title: Inhibitory effects of benzaldehyde derivatives from the marine fungus Eurotium sp. SF-5989 on inflammatory mediators via the induction of heme oxygenase-1 in lipopolysaccharide-stimulated RAW264.7 macrophages.
abstract: Two benzaldehyde derivatives, flavoglaucin (1) and isotetrahydro-auroglaucin (2), were isolated from the marine fungus Eurotium sp. SF-5989 through bioassay- and 1H NMR-guided investigation. In this study, we evaluated the anti-inflammatory effects of these compounds in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. We demonstrated that compounds 1 and 2 markedly inhibited LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production by suppressing inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression without affecting cell viability. We also demonstrated that the compounds reduced the secretion of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Furthermore, compounds 1 and 2 inhibited LPS-induced nuclear factor-κB (NF-κB) activation by suppressing phosphorylation of IkappaB (IκB). These results indicated that the anti-inflammatory effects of these benzaldehyde derivatives in LPS-stimulated RAW264.7 macrophages were due to the inactivation of the NF-κB pathway. In addition, compounds 1 and 2 induced heme oxygenase-1 (HO-1) expression through the nuclear transcription factor-E2-related factor 2 (Nrf2) translocation. The inhibitory effects of compounds 1 and 2 on the production of pro-inflammatory mediators and on NF-κB binding activity were reversed by HO-1 inhibitor tin protoporphyrin (SnPP). Thus, the anti-inflammatory effects of compounds 1 and 2 also correlated with their ability of inducing HO-1 expression.
authors.affiliation: College of Pharmacy, Wonkwang University, Iksan 570-749, Korea. pipo5@wku.ac.kr.
authors.forename: Kyoung-Su
authors.initials: KS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Wonkwang University, Iksan 570-749, Korea. loodia@wku.ac.kr.
authors.forename: Xiang
authors.initials: X
authors.lastname: Cui
authors.affiliation: Inha Research Institute for Medical Sciences, Inha University School of Medicine, Incheon 400-712, Korea. dongsunglee@inha.ac.kr.
authors.forename: Dong-Sung
authors.initials: DS
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Wonkwang University, Iksan 570-749, Korea. rabis815@naver.com.
authors.forename: Wonmin
authors.initials: W
authors.lastname: Ko
authors.affiliation: College of Medical and Life Sciences, Silla University, Busan 617-736, Korea. jhsohn@silla.ac.kr.
authors.forename: Jae Hak
authors.initials: JH
authors.lastname: Sohn
authors.affiliation: Korea Polar Research Institute, KORDI, 7-50 Songdo-dong, Yeonsu-gu, Incheon 406-840, Korea. jhyim@kopri.re.kr.
authors.forename: Joung Han
authors.initials: JH
authors.lastname: Yim
authors.affiliation: Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, Yanbian University College of Pharmacy, 977 Gongyuan Road, Yanji 133002, China. anrb@ybu.edu.cn.
authors.forename: Ren-Bo
authors.initials: RB
authors.lastname: An
authors.affiliation: College of Pharmacy, Wonkwang University, Iksan 570-749, Korea. yckim@wku.ac.kr.
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Wonkwang University, Iksan 570-749, Korea. hoh@wku.ac.kr.
authors.forename: Hyuncheol
authors.initials: H
authors.lastname: Oh
mesh_terms: D000818:Animals; D001547:Benzaldehydes / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D055325:Eurotium / Q000737:chemistry*; D005786:Gene Expression Regulation / Q000187:drug effects; D005841:Gentisates / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D001547:Benzaldehydes; D016207:Cytokines; D005841:Gentisates; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D012333:RNA, Messenger; C005001:flavoglaucin; D051547:Heme Oxygenase-1; C032175:benzaldehyde