Anxiolytic, Antidepressant and Healthy Sleep-Promoting Potential of Rosmarinic Acid: Mechanisms and Molecular Targets

Vijayan Priya,1 Dhiyanesh Srinivasan,1 Swagatika Priyadarsini,2 Fatemeh Dabaghzadeh,3 Sandeep Singh Rana,4 Jeevitha Gada Chengaiyan,4 Ravi Sudesh,5 Faraz Ahmad1 1Department of Biotechnology, School of Bio Sciences and Technology (SBST), Vellore Institute of Technology (VIT), Vellore, India, 632014; 2ICAR-National Research Centre on Camel (NRCC), Bikaner, India, 334001; 3Department of Clinical Pharmacy, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran; 4Department of Biosciences, School of Bio Sciences and Technology (SBST), Vellore Institute of Technology (VIT), Vellore, 632014 India; 5Department of Biomedical Science, School of Bio Sciences and Technology (SBST) Vellore Institute of Technology (VIT), Vellore, 632014, IndiaCorrespondence: Faraz Ahmad, Department of Biotechnology, School of Bio Sciences and Technology (SBST), Vellore Institute of Technology (VIT), Vellore, 632014, India, Email [email protected] Ravi Sudesh, Department of Biomedical Science, School of Bio Sciences and Technology (SBST), Vellore Institute of Technology (VIT), Vellore, 632014, India, Email [email protected]: The etiology of psychiatric disorders is complex and results from intricate interactions among multiple neurobiological, psychological, environmental, and genetic factors. Furthermore, the roles of gut microbiome dyshomeostasis in their pathogeneses are just beginning to be uncovered, adding to another level of complexity. In recent years, significant efforts have been directed toward discovering multimodal yet safe therapeutics to counteract psychological deficits. Rosmarinic acid (RA), a polyphenol found in several medicinal herbs, has received considerable attention as a potential multifaceted therapeutic agent, particularly for neuropsychiatric conditions. In order to critically evaluate this aspect, data was compiled and consolidated after extensive searches on scholarly databases like PubMed, Google Scholar, and Web of Science. Peer-reviewed publications which focused on RA as a therapeutic agent for psychiatric disorders were included regardless of the year of publication and country of origin. Based on pre-clinical and clinical evidence, this review delves into the various mechanistic aspects of the antidepressant, anxiolytic, and sleep-promoting functions of RA. The beneficial effects of RA on the gut-microbiome-brain (GMB) axis and their implications for the regulation of neuroprotective pathways are also discussed, with a particular focus on exploiting them to ameliorate neuropsychiatric conditions. Our assessment indicated that RA is a multimodal neuroprotectant against psychiatric conditions and beneficially influences a plethora of targets related to redox, inflammatory, synaptic, cell death, neurotrophic, and cell signaling pathways. As a dietary agent, RA may also be relevant in favorably altering the GMB axis, indicating its prospects as a potential multimodal adjuvant therapeutic agent in regulating the pathogenic mechanisms underlying neuropsychiatric conditions. However, more extensive clinical studies are required to ascertain the neuromodulatory actions of RA in neuronal pathophysiologies, including psychiatric ailments.Keywords: psychiatric disorders, circadian rhythm, gut-microbiome-brain axis, phytotherapy, traditional medicine