Flavonoids as Modulators of Neuroinflammation in Affective Disorders: A Narrative Review

Affective disorders, including anxiety, depression, and bipolar disorder (BD), represent a global mental health burden with complex, multifactorial etiopathogenesis. Increasing evidence implicates neuroinflammation, oxidative stress, and dysregulation of neurotrophic and neurotransmitter systems as central mechanisms driving these conditions. Flavonoids, a structurally diverse class of plant-derived polyphenolic compounds abundantly found in fruits, vegetables, tea, and other dietary sources, have emerged as promising modulators of these pathophysiological pathways. This narrative review synthesizes current preclinical and clinical evidence on the role of flavonoids and related natural compounds in modulating neuroinflammation and affective disorders. We describe the major flavonoid subclasses-flavones, flavonols, isoflavones, anthocyanins, flavanones, and flavan-3-ols-and analyze their mechanisms of action, including inhibition of the NF-κB/NLRP3 axis, reduction in pro-inflammatory cytokines, attenuation of oxidative stress via Nrf2 pathway activation, modulation of monoaminergic and GABAergic neurotransmission, promotion of Brain-Derived Neurotrophic Factor (BDNF)-mediated neuroplasticity, and regulation of the microbiota-gut-brain axis. Preclinical studies consistently demonstrate anxiolytic and antidepressant effects for compounds such as quercetin, luteolin, apigenin, and chrysin; however, clinical evidence remains limited and methodologically heterogeneous. Future research should prioritize bioavailability-enhanced formulations, standardized clinical trials, and biomarker-guided stratification to fully establish the therapeutic potential of flavonoids in affective disorders.