Macelignan inhibits the inflammatory response of microglia and regulates neuronal survival

Abstract

Neuroinflammation is an important pathological process of neurodegenerative diseases, and microglial contributes to chronic inflammation and neuronal loss in progressive neurodegenerative. Therefore, regulating the inflammatory response of microglia could lead to the discovery of promising treatments for neurodegenerative diseases. In this study, we investigated the effects of the nutmeg plant seed extract, macelignan, on the inflammatory response of microglia and neuronal cell survival. We detected NO and iNOS using the Griess test and Western blotting. We measured phosphoinositide 3 kinase (PI3K)/Akt expression by Western blotting. The release of NO and inflammatory cytokines and the expression of iNOS decreased in a concentration-dependent manner, with an increase in macelignan concentration. PI3K/Akt phosphorylation levels decreased in a dose-dependent manner in lipopolysaccharide (LPS)-activated microglial cells after exposure to macelignan. We also demonstrated that macelignan improved HT22 cell viability, following exposure to a microglial-conditioned medium. Furthermore, macelignan inhibited microglial cell near neurons treated with a hypoxic conditioned medium. Finally, macelignan treatment reduced the expression of p27 and cyclin D1 in neurons cultured in an LPS-activated microglia-conditioned medium. Therefore, these results imply that macelignan can inhibit the inflammatory response of microglia and regulate neuronal survival through the PI3K/Akt pathway.