Antidepressant-like effects of aqueous extracts of miswak (Salvadora persica) and date palm (Phoenix dactylifera) on depression-like behaviors using CUMS model in male rats.

This study aimed to evaluate the antidepressant-like effects of aqueous extracts of miswak (Salvadora persica) and date palm (Phoenix dactylifera) and their combination on depression-like behaviors using a chronic unpredictable mild stress (CUMS) rat model of depression and to investigate the underlying possible mechanisms. Results showed that CUMS induced depression-like behaviors and anxiety in male rats, as determined by behavioral tests (FST, EPM, and OFT). CUMS significantly increased the levels of plasma malondialdehyde (MDA), cortisol, and pro-inflammatory cytokines (TNF-α and IL-6), in addition to enhancing acetylcholinesterase (ACHE) activity while plasma total antioxidant capacity and serotonin level were reduced. In the prefrontal cortex, CUMS decreased the expression of CREB and BDNF mRNA. However, aqueous extracts of miswak and date palm and their combination effectively ameliorated depressive-like behaviors, body weight loss, and oxidative stress induced by CUMS and restored serotonin and cortisol secretion to normal levels. Furthermore, the studied extracts improved the levels of plasma pro-inflammatory cytokines and CREB and BDNF mRNA expression in the prefrontal cortex. In conclusion, aqueous extracts of miswak and date palm have significant antidepressant-like effects on depression-like behaviors in CUMS model in rats. Moreover, their combination has higher antidepressant-like effects than either extract alone, suggesting that it may be an effective treatment for stress-induced depression-like behaviors acting through modulating pro-inflammatory cytokines and CREB/BDNF signaling pathway in the prefrontal cortex. PRACTICAL APPLICATIONS: Chronic stress is a major contributor to the development of depression. In recent years, there has been a significant increase in the use of herbal remedies for the treatment of a variety of diseases, particularly mood disorders. Because of the side effects encountered by antidepressant drugs such as anxiety, sexual dysfunction, loss of appetite, and inadequate response or developing tolerance to these medications, there is a need for more efficient and convenient antidepressant treatments. According to this study, aqueous extracts of miswak and date palm are effective treatments for stress-induced depression-like behaviors.