Beneficial effects of natural flavonoids on neuroinflammation

Abstract

Neuroinflammation is the fundamental immune response against multiple factors in the central nervous system and is characterized by the production of inflammatory mediators, activated microglia and astrocytes, and the recruitment of innate and adaptive immune cells to inflammatory sites, that contributes to the pathological process of related brain diseases, such as Alzheimer's disease, Parkinson's disease, depression, and stroke. Flavonoids, as a species of important natural compounds, have been widely revealed to alleviate neuroinflammation by inhibiting the production of pro-inflammatory mediators, elevating the secretion of anti-inflammatory factors, and modulating the polarization of microglia and astrocyte, mainly via suppressing the activation of NLRP3 inflammasome, as well as NF-κB, MAPK, and JAK/STAT pathways, promoting Nrf2, AMPK, BDNF/CREB, Wnt/β-Catenin, PI3k/Akt signals and SIRT1-mediated HMGB1 deacetylation. This review will provide the latest and comprehensive knowledge on the therapeutic benefits and mechanisms of natural flavonoids in neuroinflammation, and the natural flavonoids might be developed into food supplements or lead compounds for neuroinflammation-associated brain disorders.

Keywords: astrocytes; brain disorders; microglia; natural flavonoids; neuroinflammation.

Figure 1

Structures of flavones and flavonols with anti-neuroinflammatory effects.

Figure 2

Structures of flavanones and flavanonols with anti-neuroinflammatory effects.

Figure 3

Structures of isoflavones with anti-neuroinflammatory effects.

Figure 4

Structures of chalcones and dihydrochalcone with anti-neuroinflammatory effects.

Figure 5

Structures of other flavonoids with anti-neuroinflammatory effects.

Figure 6

Overview of the pathological course of neuroinflammation and the mechanisms of natural flavonoids against neuroinflammation. (A) Under neuroinflammation state, microglia and astrocytes are activated and secrete a lot of inflammatory cytokines, chemokines, along with small-molecule messengers which disturb the normal functioning of neurons and cause damage in brain tissue. (B) Natural flavonoids play anti-neuroinflammatory effects via inhibiting the activation of NLRP3 inflammasome and MAPKs, JAK/STAT, NF-κB pathways, promoting Nrf2, AMPK, BDNF/CREB, Wnt/β-Catenin, PI3k/Akt pathways and SIRT1-mediated HMGB1 deacetylation.