title: Marine-Derived Secondary Metabolite, Griseusrazin A, Suppresses Inflammation through Heme Oxygenase-1 Induction in Activated RAW264.7 Macrophages.
abstract: A new secondary metabolite, named griseusrazin A (1), was isolated from the marine-derived bacterium Streptomyces griseus subsp. griseus. The structure of the compound was determined by analysis of spectroscopic data including MS, COSY, HSQC, HMBC, and (15)N-HMBC data. Griseusrazin A (1) inhibited the production of inflammatory mediators, such as prostaglandin E2 and nitric oxide, which was mediated through the suppression of the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The production of pro-inflammatory cytokines, such as interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α, in the LPS-stimulated cells was also effectively blocked by griseusrazin A (1). Furthermore, this anti-inflammatory activity of 1 was linked to its inhibitory effects against the nuclear translocation of NF-κB p50 and p65, as wells as NF-κB binding activity. In the further study to elucidate the anti-inflammatory mechanism, 1 was shown to induce heme oxygenase-1 (HO-1) expression through the enhancement of nuclear translocation of nuclear factor E2-related factor 2. Furthermore, the anti-inflammatory activity of 1 in the LPS-stimulated cells was partially reversed by an HO inhibitor, tin protoporphyrin. These results indicate that the anti-inflammatory effect of 1 is associated with Nrf2-mediated HO-1 expression.
authors.affiliation: College of Pharmacy, Wonkwang University , Iksan, 54538, Republic of Korea.|Department of Biomedical Chemistry, College of Health and Biomedical Science, Konkuk University , Chung-Ju 27478, Republic of Korea.
authors.forename: Dong-Sung
authors.initials: DS
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Wonkwang University , Iksan, 54538, Republic of Korea.
authors.forename: Chi-Su
authors.initials: CS
authors.lastname: Yoon
authors.affiliation: Department of Food Science and Biotechnology, Sungkyunkwan University , Jangan-gu, Suwon 16419, Republic of Korea.
authors.forename: Yong-Taek
authors.initials: YT
authors.lastname: Jung
authors.affiliation: Department of Food Science and Biotechnology, Sungkyunkwan University , Jangan-gu, Suwon 16419, Republic of Korea.
authors.forename: Jung-Hoon
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: College of Pharmacy, Wonkwang University , Iksan, 54538, Republic of Korea.
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Wonkwang University , Iksan, 54538, Republic of Korea.
authors.forename: Hyuncheol
authors.initials: H
authors.lastname: Oh
mesh_terms: D000818:Animals; D016207:Cytokines / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D051547:Heme Oxygenase-1 / Q000187:drug effects*; D053583:Interleukin-1beta / Q000187:drug effects; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects; D008386:Marine Biology; D051379:Mice; D015394:Molecular Structure; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects; D019906:Nuclear Magnetic Resonance, Biomolecular; D011719:Pyrazines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects; D013305:Streptomyces griseus / Q000737:chemistry; D051996:Transcription Factor RelA / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011719:Pyrazines; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C000610608:griseusrazin A; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1