Flavonoids in the regulation of microglial-mediated neuroinflammation; focus on fisetin, rutin, and quercetin

Neuroinflammation is a critical mechanism in central nervous system (CNS) inflammatory disorders, encompassing conditions such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS), traumatic brain injury (TBI), encephalitis, spinal cord injury (SCI), and cerebral stroke. Neuroinflammation is characterized by increased blood vessel permeability, leukocyte infiltration, glial cell activation, and elevated production of inflammatory mediators, such as chemokines and cytokines. Microglia act as the resident macrophages of the central nervous system, serving as the principal defense mechanism in brain tissue. After CNS injury, microglia modify their morphology and downregulate genes that promote homeostatic functions. Despite comprehensive transcriptome analyses revealing specific gene modifications in "pathological" microglia, microglia's precise protective or harmful functions in neurological disorders remain insufficiently comprehended. Accumulating data suggests that the polarization of microglia into the M1 proinflammatory phenotype or the M2 antiinflammatory phenotype may serve as a sensible therapeutic strategy for neuroinflammation. Flavonoids, including rutin, fisetin, and quercetin, function as crucial chemical reservoirs with unique structures and diverse actions and are extensively used to modulate microglial polarization in treating neuroinflammation. This paper highlights the detrimental effects of neuroinflammation seen in neurological disorders such as stroke. Furthermore, we investigate their therapeutic benefits in alleviating neuroinflammation via the modulation of macrophage polarization.