Black pepper (Piper nigrum L.) fruit extract ameliorates erectile dysfunction in alloxan-induced diabetic rats

<ns3:p> Background Diabetes mellitus (DM) is a chronic metabolic disorder frequently associated with male sexual and reproductive dysfunction, including erectile dysfunction (ED), reduced libido, and impaired spermatogenesis. Black pepper ( <ns3:italic>Piper nigrum</ns3:italic> L.) fruit extract has been reported to possess antidiabetic and reproductive benefits, yet its effect on DM-related ED remains underexplored. Objective To evaluate the effects of <ns3:italic>Piper nigrum</ns3:italic> fruit extract on erectile function, libido, sperm parameters, and testicular histology in alloxan-induced diabetic male rats. Methods Thirty male Sprague Dawley rats were divided into five groups: normal control, diabetic control, diabetic rats treated with black pepper extract (122.5 or 245 mg/kg BW), and diabetic rats treated with sildenafil citrate. Erectile function was assessed via penile reflexes, libido by mating behavior, sperm quality by concentration, motility, and morphology, and testicular histology by Leydig cell and spermatogonia counts. Data were analyzed using ANOVA with significance at p&lt;0.05. Results Alloxan-induced diabetic rats showed significant impairment in erectile function, libido, sperm quality, and testicular histology (p&lt;0.001 vs control). Black pepper extract at 122.5 mg/kg BW significantly improved total penile reflexes compared with diabetic controls (9.33±1.03 vs 6.00±1.26, p=0.02). Libido parameters including courtship latency (5.50±0.55 vs 21.00±9.47, p=0.013), mount latency (19.00±10.81 vs 37.17±6.31, p=0.009), and mount frequency (18.05±5.99 vs 7.17±1.83, p=0.002) were significantly improved. Sperm analysis revealed increases in sperm concentration (19.2±6.7 vs 12.6±1.3, though not significant, p=0.877), motility (31.8±23 vs 27±30, p=0.697), and normal morphology (40.9±7.8 vs 35±10.8, p=0.04). Testicular histology showed restoration of Leydig cell count (59.33±4.0 vs 30.50±3.86, p=0.035) and spermatogonia number (319.4±64.59 vs 491±37.0, p&lt;0.001). The 245 mg/kg BW dose primarily improved sperm concentration (62.95±29.4 vs 12.6±1.3, p=0.01) and motility (36.6±23 vs 27±30, p=0.436). Sildenafil citrate significantly enhanced most parameters compared with diabetic controls (p&lt;0.05). Conclusion <ns3:italic>Piper nigrum</ns3:italic> fruit extract ameliorates sexual dysfunction and reproductive impairment in alloxan-induced diabetic rats, particularly at 122.5 mg/kg BW, with significant improvements in erectile function, libido (p&lt;0.05), sperm quality (p≤0.04), and testicular histology (p=0.035). These findings suggest its potential as a natural therapeutic agent for DM-related male reproductive dysfunction. </ns3:p>