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

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• 作者：Ji-Sun Jung ; Min-Ji Choi ; Yu Young Lee ; Byung-In Moon ; Jin-Sun Park ; Hee-Sun Kim
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2017
• 出版时间：January 18, 2017
• 年：2017
• 卷：65
• 期：2
• 页码：373-382
• 全文大小：767K
• ISSN：1520-5118

文摘

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)-induced microglial 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-κB (NF-κB), and activating protein-1 (AP-1). Further, the phosphorylation and DNA binding activity of cAMP responsive element binding protein (CREB) was enhanced by morin. Moreover, morin suppressed the LPS-induced expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, while it increased heme oxygenase-1 (HO-1) expression and nuclear factor erythroid 2-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.