Complementary therapeutic actions of Shikonin and Indole propionic acid ameliorate diabetic infertility via distinct antioxidant and metabolic pathways
Year: 2025
Type: article
Abstract: OBJECTIVE: To evaluate the effect of Shikonin, a potent direct reactive oxygen species (ROS) scavenger, and Indole propionic acid (IPA), a microbiome-derived metabolite, on epididymis and sperm morphology and function in diabetic rats. DESIGN: A rat model of Type 2 diabetes mellitus (T2DM) was induced in male Wistar rats using a high-fat diet and streptozotocin (50 mg/kg). The animals were subsequently divided into seven groups: Control, T2DM, T2DM + IPA (50 mg/kg), T2DM + Shikonin (0.5 mg/kg), T2DM + Metformin (50 mg/kg), IPA-only, and Shikonin-only. Treatments were administered orally for 4 weeks. We assessed histological integrity, sperm motility, and viability (via computer-assisted sperm analysis), serum lipid profiles, epididymal antioxidant activity (superoxide dismutase, malondialdehyde, and catalase), and apoptotic marker (cytochrome C, caspase-9, and caspase-3) and metabolic signature (fibroblast growth factor 21 [FGF21]) expression via quantitative reverse transcription polymerase chain reaction. SUBJECTS: Male Wistar albino rats (n = 42, Age: 8-12 weeks old, 200 ± 2.4 g). INTERVENTION: Streptozotocin, Shikonin, Indole propionic acid. MAIN OUTCOME MEASURES: Type 2 diabetes mellitus profoundly impairs male fertility, with oxidative stress in the epididymis being a key driver of sperm damage. RESULTS: Streptozotocin-induced diabetic rats exhibited increased oxidative damage, characterized by an impaired antioxidant system, high expression of apoptotic markers, and reduced metabolic gene expression. These effects ultimately damaged epididymis tissue and resulted in poor sperm quality. Shikonin and IPA treatments significantly attenuated oxidative stress and apoptosis, restored antioxidant activity and lipid profiles, and improved sperm parameters. Both treatments enhanced metabolic balance, as indicated by improved FGF21 expression, and restored epididymal histoarchitecture. Shikonin was superior in improving the epididymal somatic index and sperm motility, whereas IPA was more effective in normalizing FGF21 expression and lipid profiles, highlighting its primary metabolic role. CONCLUSION: Our findings reveal that Shikonin and IPA protect against diabetic reproductive damage through complementary pathways. This work not only introduces promising natural therapeutic strategies but also provides a mechanistic framework for their combined or targeted use in managing diabetic infertility.
Source: F&S Science
Authors: Imran Tarique, Ali Haider, Fatima Nawazish
Institution: National University of Sciences and Technology
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,500
OpenAlex ID: W4416405112