Diabetes-induced male dysfunction is considered as a worldwide challenge, and testicular damage mainly caused by oxidative stress is its most common manifestation.
Cordycepin, a natural
antioxidant, has been used in the treatment of
diabetic complications. However, the protective action and underlying mechanism of
cordycepin on hyperglycaemia-induced testicular damage are unclear. This study aimed to investigate the protective effects and molecular mechanisms of
cordycepin against diabetes-induced testicular damage. The
type 2 diabetes model was established in C57BL/6 male mice via high-fat diet for 4 weeks and injected intraperitoneally with 50 mg/kg/day
streptozotocin for five consecutive days. Then mice were treated with
cordycepin (10 and 20 mg/kg, respectively) for 8 weeks. At the end of experiment, biochemical indicators, microstructure of testicular tissue, sperm morphology, TUNEL staining and
protein expressions were evaluated. In the present study,
cordycepin alleviated the testicular damage, restored disruption of the blood-testis barrier, and improved spermatogenic function via the antiapoptotic and
antioxidant capacity. Mechanistically,
cordycepin significantly enhanced
SIRT1 expression and triggered the activity of Foxo3a, further to induce the expression of its downstream
antioxidant enzymes, including
Mn-SOD and CAT. These findings indicated that
cordycepin could improve hyperglycaemia-induced testicular damage by regulating downstream
antioxidant enzymes activity through the
SIRT1/Foxo3a signalling pathway.