Zingerone ameliorates diabetes-induced male reproductive damage by activating Sirt1/Nrf2/HO-1 pathway

Male diabetes mellitus is a pervasive metabolic disorder that severely compromises reproductive health, leading to infertility. This damage often manifests as impaired sperm quality, reduced testosterone levels, and increased oxidative stress in testicular tissue. Current therapeutic strategies for diabetes-induced male infertility are often insufficient or come with side effects, highlighting a critical need for novel interventions. Natural antioxidants, such as zingerone, are increasingly explored for their potential to mitigate oxidative damage and modulate key cellular pathways involved in reproductive function.

Researchers investigated zingerone's effects on diabetes-induced reproductive damage in male rats. Seventy-five male Sprague Dawley rats (250-300 g, 10-12 weeks old) were divided into six groups: control, zingerone (50 mg/kg), zingerone (100 mg/kg), diabetes, diabetes with zingerone (50 mg/kg), and diabetes with zingerone (100 mg/kg). Diabetes was induced via a single intraperitoneal injection of 55 mg/kg streptozotocin. Zingerone was administered daily by oral gavage for 8 weeks. Primary endpoints included analysis of the Sirt1/Nrf2/HO-1 signaling pathway, Bax/Bcl-2 apoptosis ratio, sperm quality, and histopathological changes in testicular tissue.

Zingerone significantly reversed several diabetes-induced reproductive impairments. It reduced blood glucose levels, decreased malondialdehyde (MDA) levels (a marker of oxidative stress), and lowered the pro-apoptotic Bax/Bcl-2 ratio. Concurrently, zingerone markedly enhanced body weight, increased testosterone levels, and boosted antioxidant defenses by elevating glutathione (GSH) content and the activity of GSH-Px and CAT enzymes. Furthermore, zingerone significantly upregulated the expression of protective proteins: Sirt1, Nrf2, and HO-1. Histopathological examination revealed improved testicular architecture and spermatological parameters in diabetic rats treated with zingerone. The 100 mg/kg dose of zingerone consistently demonstrated superior efficacy across most measured parameters. > Zingerone treatment, particularly at 100 mg/kg, significantly improved sperm quality and restored testosterone levels in diabetic rats, alongside robust activation of the Sirt1/Nrf2/HO-1 antioxidant pathway.