Extraction, Characterization, and Biological Evaluation of Atranorin Against Diabetes-Induced Reproductive Dysfunction Through Modulation of Oxidative Stress, Inflammatory Pathways and Key Reproductive Enzymes

Male fertility is declining worldwide, with notable reductions in sperm counts, emphasizing the need for new therapeutic interventions. Atranorin (ATR), a lichen-derived secondary metabolite, exhibits strong antioxidant and anti-inflammatory activities. This study assessed the protective effects of ATR on type 1 diabetes (T1D)-induced reproductive dysfunction in rats. T1D was induced in male Wistar rats via a single intraperitoneal injection of alloxan at 150 mg/kg body weight (bw). ATR significantly ameliorated T1D-related reproductive damage. At 170 mg/kg bw, ATR reduced hyperglycemia by 66% and attenuated seminal inflammation, decreasing leukocyte infiltration (−51%) and myeloperoxidase (MPO) activity (−68%). Oxidative balance improved, as evidenced by increased total antioxidant status (TAS) (+203%) and decreased thiobarbituric acid reactive substances (TBARS) (−73%), hydrogen peroxide (H₂O₂) (−45%), and total oxidant status (TOS) (−70%). Steroidogenesis was restored through enhanced 3β-hydroxysteroid dehydrogenase (3β-HSD) (+65%) and 17β-hydroxysteroid dehydrogenase (17β-HSD) (+102%) activities, resulting in a 90% recovery of testosterone levels. Seminal plasma function improved, with increased fructose levels (+71%), normalized pH (7.4), and enhanced hyaluronidase (HYAL) (+71%), adenosine triphosphatase (ATPase) (+71%), and prostatic acid phosphatase (PAP) (+79%) activities. Fertility biomarkers, such as adenosine deaminase (ADA) (+148%) and lactate dehydrogenase-C4 (LDH-C4) (+62%), increased, and essential minerals Zn²⁺ (+72%), Ca²⁺ (+96%), Mg²⁺ (+84%), and Se (+57%) were restored. Consequently, sperm density (+87%), viability (+69%), and motility (+189%) improved, while abnormalities declined (−46%). Histological findings confirmed the restoration of spermatogenesis and epididymal maturation. ATR effectively counteracts diabetes-induced reproductive dysfunction by reducing oxidative and inflammatory stress while improving hormonal and seminal parameters.