Shikonin mitigates diabetic testicular dysfunction by improving oxidative, apoptotic, and metabolic functions in rats

Type 2 diabetes mellitus (T2DM) is a health concern worldwide, leading to high blood sugar levels and adversely affects various organ systems, including reproductive organs. The present study was conducted by the need to address the fact that T2DM exerts deleterious effects on male fertility via decreasing the circulating testosterone levels and increasing oxidative stress, apoptosis, and metabolic dysregulation in germ cells. The study purposes to explore the protective effect of Shikonin, a bioactive compound, on T2DM-induced reproductive damage. A high-fat diet along with streptozotocin (50 mg/kg) was administered for the induction of T2DM in male albino rats. The five experimental groups included, control, T2DM, T2DM+Shikonin (0.5 mg/kg), Only Shikonin (0.5 mg/kg), and T2DM+Metformin (50 mg/kg) were established for 4 weeks. Notably, Shikonin-treated diabetic rats exhibited significantly (p < 0.0001) increased body weight, Gonadosomatic index (GSI), Testosterone, and antioxidant response reflected in the significant increase (P < 0.05) in superoxide dismutase and catalase levels, while decreasing malondialdehyde. Histological analysis revealed improved testicular health in T2DM rats treated with Shikonin compared to those treated with Metformin. Shikonin treatment led to a further reduction in pro-apoptotic signaling (cytochrome c, caspase 9, and caspase 3) and improved metabolic disturbances by modulating levels of Fibroblast Growth Factor21 (FGF21) and Lactate Dehydrogenase C (LDHC) in T2DM rats. Compared with metformin, Shikonin showed the potential to offer more protective effects on male reproductive health while effectively managing diabetes, hence revealing its dual role. These findings disclose the significant (P < 0.05) potential of Shikonin in protecting reproductive health against T2DM-induced oxidative stress and apoptosis, hence giving a promising avenue for the therapeutic management of diabetes-induced reproductive complications. The study emphasizes the necessity for future human trials to assess the long-term effects and dosing of Shikonin as a therapeutic option for managing T2DM and its reproductive complications.