Ophiocordyceps sinensis e i suoi effetti di controllo epigenetico dell’infiammazione

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.

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