Shen. Inhibitive effect of cordyceps sinensis on experimental hepatic fibrosis and its possible mechanism. World J Gastroenterol 2003;9(3):529-533
  25. Wang-Sheng Ko, Shih-Lan Hsu, Charng-Cherng Chyau, Kuan-Chou Chen, Robert Y. Peng. Compound Cordyceps TCM-700C exhibits potent hepatoprotective capability in animal model. Fitoterapia (2010); 81: 1–7
  26. Gong HY, Wang KQ, Tang SG, Hunan Yi Ke Da Xue Xue Bao, Hunan Yike, Daxue Xuebao. Effects of cordyceps sinensis on T lymphocyte subsets and hepatofibrosis in patients with chronic hepatitis B. Bulletin Of Hunan Medical University [Hunan Yi Ke Da Xue Xue Bao], ISSN: 1000-5625, 2000 Jun 28; Vol. 25 (3), pp. 248-50;
  27. B. Ng, H. X. Wang. Pharmacological actions of Cordyceps, a prized folk medicine. Journal of Pharmacy and Pharmacology (2005) Vol. 57(12): 1509–1519
  28. Seu-MeiWang , Li-JenLee, Wan-WanLin, Chun-MinChang. Effects of a water-soluble extract of Cordyceps sinensis on steroidogenesis and capsular morphology of lipid droplets in cultured rat adrenocortical cells. Journal of Cellular Biochemistry (1998) vol. 69(4):483-489.
  29. Bu Miin Huang, Yu Ming Chuang, Chieu Fu Chen, and Sew Fen Leu. Effect of extracted Cordyceps sinensis on steroidogenesis in MA-10 Mouse Leydig tumor cells. Biol.Pharm.Bull (2000) Vol.23(12):1532-1535.
  30. Bu-Miin Huang, Sy-Yeuan Ju, Ching-Shyi Wu, Woei-Jer Chuang, Chia-Chin Sheu, and Sew-Fen Leu. Cordyceps sinensis and Its Fractions Stimulate MA-10 Mouse Leydig Tumor Cell Steroidogenesis. Journal of Andrology (2001), Vol. 22(5):831–837
  31. Bu-Miin Huang,Kuei-Yang Hsiao, Pei-Chin Chuang, Meng-Hsing Wu,Hsien-An Pan, and Shaw-Jenq Tsai. Upregulation of Steroidogenic Enzymes and Ovarian 17 -Estradiol in Human Granulosa-Lutein Cells by Cordyceps sinensis Mycelium. Biology Of Reproduction (2004) 70, 1358–1364
  32. Wen-Hung Lin, Ming-Ta Tsai
, Yuh-Shuen Chen
, Rolis Chien-Wei Hou, Hsiao-Fang Hung, Ching-Hsiao Li and Hsin-Kai Wang, Min-Nan Lai
, and Kee-Ching G. Jeng
. Improvement of Sperm Production in Subfertile Boars by Cordyceps militaris Supplement. The American Journal of Chinese Medicine (2007) Vol. 35(4): 631–641
  33. L. Wong, E. Cheung So, C. C. Chen and R. S. C. Wu, and B.-M. Huang. Regulation of Steroidogenesis by Cordyceps sinensis Mycelium Extracted Fractions with (hCG) Treatment in Mouse Leydig Cells. Archives of Andrology (2007), Vol.53:75–77,
  34. Ying Chang, Kee-Ching Jeng, Kuei-Fen Huang, Ying-Chung Lee, Chien-Wei Hou, Kuan-Hao Chen, Fu-Yen Cheng, Jiunn-Wang Liao, and Yuh-Shuen Chen. Effect of Cordyceps Militaris Supplementation on Sperm Production, Sperm Motility and Hormones in Sprague-Dawley Rats. The American Journal of Chinese Medicine (2008), Vol. 36, No. 5, 849–859
  35. Sew-Fen Leu, Song Ling Poon, Hsiang-Yin Pao, and Bu-Miin Huang
  36. The in Vivo and in Vitro Stimulatory Effects of Cordycepin on Mouse Leydig Cell Steroidogenesis. Biotechnology, and Biochemistry (2011), 75:4, 723-731
  37. Pao HY, Pan BS, Leu SF, Huang BM.
Cordycepin stimulated steroidogenesis in MA-10 mouse Leydig tumor cells through the protein kinase C Pathway. J Agric Food Chem. 2012 May 16;60(19):4905-13
  38. Sohn SH, Lee SC, Hwang SY, Kim SW, Kim IW, Ye MB, Kim SK. Effect of long-term administration of cordycepin from Cordyceps militaris on testicular function in middle-aged rats. Planta Med. 2012 Oct;78(15):1620-5
  39. Kanitta Jiraungkoorskul and Wannee Jiraungkoorskul. Review of Naturopathy of Medical Mushroom, Ophiocordyceps Sinensis, in Sexual Dysfunction. Pharmacogn Rev. 2016 Jan-Jun; 10(19): 1–5
  40. Yung-Chia Chen, Ying-Hui Chen, Bo-Syong Pan, Ming-Min Chang, Bu-Miin Huang. Functional study of Cordyceps sinensis and cordycepin in male reproduction: A review. Journal of Food and Drug Analysis. (2017), 25: 197-205
  41. Rajesh Kumar, PS Negi, Bhagwat Singh, Govindasamy Ilavazhagan, Kalpana Bhargava, Niroj Kumar Sethy. Cordyceps sinensis promotes exercise endurance capacity of rats by activating skeletal muscle metabolic regulation. Journal of ethnopharmacology (2011); 136: 260-266
  42. Paola Rossi, Daniela Buonocore, Elisa Altobelli, Federico Brandalise, Valentina Cesaroni, Davide Iozzi, Elena Savino, and Fulvio Marzatico. Improving Training Condition Assessment in Endurance Cyclists: Effects of Ganoderma lucidum and Ophiocordyceps sinensis Dietary Supplementation. Evidence-Based Complementary and Alternative Medicine 2014, Article ID 979613, 11 pages
  43. Zhang, Z.H.W., Liao, S., Li, J., Lei, L., Lui, J., Leng, F., Gong, W., Zhang, H., Wan, L., Wu, R., Li, S., Luo, H., Zhu, F., 1995. Clinical and laboratory studies of JinShuiBao in scavenging oxygen free radi- cals in elderly senescent XuZheng patients. Journal of Administration Traditional Chinese Medicine (1995), 5.
  44. Nam Sook Park, Kwang Sik Lee, Hung Dae Sohn, Do Hoon Kim, Sang Mong Lee, Eunju Park, Iksoo Kim, Yeon Ho Je, Byung Rae Jin. Molecular cloning, expression, and characterization of the Cu,Zn superoxide dismutase (SOD1) gene from the entomopathogenic fungus Cordyceps militaris. Mycologia, 97(1), 2005, pp. 130–138.

