The natural (poly)phenols as modulators of microglia polarization via TLR4/NF-κB pathway exert anti-inflammatory activity in ischemic stroke

Increasing evidences suggest that inflammation plays a key role in the pathogenesis of stroke, a devastating disease second only to cardiac ischemia as a cause of death worldwide. Microglia are the first non-neuronal cells on the scene during the innate immune response to acute ischemic stroke. Microglia respond to acute brain injury by activating and developing classic M1-like (pro-inflammatory) or alternative M2-like (anti-inflammatory) phenotypes. M1 microglia produce pro-inflammatory cytokines to exacerbate neural death, astrocyte apoptosis, and blood brain barrier (BBB) disruption, while M2 microglia play the opposite role. NF-κB, a central regulator of the inflammatory response, was responsible for microglia M1 and M2 polarization. NF-κB p65 and p50 form a heterodimer to initiate a pro-inflammatory cytokine response, which enhances M1 activation and impair M2 response of microglia. TLR4, expressed on the surface of microglia, plays an important role in activating NF-κB, ultimately causing the M1 response of microglia. Therefore, modulation of microglial phenotypes via TLR4/NF-κB signaling pathway may be a promising therapeutic approach for ischemic stroke. Dietary (poly)phenols are present in various foods, which have shown promising protective effects on ischemic stroke. In vivo studies strongly suggest that many (poly)phenols have a pronounced impact on ischemic stroke, as demonstrated by lower neuroinflammation. Thus, this review focuses on the anti-inflammatory properties of dietary (poly)phenols and discusses their effects on the polarization of microglia through modulating TLR4/NF-κB signaling pathway in the ischemic stroke.