Protective Effect of Cordycepin Against Cyclophosphamide-Induced Ovarian Damage in Rats via Antioxidant, Anti-Inflammatory and Antiapoptotic Mechanisms

Abstract Background Cyclophosphamide (CYC) is one of the most commonly used chemotherapy drugs, but it carries a high risk of damage to the ovaries. The current study aims to investigate the potential therapeutic effects of Cordycepin on cyclophosphamide (CYC)-induced ovarian damage by evaluating histological and biochemical parameters. Methods Forty female Wistar albino rats were randomly divided into four groups: Group 1 (Sham), Group 2 (CYC), Group 3 (CYC + 3 mg/kg cordycepin), and Group 4 (CYC + 10 mg/kg cordycepin). Cordycepin was administered orally by gavage for 10 consecutive days. On day 5, a single intraperitoneal dose of 150 mg/kg CYC was administered to groups 2,3 and 4. Ovarian damage and reserve were assessed using histological evaluation and serum/tissue biochemical markers. Results Cordycepin treatment significantly increased serum anti-Müllerian hormone and inhibin B levels while reducing ovarian histopathological damage scores ( p < 0.05). It also decreased malondialdehyde (MDA) levels and enhanced superoxide dismutase (SOD) activity and glutathione (GSH) levels ( p < 0.05). Elevated levels of phosphorylated nuclear factor-κB (phospho-NF-κB p65), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), γH2AX immunoreactivity, and TUNEL assay positivity observed in the CYC group were significantly reduced by cordycepin treatment ( p < 0.05). Conclusion Cordycepin exerts protective effects against CYC-induced ovarian toxicity through its antioxidant, anti-inflammatory, and antiapoptotic properties, improving both ovarian structure and function.