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

Area of Science:

• Neuroscience and Pharmacology
• Nutritional Psychiatry
• Natural Product Chemistry

Background:

• Affective disorders (anxiety, depression, bipolar disorder) pose a significant global mental health challenge.
• Neuroinflammation, oxidative stress, and neurotransmitter dysregulation are key mechanisms in affective disorders.
• Flavonoids, plant-derived polyphenols, are increasingly recognized for their potential to modulate these pathways.

Purpose of the Study:

• To review preclinical and clinical evidence on flavonoids' role in modulating neuroinflammation and affective disorders.
• To analyze the mechanisms of action of major flavonoid subclasses.
• To identify gaps and future directions for research.

Main Methods:

• Narrative review of preclinical and clinical studies.
• Analysis of flavonoid subclasses (flavones, flavonols, isoflavones, anthocyanins, flavanones, flavan-3-ols).
• Examination of mechanisms including NF-κB/NLRP3 inhibition, Nrf2 activation, neurotransmitter modulation, BDNF signaling, and gut-brain axis regulation.

Main Results:

• Preclinical studies show anxiolytic and antidepressant effects for flavonoids like quercetin, luteolin, apigenin, and chrysin.
• Flavonoids modulate key pathways: reducing inflammation, oxidative stress, and influencing neurotransmission and neuroplasticity.
• Clinical evidence is currently limited and heterogeneous, with a need for more robust studies.

Conclusions:

• Flavonoids demonstrate significant potential as therapeutic agents for affective disorders through multi-target mechanisms.
• Enhanced bioavailability and standardized clinical trials are crucial for validating their efficacy.
• Future research should focus on biomarker-guided approaches to optimize flavonoid-based interventions.