Phytochemicals targeting oxidative stress, interconnected neuroinflammatory and neuroapoptotic pathways following radiation.

Background Withania somnifera (WS), also known as Ashwagandha, is commonly used in Ayurveda and other traditional medicine systems. WS has seen growing, worldwide use by the public due to its reputation as an adaptogen. This popularity has elicited increased scientific study of its biological effects, including a potential application for neuropsychiatric and neurodegenerative disorders. Objective This review aims to provide a comprehensive summary of preclinical and clinical studies examining the neuropsychiatric effects of WS, specifically its application in stress, anxiety, depression, and insomnia. Methods Reports of human trials and animal studies of WS were collected primarily from the PubMed, Scopus, and Google Scholar databases. Results WS root and leaf extracts exhibited noteworthy anti-stress and anti-anxiety activity in animal and human studies. WS also improved symptoms of depression and insomnia, though fewer studies investigated these applications. WS may alleviate these conditions predominantly through modulation of the hypothalamic-pituitary-adrenal and sympathetic-adrenal medullary axes, as well as through GABAergic and serotonergic pathways. While some studies link specific withanolide components to its neuropsychiatric benefits, there is evidence for the presence of additional, yet unidentified, active compounds in WS. Conclusion While benefits were seen in the reviewed studies, significant variability in the WS extracts examined prevents a consensus on the optimum WS preparation or dosage to treat neuropsychiatric conditions. WS appears generally safe for human use; however, it will be important to investigate potential herb-drug interactions involving WS if used alongside pharmaceutical interventions. Further elucidation of active compounds of WS is also needed.