The mechanism of natural dietary polyphenols on inhibiting inflammation and modulating gut-brain axis: an effective way to prevent depression

Abstract

Depression is a leading global public health concern, and current pharmacotherapies are often limited by adverse effects during long-term use. Natural dietary polyphenols have attracted attention as safer alternatives, supported by growing evidence of their antidepressant potential. This review synthesizes current findings on the mechanisms through which polyphenols alleviate depressive symptoms, with a particular focus on the microbiota-gut-brain (MGB) axis. A total of 3 key pathways are highlighted: 1) reshaping gut microbial composition and enhancing the production of beneficial metabolites such as short-chain fatty acids (SCFAs); 2) suppressing neuroinflammation by inhibiting pro-inflammatory cytokines and normalizing hypothalamic-pituitary-adrenal (HPA) axis activity; and 3) promoting neuroplasticity via up-regulation of neurotransmitters and brain-derived neurotrophic factor (BDNF). Collectively, these actions converge to improve mood regulation and cognitive function, and this review underscores the therapeutic potential of polyphenols as natural bioactive agents for depression. Further well-designed studies are warranted to clarify dose-response relationships, microbiota-dependent variability, and translational applicability in humans.