Retama raetam Extract for Testicular Health in Type 2 Diabetic Rats: Insight View on the Steroidogenesis, Antioxidants, and Molecular Docking Scores of Bioactive Compounds against Bax

Abstract

The exponential growth of obesity rates is a pressing issue, as it is now firmly established as a primary driver behind the development of metabolic disorders. Natural products are crucial in drug discovery, prompting an increasing need for further research on bioactive compounds to understand molecular and pharmacological mechanisms and expand available clinical treatments for various diseases. We set out to investigate the therapeutic potential of Retama raetam (RR) extract, a natural compound, in alleviating testicular degeneration and improving sperm quality and quantity in high-fat diet (HFD)-induced type 2 diabetes mellitus (T2DM) and streptozotocin (STZ)-induced type 2 diabetes mellitus. An eight-week high-fat diet (HFD) was administered to type 2 diabetic rats, and then a modest dose of 35 mg/kg of STZ was injected intraperitoneally. The experiment planned to assess the influence of RR extract on the steroidogenesis pathway. For twelve weeks, the rats were given medications orally. The testicular degeneration caused by HFD/STZ is shown by decreasing the accessory sexual glands while reducing the quality of sperm characters and testosterone levels with significantly increased pad fat and leptin levels. Furthermore, administration of RR extract effectively counteracted HFD/STZ-induced oxidation through enhancing the antioxidant status of the testicular tissue through significantly increased SOD and GSH accompanied by decreasing MDA. HFD/STZ rats showed decreased expression of CYP17, STAR, 3βHSD, and BCL2 genes, along with increased BAX gene expression. However, treatment with RR in HFD/STZ rats led to decreased BAX expression and increased expression of CYP17, STAR, 3βHSD, and BCL2 genes, indicating a restoration of gene expression values similar to the control group. The binding site of Bax showed a strong affinity for several bioactive compounds found in R. raetam. The findings from this study suggest that Retama raetam (RR) has the potential as a therapeutic adjunct for managing complications related to type 2 diabetes mellitus (T2DM). These findings afford credence to the idea that RR can be useful in treating infertility associated with type 2 diabetes.