Protective effects of Withania somnifera (Ashwagandha) against chronic unpredictable mild stress-induced testicular damage in adolescent rats.

This study aimed to comparatively investigate the protective effects of Ashwagandha and Sertraline treatments on chronic stress-induced testicular damage and reproductive dysfunction in adolescent rats, through hormonal, biochemical, and apoptotic pathways. Twenty-eight adolescent male Wistar albino rats were divided into four groups: Control, Chronic Unpredictable Mild Stress (CUMS)-induced Depression, Depression+Sertraline, and Depression+Ashwagandha. Testicular testosterone and cyclic guanosine monophosphate (cGMP) levels, as well as oxidative stress markers and inflammatory cytokines in the testicular tissue, were measured. Johnsen scoring and H&E staining were performed to evaluate histopathological changes. Immunohistochemically, Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), marker of proliferation Ki-67 (Ki67), and Sirtuin 6 (SIRT6) antibodies were evaluated. Chronic stress exposure led to a significant decrease in testicular testosterone and cGMP levels, while causing an increase in oxidative stress and inflammation markers. Histopathological examinations revealed desquamation of the seminiferous tubule epithelium, tubular degeneration, and a severe reduction in the Johnsen score in the depression group. At the molecular level, it was observed that stress increased Bax expression and suppressed Bcl-2 expression. Ki67 and SIRT6 levels were decreased in the Depression group. Both treatment modalities increased Bcl-2, Ki67, and SIRT6 immunoreactivities. It was observed that the Bax/Bcl-2 ratio in the Ashwagandha group approached the levels of the control group. Both treatment methods alleviated oxidative, inflammatory, and apoptotic changes triggered by chronic stress in the testes of adolescent rats. Mitigating testosterone depletion and strengthening anti-apoptotic defense mechanisms, Ashwagandha provides more comprehensive protection compared to Sertraline. These findings suggest that Ashwagandha may serve as a potential phytotherapeutic supportive agent in mitigating stress-induced damage within the testicular tissue.