Naringenin promotes microglial M2 polarization and Aβ degradation enzyme expression

Abstract

Two kinds of microglia are known, classical M1 and alternative M2 phenotypes. Amyloid β (Aβ), a critical cause of Alzheimer's disease (AD), promotes M1 microglial polarization, leading to neuroinflammation and neuronal death. M2 microglia play important roles in anti-inflammatory effects, Aβ clearance, and memory recovery in AD. Therefore, increasing of M2 microglia is expected to recover from AD. We previously found that naringenin, a blood-brain barrier penetrating compound, decreased Aβ deposits and recovers memory function in transgenic AD model mice. Naringenin reportedly showed anti-inflammatory properties. Here, we aim to investigate potential effects of naringenin on microglial polarization and to reveal the underlying mechanisms of Aβ reduction. Primary cultured cortical microglia were treated with Aβ_1-42 , following administration of naringenin. Naringenin remarkably promoted M2 microglia polarization and inhibited Aβ_1-42 -induced M1 microglia activation. Because microglia reportedly played a critical role in cerebral Aβ clearance through Aβ degradation enzymes after phagocytosis, we investigated the expression of Aβ degradation enzymes, such as neprilysin and insulin degradation enzyme. After naringenin treatment, these Aβ degradation enzymes were downregulated in M1 microglia and upregulated in M2 microglia. Taken together, our results showed that naringenin increased Aβ degradation enzymes in M2 microglia, probably leading to Aβ plaque reduction.

Keywords: Aβ degradation enzyme; M2 polarization; microglia; naringenin.