Therapeutic Potential of <i>Cucurbita maxima</i> Duch. Seed Extract in Ameliorating Nonylphenol‐Induced Reproductive Toxicity in Male Mice: In‐Vivo and In‐Silico Approaches

Nonylphenol (NP) is an environmental contaminant known for its endocrine-disrupting properties, which can lead to male infertility. This study investigates the therapeutic potential of Cucurbita maxima Duch. seed extract (CMSE) in ameliorating NP-induced reproductive toxicity in male mice. Gas chromatography-mass spectrometry was used to identify the bioactive non-polar compounds of CMSE responsible for its activity. The binding affinity of these compounds with endothelial nitric oxide synthase, the primary neurotransmitter that triggers penile erection through the nitric oxide (NO)-cyclic guanosine monophosphate pathway using AutoDock Vina was investigated. Adult male mice were divided into six groups (n = 8) and infertility was induced by administering NP (50 mg/kg b.wt.) orally with olive oil for 35 days. Two doses of CMSE (250 and 500 mg/kg b.wt.) were administered, and blood samples were collected for serum NO analysis. Different sexual activities and fertility study was also done to investigate the reproductive performance. The results showed that NP significantly decreased serum NO levels, sexual activity and reproductive performance of mice whereas CMSE helped to mitigate these negative effects.