Mechanistic insights into the antidepressant potential of plant-derived flavonoids: A preclinical review

Flavonoid-based phytomedicines are emerging as promising therapies for combating various disorders, including depression. Depression is a common and serious medical illness that negatively affects the quality of life. It has become a leading cause of disability worldwide. Flavonoids are ubiquitous biologically active phytochemicals in medicinal plants, herbs, fruits, vegetables, teas, and wines. There is a negative association between total flavonoid intake and depression symptoms in humans. This review aims to discuss the recent in vivo and in vitro studies on the effects of dietary flavonoids in depression models and assays to identify the molecular pathways that underlie their actions. Here, we briefly introduce the pathophysiology of depression, the diagnosis of depression, and the models for studying depression. The discovered potential antidepressant flavonoids include flavonols (quercetin, quercitrin, kaemferol, and heptamethoxyflavone), flavones (luteolin, baicalin, apigenin, and cymaroside), isoflavones (ononin), flavanones (pinocembrin), and anthocyanins (callistephin). These plant-derived flavonoids have been shown to reduce neuronal damage in the hippocampus, decrease neurotransmitter depletion, attenuate hypothalamic-pituitary-adrenal axis hyperactivation, inhibit inflammation in the central nervous system, and regulate gut microbiota. The key signaling pathways regulated by flavonoids include brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB), and nuclear factor kappa-B (NF-κB). Clearly, there is a need to conduct human dietary intervention studies to validate the beneficial physiological functions of flavonoids on the prevention and management of depression.