Phytochemicals Modulate Biosynthesis and Function of Serotonin, Dopamine, and Norepinephrine for Treatment of Monoamine Neurotransmission-Related Psychiatric Diseases
Makoto Naoi, Yuqiu Wu, Wakako Maruyama, Masayo Shamoto‐Nagai
Abstract
Serotonin (5-HT), dopamine (DA), and norepinephrine (NE) are key monoamine neurotransmitters regulating behaviors, mood, and cognition. 5-HT affects early brain development, and its dysfunction induces brain vulnerability to stress, raising the risk of depression, anxiety, and autism in adulthood. These neurotransmitters are synthesized from tryptophan and tyrosine via hydroxylation and decarboxylation, and are metabolized by monoamine oxidase (MAO). This review aims to summarize the current findings on the role of dietary phytochemicals in modulating monoamine neurotransmitter biosynthesis, metabolism, and function, with an emphasis on their potential therapeutic applications in neuropsychiatric disorders. Phytochemicals exert antioxidant, neurotrophic, and neurohormonal activities, regulate gene expression, and induce epigenetic modifications. Phytoestrogens activate the estrogen receptors or estrogen-responsive elements of the promoter of target genes, enhance transcription of tryptophan hydroxylase and tyrosine hydroxylase, while inhibiting that of MAO. These compounds also influence the interaction between genetic and environmental factors, potentially reversing dysregulated neurotransmission and the brain architecture associated with neuropsychiatric conditions. Despite promising preclinical findings, clinical applications of phytochemicals remain challenging. Advances in nanotechnology and targeted delivery systems offer potential solutions to enhance clinical efficacy. This review discusses mechanisms, challenges, and strategies, underscoring the need for further research to advance phytochemical-based interventions for neuropsychiatric diseases.