title: Suppression of Lipopolysaccharide-Induced Neuroinflammation by Morin via MAPK, PI3K/Akt, and PKA/HO-1 Signaling Pathway Modulation.
abstract: 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.
authors.affiliation: Division of Functional Food Research, Korea Food Research Institute , Gyeonggi-do 463-746, Republic of Korea.
authors.forename: Ji-Sun
authors.initials: JS
authors.lastname: Jung
authors.forename: Min-Ji
authors.initials: MJ
authors.lastname: Choi
authors.forename: Yu Young
authors.initials: YY
authors.lastname: Lee
authors.forename: Byung-In
authors.initials: BI
authors.lastname: Moon
authors.forename: Jin-Sun
authors.initials: JS
authors.lastname: Park
authors.forename: Hee-Sun
authors.identifier: http://orcid.org/0000-0003-1889-8739
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D008565:Membrane Proteins / Q000378:metabolism; D008813:Mice, Inbred ICR; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D018805:Sepsis / Q000139:chemically induced / Q000188:drug therapy; D015398:Signal Transduction / Q000187:drug effects; D047309:Flavones
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D017868:Cyclic AMP-Dependent Protein Kinases; D016207:Cytokines; D005419:Flavonoids; D051547:Heme Oxygenase-1; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D020928:Mitogen-Activated Protein Kinases; D018696:Neuroprotective Agents; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species; C008548:morin; D047309:Flavones; C496542:Hmox1 protein, mouse
keywords: anti-inflammation; microglia; molecular mechanisms; morin; neuroinflammation