PMID- 27131287 OWN - NLM STAT- MEDLINE DCOM- 20170208 LR - 20220409 IS - 1872-7077 (Electronic) IS - 1382-6689 (Linking) VI - 44 DP - 2016 Jun TI - Morin downregulates nitric oxide and prostaglandin E2 production in LPS-stimulated BV2 microglial cells by suppressing NF-kappaB activity and activating HO-1 induction. PG - 62-8 LID - S1382-6689(16)30087-4 [pii] LID - 10.1016/j.etap.2016.04.010 [doi] AB - 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-kappaB (NF-kappaB) and its promoter activity. Pyrrolidine dithiocarbamate (PDTC), a specific NF-kappaB inhibitor, downregulated the expression of LPS-induced iNOS and COX-2, which suggests that morin-mediated NF-kappaB 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-kappaB 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. CI - Copyright (c) 2016 Elsevier B.V. All rights reserved. FAU - Dilshara, Matharage Gayani AU - Dilshara MG AD - Department of Marine Life Sciences, Jeju National University, Jeju 63243, Republic of Korea. FAU - Jayasooriya, Rajapaksha Gedara Prasad Tharanga AU - Jayasooriya RG AD - Department of Marine Life Sciences, Jeju National University, Jeju 63243, Republic of Korea. FAU - Lee, Seungheon AU - Lee S AD - Department of Marine Life Sciences, Jeju National University, Jeju 63243, Republic of Korea. FAU - Choi, Yung Hyun AU - Choi YH AD - Department of Biochemistry, College of Oriental Medicine, Dong-Eui University, Busan47340, Republic of Korea. FAU - Kim, Gi-Young AU - Kim GY AD - Department of Marine Life Sciences, Jeju National University, Jeju 63243, Republic of Korea. Electronic address: immunkim@jejunu.ac.kr. LA - eng PT - Journal Article DEP - 20160422 PL - Netherlands TA - Environ Toxicol Pharmacol JT - Environmental toxicology and pharmacology JID - 9612020 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Flavonoids) RN - 0 (Lipopolysaccharides) RN - 0 (Membrane Proteins) RN - 0 (NF-kappa B) RN - 31C4KY9ESH (Nitric Oxide) RN - 8NFQ3F76WR (morin) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.13.39 (Nos2 protein, mouse) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - EC 1.14.14.18 (Hmox1 protein, mouse) RN - EC 1.14.99.- (Ptgs2 protein, mouse) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - Animals MH - Anti-Inflammatory Agents/*pharmacology MH - Cell Line MH - Cyclooxygenase 2/genetics/metabolism MH - Dinoprostone/*metabolism MH - Down-Regulation MH - Flavonoids/*pharmacology MH - Heme Oxygenase-1/genetics/*metabolism MH - Lipopolysaccharides MH - Membrane Proteins/genetics/*metabolism MH - Mice MH - Microglia/*drug effects/metabolism MH - NF-kappa B/*metabolism MH - Nitric Oxide/*metabolism MH - Nitric Oxide Synthase Type II/genetics/metabolism OTO - NOTNLM OT - Heme oxygenase-1 OT - Morin OT - Nitric oxide OT - Nuclear factor-kappaB OT - Prostaglandin E(2) EDAT- 2016/05/01 06:00 MHDA- 2017/02/09 06:00 CRDT- 2016/05/01 06:00 PHST- 2016/02/05 00:00 [received] PHST- 2016/04/19 00:00 [revised] PHST- 2016/04/20 00:00 [accepted] PHST- 2016/05/01 06:00 [entrez] PHST- 2016/05/01 06:00 [pubmed] PHST- 2017/02/09 06:00 [medline] AID - S1382-6689(16)30087-4 [pii] AID - 10.1016/j.etap.2016.04.010 [doi] PST - ppublish SO - Environ Toxicol Pharmacol. 2016 Jun;44:62-8. doi: 10.1016/j.etap.2016.04.010. Epub 2016 Apr 22.