Abstract
BACKGROUND: Varicocele is a major male infertility issue, and Malva sylvestris shows promise as a treatment due to its antioxidant properties. The present study evaluated the protective effects of Malva sylvestris on testicular health, sperm quality, and oxidative stress-related gene expression. Adult male Wistar rats were randomly assigned into five groups (n = 8): the control group, the varicocele model group, the varicocele group with partial occlusion of the left renal vein treated with 750 or 1500 mg/kg Malva sylvestris for 21 days, and a surgical sham group. The epididymal content and Histological analyses of animals testicular tissue were examined to evaluate fertility parameters, and qRT-PCR was employed to determine the expression of SIRT1, FOXO1, NRF2, NF-κB, and TGF-β genes. RESULTS: Varicocele leads to the induction of apoptosis, the occurrence of DNA damage, a reduction in SIRT1 and FOXO1, and an increase in NRF2, TGF-β, and NF-κB gene expression. According to Histological morphometric analysis, treatment with Malva sylvestris showed the increased thickness of Mean Seminiferous Tubule Diameter and Epithelial Thickness in the spermatogenic epithelium, as well as the presence of a greater number of germ cells and mature sperm. In this study, Malva sylvestris treatment showed antioxidative effects since it upregulated the expression of SIRT1 and FOXO1 genes and downregulated the expression of NF-κB, NRF2, and TGF-β genes. CONCLUSION: Based on the findings, Malva sylvestris as cytoprotective agent modulate key antioxidant pathways, including upregulation of SIRT1 and FOXO1 (linked to cellular repair and OS resistance) and downregulation of pro-inflammatory mediators; then, Malva sylvestris as a promising natural antioxidant for managing varicocele-related infertility, offering a potential adjunct or alternative to conventional therapies.