  45. Zun-sheng Wang, Yu-xiang Gu, Qin-sheng Yuan.Effect of Nutrition Factors on the Synthesis of Superoxide Dismutase, Catalase, and Membrane Lipid Peroxide Levels in Cordyceps militaris Mycelium. Current Microbiology (2006) Vol. 52: 74–79

  46. Deng-Bo Ji, Jia Ye, Chang-Ling Li, Yu-Hua Wang, Jiong Zhao and Shao-Qing Cai. Antiaging Effect of Cordyceps sinensis Extract. Phytother. Res. (2009) 23, 116–122 

  47. WC Wong, JY Wu, and IF Benzie Photoprotective potential of Cordyceps polysaccharides against ultraviolet B radiation-induced DNA damage to human skin cells. 
Br J Dermatol, (2011); 164(5): 980-6.
  48. In Koo Hwang, Soon Sung Lim, Ki-Yeon Yoo, Yeon Sil Lee, Ho Gyoung Kim, Il-Jun Kang, Hyung Joo Kwon, Jinseu Park, Soo Young Choi, Moo-Ho Won. A Phytochemically Characterized Extract of Cordyceps militaris and Cordycepin Protect Hippocampal Neurons from Ischemic Injury in Gerbils. PlantaMed2008;74:114–119
  49. Bombi Lee, Jongbong Park, Jinhee Park, Hyun-Jae Shin, Sunoh Kwon, Mijung Yeom, Bongjun Sur, Sunghun Kim, Myunghwan Kim, Hyejung Lee, Suk Hoo Yoon, Dae-Hyun Hahm. Cordyceps Militaris improves neurite outgrowth in Neuro2A cells and reverses memory impairment in rats. Food Science and Biotechnology
(2011), Vol. 20(6): 1599-1608
  50. Li Z, Zhang Z, Zhang J, Jia J, Ding J, Luo R, Liu Z.Cordyceps militaris extract attenuates D-galactose-induced memory impairment in mice. J Med Food. (2012);15(12):1057-63.
  51. Neeranjini Nallathamby, Lee Guan-Serm, Sharmili Vidyadaran, Sri Nurestri Abd Malek, Jegadeesh Raman, and Vikineswary Sabaratnam. Ergosterol of Cordyceps militaris Attenuates LPS Induced Inflammation in BV2 Microglia Cells. Natural Product Communications (2015) Vol. 10 (6): 885-886.
  52. Cheng-Han Tsai, Yue-Horng Yen, John Po-Wen Yang
. Finding of polysaccharide-peptide complexes in Cordyceps militaris and evaluation of its acetylcholinesterase inhibition activity. Journal of Food and Drug Analysis (2015); 23: 63-70
  53. H. Quyen, T.P.H. Yen, V.T. Xuyen, D.M. Hiep, T.B. Nguyen, P.N.D. Hoang. Study on the Ability of Extracts from Cordyceps Spp. Biomass to Prevent Long-Term Memory Impairment in Mice by Morris Water Maze. Journal of Agricultural Technology 2016 Vol. 12(7.2):2171-2180
  54. Wong, Ying Ying, et al. “Cordycepin inhibits protein synthesis and cell adhesion through effects on signal transduction.” Journal of Biological Chemistry 285.4 (2010): 2610-2621.
  55. Kondrashov, Alexander, et al. “Inhibition of polyadenylation reduces inflammatory gene induction.” Rna 18.12 (2012): 2236-2250.
  56. Ashraf, S., et al. “OP0183 Cordycepin, a novel compound, reduces knee joint pathology and pain in the monosodium iodoacetate (MIA) rat model of osteoarthritis.” (2017): 127-128.

 

Share This