Protection and Rehabilitation Effects of Cordyceps militaris Fruit Body Extract and Possible Roles of Cordycepin and Adenosine

Cordyceps militaris is a valued medicinal fungus in folk medicine in East Asia. It contains two major nucleosides, cordycepin and adenosine, which have been reported to have potential antineoplastic, antioxidant, and anti-inflammatory activities. This paper aimed to study the effect of C. militaris extract on the reproductive function of a mouse model, evaluating possible toxicity, androgenic activity, and protective and rehabilitative effects against damages caused by sodium valproate (VPA). There was no death and abnormalities observed in mice. Androgen activity was also shown in young male rats by an improvement in several sexual organs. The protective effect of C. militaris extract was explained by the gain of sexual organs’ weight, testosterone concentration, and seminiferous tubule size as well as the enhancement of sperm density, alive sperm percentage, and the progressive forward movement of sperm. The pregnancy rate of female rats paired with VPA-administered male rats (500 mg/kg/day) increased proportionally with the higher dose of C. militaris extract. In the rehabilitation study, an incline in the weight of the Cowper’s gland and glans (0.112 g/kg/day) and testicle and prostate (0.336 g/kg/day) as well as an improvement of the sperm forward progressive movement was observed. The percentage of unprogressive sperm and immotile sperm has reduced. These results suggest that C. militaris is a potential supplement to reduce the negative effects of VPA and improve reproductive function, in which the two major constituents cordycepin and adenosine may play an active role.