Ferulic acid as a therapeutic agent in depression: Evidence from preclinical studies

Depression is a common but severe mood disorder with a very high prevalence across the general population. Depression is of global concern and poses a threat to human physical and mental health. Ferulic acid (FA) is a natural active ingredient that has antioxidative, anti-inflammatory, and free radical scavenging properties. Furthermore, studies have shown that FA can exert antidepressant effects through a variety of mechanisms. The aim of the review was to comprehensively elucidate the mechanisms in FA that alleviate depression using animal models. The in vivo (animal) studies on the mechanism of FA treatment of depression were searched in PubMed, Chinese National Knowledge Infrastructure, Baidu academic, and Wan fang databases. Thereafter, the literature conclusions were summarized accordingly. Ferulic acid was found to significantly improve the depressive-like behaviors of animal models, suggesting that FA is a potential natural product in the treatment of depression. The mechanisms are achieved by enhancing monoamine oxidase A (MOA) activity, inhibiting microglia activation and inflammatory factor release, anti-oxidative stress, promoting hippocampal nerve regeneration, increasing brain-derived neurotrophic factor secretion, regulating gut microbiome, and activating protein kinase B/collapsin response mediator protein 2 (AKT/CRMP2) signaling pathway. Ferulic acid produces significant antidepressant effects in animal depression models through various mechanisms, suggesting its potential value as a treatment of depression. However, clinical research trials involving FA are required further to provide a solid foundation for its clinical application.