Effects of Black Pepper (Piper nigrum L.) Fruit Extract on Sexual Function, Hormonal Parameters, Sperm Parameters, Testicular Histology, and eNOS Expression in Alloxan-Induced Diabetic Rats

<ns3:p> Background Diabetes mellitus (DM) is often associated with male sexual and reproductive dysfunction, including erectile impairment, reduced libido, hormonal disturbances, and poor semen quality. Black pepper ( <ns3:italic>Piper nigrum</ns3:italic> L.) fruit extract has shown antidiabetic and reproductive benefits in experimental studies, but its role in diabetes-related sexual dysfunction remains unclear. Objective To evaluate the effects of black pepper fruit extract on hormonal, erectile, libido, sperm, histological, and molecular parameters in alloxan-induced diabetic male rats. Methods Thirty male Sprague Dawley rats were assigned to five groups: normal control, diabetic control, diabetic rats treated with black pepper extract at 122.5 or 245 mg/kg body weight (BW) for 8 consecutive days, and diabetic rats treated with sildenafil citrate 1 mg/kg BW. Outcomes included intratesticular testosterone (ITT), erectile parameters (quick flip, long flip, erection, total penile reflexes [TPR]), libido parameters (courtship latency [CL], mount latency [ML], mount frequency [MF]), sperm parameters (concentration, progressive motility, normal morphology), Leydig cell and spermatocyte counts, and eNOS mRNA expression. Data were analyzed using the Kruskal-Wallis test followed by Dunn’s post hoc test. Results Compared with diabetic controls, the 122.5 mg/kg BW black pepper group significantly improved TPR, CL, ML, and MF. The 245 mg/kg BW group significantly improved ITT, sperm concentration, and normal sperm morphology. Both black pepper doses increased Leydig cell counts. Sildenafil significantly improved TPR, sperm concentration, progressive motility, and normal morphology. eNOS mRNA expression was higher in all treatment groups than in diabetic controls. Conclusion Black pepper fruit extract showed dose-dependent effects in alloxan-induced diabetic rats. The lower dose was more beneficial for erectile and libido-related parameters, whereas the higher dose had greater effects on ITT and selected sperm outcomes. These findings support its potential as a preclinical candidate for diabetic male sexual and reproductive dysfunction. </ns3:p>