Ferulic acid: An extraordinarily neuroprotective phenolic acid with anti-depressive properties

Depression, one of the most common mental illnesses and mood disorder syndromes, can seriously harm physical and mental health. As the pathophysiology of depression remains unclear, there is a need to find novel therapeutic agents. Ferulic acid (FA), a phenolic compound found in various Chinese herbal medicines, has anti-inflammatory and free radical scavenging properties as well as a wide range of therapeutic effects against depression.In this review, we appraised preclinical research to fully discuss the anti-depression capacity of FA and discussed FAs' holistic characteristics that can contribute to better management of depression.We reviewed the results of in vitro and in vivo experiments using FA to treat depression and explored the possible antidepressant pharmacological mechanisms of FA for the clinical treatment of depression.Electronic databases, including PubMed, Google Scholar, and China National Knowledge Infrastructure, were searched from the beginning of the database creation to December 2021.Studies on the antidepressant effects of FA show that it may exert such effects through various mechanisms. These include the following: the regulation of monoamine and non-monoamine neurotransmitter levels, inhibition of hypothalamic-pituitary-adrenal axis hyperfunction and neuroinflammation, promotion of hippocampal neurogenesis and upregulation brain-derived neurotrophic factor level, neuroprotection (inhibition of neuroinflammation, oxidative stress, mitochondrial dysfunction, and apoptosis), and downregulation of oxidative stress.Preclinical studies on the antidepressant effects of FA were reviewed in this study, and research on the antidepressant mechanisms of FA was summarized, confirming that FA can exert antidepressant effects through various pharmacological mechanisms. However, more multicenter clinical case-control studies are needed to confirm the clinical efficacy of FA.