Cordycepin, a major bioactive component ofCordyceps militaris, ameliorates diabetes‐induced testicular damage through the Sirt1/Foxo3a pathway

Abstract

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.

Bibliometric and visual analysis of blood-testis barrier research

“…Toxicants in the environment, chemotherapeutic medications, heat, and illness disrupt Sertoli cell structure and function, causing damage to the BTB and a link to excessive ROS generation ( Agarwal et al, 2003 ). These health risks can be ameliorated via oral administration of some bioactive agents, including betaine ( Jiang et al, 2019 ), aucubin ( Ma et al, 2019b ), salidroside ( Jiang et al, 2020 ), paeonol ( Morsy et al, 2020 ), betulinic acid ( Lin et al, 2022 ), and cordycepin ( Huang et al, 2022 ). Ascorbic acid, a well-known ROS scavenger, may protect against BTB degradation by inhibiting oxidative stress ( Chen et al, 2018 ).…”

Hirsutella sinensis intensifies testicular function and spermatogenesis in male mice with high-fat diet-induced obesity

“…These results are partly supported by earlier published data showing that cordycepin, a bioactive ingredient of C. militaris, downregulated the protein expressions of cleaved caspase 3 and cleaved PARP, as detected by western blotting and immunohistology, in the testes of diabetic mice. 37 Further research focusing on HS treatment and the apoptotic pathway should be undertaken.…”

Diabetes and diabetic associative diseases: An overview of epigenetic regulations of TUG1

“…Diabetes can lead to testicular damage due to impaired blood flow and oxidative stress. Elevated blood sugar levels in diabetes contribute to inflammation and reduced function of the testes, potentially causing hormonal imbalances and reduced sperm production ( Abdel-Aziz et al, 2020 , Huang et al, 2022 , Thapa et al, 2022 ). Additionally, neuropathy and vascular complications associated with diabetes can further exacerbate testicular damage.…”