Investigation of the potential synergistic effects of probiotic and thymoquinone in the treatment of a corticosterone-induced mouse depression model

Türkmenoğlu B. Investigation of the Potential Synergistic Effects of Probiotic and Thymoquinone in the Treatment of A Corticosterone-Induced Mouse Depression Model Van Yuzuncu Yil Unıversıty Department of Medical Pharmacology (Medical Program), Instıtute of Health Sciences, Pharmacology (Medicine Program), Master's Thesis, Van, 2025. Depression is a common mental disorder that develops as a result of the interaction of neurobiological, behavioral, and immunological mechanisms. Recent studies indicate that gut microbiota, inflammation, and neuroplasticity play significant roles in the pathophysiology of depression. In this study, the behavioral and biochemical effects of probiotic (VSL#3) and thymoquinone (TQ), administered alone or in combination with fluoxetine, a selective serotonin reuptake inhibitor with antidepressant properties, were investigated in a corticosterone-induced depression model in mice.A total of 64 Swiss albino male mice were divided into eight groups: control, depression, depression + fluoxetine, depression + probiotic, depression + thymoquinone, depression + probiotic + fluoxetine, depression + thymoquinone + fluoxetine, and depression + thymoquinone + fluoxetine + probiotic. The depression model was established by subcutaneous administration of corticosterone at a dose of 40 mg/kg for 21 days. Treatment protocols were determined in accordance with the literature. Behavioral evaluations were performed using the Forced Swimming Test (FST), Tail Suspension Test (TST), and Sucrose Preference Test (SPT). Biochemical analyses of TNF-α, IL-1β, IL-6, Total Antioxidant Status (TAS), Total Oxidant Status (TOS), and Caspase-3 levels were performed using the ELISA method. According to the results, immobility times significantly increased in the corticosterone-induced depression group (p<0.05). A significant reduction in immobility time was observed in all treatment groups receiving probiotic, thymoquinone, and fluoxetine (p<0.05). In the sucrose preference test, marked anhedonia was observed in the depression group, while improvement was detected in the treatment groups (p<0.05). ELISA analyses revealed significant differences in inflammatory and oxidative stress markers among the groups (p<0.05). These findings suggest that probiotic and thymoquinone, especially when administered in combination with fluoxetine, may exhibit protective and therapeutic effects on depression-related behaviors. This study supports the potential contribution of psychobiotics and herbal bioactive compounds to antidepressant therapies and provides valuable data for future pharmacological approaches.