Sorghum bicolor polyphenol-rich supplement ameliorates chronic stress exacerbated hypothalamic-pituitary-testicular axis dysregulation in diabetic rats through suppression of inflammation and apoptosis

Abstract

Diabetes mellitus, characterized by prolonged elevated blood glucose levels, is often associated with dysfunction in the hypothalamic-pituitary-testicular axis. Sorghum bicolor leaf sheath is known for its high antioxidant content and therapeutic benefits. This study investigated the effects of a S. bicolor polyphenol-rich supplement (SBPS) on testicular dysfunction in diabetic rats exposed to chronic unpredictable mild stress (CUMS). Male Wistar rats divided into five groups (n = 7) were fed with high fat diet and injected streptozotocin (35 mg/kg) intraperitoneally. Groups 1 was non-diabetic control, 2 (HFD/STZ), and 3 (HFD/STZ/CUMS) were treated with vehicle. Groups 4–6 (HFD/STZ/CUMS) orally treated for 28 days with SBPS (200 mg/kg), metformin (250 mg/kg) and SBPS+metformin, respectively. Seminal sperm parameters, plasma reproductive hormones, brain hypothalamic and testicular inflammatory, oxidative and apoptosis markers were analysed. Oral administration of SBPS significantly reduced FBS in diabetic rats. Sperm count, plasma and testicular testosterone were significantly increased in diabetic-rats treated with SBPS. Chronic stress-exacerbated increase in diabetic hypothalamic and testicular levels of TNF-α, IL-1β, myeloperoxidase, arginase were significantly decreased in rats treated with SBPS, metformin and SBPS+metformin. Testicular increases in apoptotic markers (caspase-3, caspase-9) and NF-κB, along with reduced Nrf2 levels, were significantly reversed by SBPS, metformin, and their combination. The findings suggest that SBPS ameliorates stress-exacerbated diabetes-induced testicular dysfunction. This is achieved through the suppression of oxidative stress, inflammation, and apoptosis via modulation of Nrf2 and NF-κB pathways. These results highlight the potential of SBPS as a therapeutic agent and its combination with metformin in managing diabetes-related reproductive dysfunction.