Suppression of Lipopolysaccharide-Induced Neuroinflammation by Morin via MAPK, PI3K/Akt, and PKA/HO-1 Signaling Pathway Modulation

Morin is a flavonoid isolated from certain fruits and Chinese herbs and is known to possess various Medicinal properties. In this study, we investigated the anti-inflammatory effects of morin on lipopolysaccharide (LPS)-inducedmicroglial activation, both in vitro and in vivo. We found that morin inhibited inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines in LPS-stimulated BV2 microglial cells. Furthermore, morin suppressed the microglial activation and cytokine expression in the brains of LPS-stimulated mice. Subsequent mechanistic studies revealed that morin inhibited the action of LPS-activated mitogen-activated protein kinases (MAPKs), protein kinase B (Akt) phosphorylation, nuclear factor-kappa B (NP-kappa B), and activating protein-1 (AP-1). Further, the phosphorylation and DNA binding activity of CAMP responsive element binding protein (CRPB) was enhanced by morin. Moreover, morin suppressed the LPS-induced exptession of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, while it increased heme oxygetiase-1 (HO-1) expression and nuclear factor erythroid related factor 2 (Nrf2) activation. Therefore, our data suggest that morin exerts anti-inflammatory effects in LPS-stimulated microglia by downregulating MAPK and phosphatidylinositol 3-kinase(PI3K)/Akt signaling pathways while upregulating protein kinase A (PKA)/CREB and Nrf2/HO-1 signaling pathways.