Research Progress on Flavonoids Regulating Microglial Function to Ameliorate Cognitive Impairment

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Alzheimer’s disease represents the most prevalent form of dementia. Neuroinflammation triggered by homeostatic imbalance and excessive activation of microglia serves as the core pathological mechanism underlying cognitive decline. As naturally occurring polyphenols with high biosafety, flavonoids are capable of crossing the blood–brain barrier and exert multi-target regulatory effects oncentral nervousinflammation, rendering them promising naturalbioactiveagentsfor intervening cognitive impairment. Focusing on four subclasses including flavones, flavonols, flavanones and isoflavones, this paper systematically summarizes the molecular mechanisms by which various flavonoid monomers confer neuroprotective effects and alleviate cognitive damage. Such mechanisms comprise modulating M1/M2 polarization of microglia, blocking inflammatory signaling cascades such as NF-κB, MAPK and NLRP3 inflammasome, inhibiting amyloid-β (Aβ) deposition, ameliorating oxidative stress and correcting gut microbiota dysbiosis. Meanwhile, this review highlights that insufficient bioavailability restricts the clinical translation of flavonoids, while delivery technologies including nanoformulations and targeted sustained-release hydrogels can effectively overcome this limitation, providing theoretical evidence for the research and developmentofnaturalmedicinesagainstAlzheimer’sdisease.

• 1N4455144535P3-2854.pdf