Interaction of Concurrent Exercise Training and Milk thistle Extract on Hippocampi, NF-κB, and Serotonin of PTSD in Male Rats

Introduction: Post-traumatic stress disorder (PTSD) is characterized by chronic neuroinflammation, impaired serotonergic signaling, and structural damage in both central and peripheral tissues, including the hippocampus and liver. Nuclear factor kappa B (NF-κB) plays a central role in stress-induced inflammatory responses. Exercise and phytotherapeutic agents such as milk thistle (Silybum marianum) have been suggested as potential non-pharmacological strategies for attenuating PTSD-related pathophysiology. Methods: Fifty-five male Wistar rats were randomly assigned to five groups: healthy control, PTSD, PTSD with concurrent exercise training, PTSD with milk thistle extract, and PTSD with concurrent exercise training plus milk thistle extract. PTSD was induced using a multi-stage stress protocol. The concurrent exercise training program was conducted for ۴ weeks, consisting of resistance training on even days and aerobic training on odd days. Resistance training was performed with progressively increasing loads from ۵۰% to ۸۰% of body weight, and aerobic training from ۵۰% to ۸۰% of VO₂max. Milk thistle extract was administered daily at a dose of ۳۰۰ mg/kg. After the intervention, hippocampal and liver tissues were collected. NF-κB mRNA expression was measured using real-time PCR, and serotonin levels were measured by ELISA. Histopathological alterations were assessed by hematoxylin and eosin staining. Data were analyzed using ANOVA and Tukey statistical tests. Results: PTSD induction significantly increased NF-κB mRNA expression and decreased serotonin levels in both hippocampal and liver tissues compared with healthy controls. Concurrent exercise training and milk thistle extract each significantly attenuated NF-κB overexpression and partially restored serotonin levels (p < ۰.۰۵). Histopathological analysis revealed severe neuronal degeneration in the hippocampus and marked structural damage in liver tissue in PTSD rats, whereas both interventions, particularly their combination, markedly improved tissue morphology. Conclusion: Concurrent exercise training and milk thistle extract exert synergistic neuroprotective and hepatoprotective effects in a rat model of PTSD. These benefits appear to be mediated through suppression of NF-κB–dependent inflammatory pathways and restoration of serotonergic homeostasis.

کلیدواژه ها:

PTSD ، Exercise Training ، Milk Thistle Extract ، Serotonin ، NF-κB