title: Morin downregulates nitric oxide and prostaglandin E2 production in LPS-stimulated BV2 microglial cells by suppressing NF-κB activity and activating HO-1 induction.
abstract: Morin possesses anti-inflammatory activity against septic shock and allergic responses, and prevents acute liver damage. However, the biological mechanism of action of morin in neuroinflammation remains largely unknown. Therefore, the present study investigated whether morin has the ability to attenuate expression of proinflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Morin inhibited the expression of LPS-induced proinflammatory mediators such as NO and PGE2, without any cytotoxic effects. Furthermore, LPS-induced inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) were inhibited both at the mRNA and protein levels in response to morin. Morin also attenuated LPS-induced DNA-binding activity of nuclear transcription factor-κB (NF-κB) and its promoter activity. Pyrrolidine dithiocarbamate (PDTC), a specific NF-κB inhibitor, downregulated the expression of LPS-induced iNOS and COX-2, which suggests that morin-mediated NF-κB inhibition is the main signaling pathway responsible for the inhibition of iNOS and COX-2 expression. Additionally, morin increased induction of heme oxygenase-1 (HO-1) activity, leading to the suppression of NO and PGE2 production. Our results indicate that morin downregulates the expression of proinflammatory genes, such as iNOS and COX-2, involved in the synthesis of NO and PGE2 in LPS-stimulated BV2 microglial cells by suppressing NF-κB activity and activation of HO-1. Taken together, the findings of the present study suggest that morin may have potential as a therapeutic for the prevention of neuroinflammation.
authors.affiliation: Department of Marine Life Sciences, Jeju National University, Jeju 63243, Republic of Korea.
authors.forename: Matharage Gayani
authors.initials: MG
authors.lastname: Dilshara
authors.affiliation: Department of Marine Life Sciences, Jeju National University, Jeju 63243, Republic of Korea.
authors.forename: Rajapaksha Gedara Prasad Tharanga
authors.initials: RG
authors.lastname: Jayasooriya
authors.affiliation: Department of Marine Life Sciences, Jeju National University, Jeju 63243, Republic of Korea.
authors.forename: Seungheon
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, College of Oriental Medicine, Dong-Eui University, Busan47340, Republic of Korea.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Department of Marine Life Sciences, Jeju National University, Jeju 63243, Republic of Korea. Electronic address: immunkim@jejunu.ac.kr.
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D015536:Down-Regulation; D005419:Flavonoids / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D047309:Flavones
chemical_list: D000893:Anti-Inflammatory Agents; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D005419:Flavonoids; D051547:Heme Oxygenase-1; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D016328:NF-kappa B; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C008548:morin; D047309:Flavones; C496317:Nos2 protein, mouse; C496542:Hmox1 protein, mouse; C077623:Ptgs2 protein, mouse
keywords: Heme oxygenase-1; Morin; Nitric oxide; Nuclear factor-κB; Prostaglandin E(2)