title: Moracin M inhibits airway inflammation by interrupting the JNK/c-Jun and NF-κB pathways in vitro and in vivo.
abstract: The therapeutic effectiveness of moracins as 2-arylbenzofuran derivatives against airway inflammation was examined. Moracin M, O, and R were isolated from the root barks of Morus alba, and they inhibited interleukin (IL)-6 production from IL-1β-treated lung epithelial cells (A549) at 101-00μM. Among them, moracin M showed the strongest inhibitory effect (IC50=8.1μM). Downregulation of IL-6 expression by moracin M was mediated by interrupting the c-Jun N-terminal kinase (JNK)/c-Jun pathway. Moracin derivatives inhibited inducible nitric oxide synthase (iNOS)-catalyzed NO production from lipopolysaccharide (LPS)-treated alveolar macrophages (MH-S) at 50-100μM. In particular, moracin M inhibited NO production by downregulating iNOS. When orally administered, moracin M (20-60mg/kg) showed comparable inhibitory action with dexamethasone (30mg/kg) against LPS-induced lung inflammation, acute lung injury, in mice with that of dexamethasone (30mg/kg). The action mechanism included interfering with the activation of nuclear transcription factor-κB in inflamed lungs. Therefore, it is concluded that moracin M inhibited airway inflammation in vitro and in vivo, and it has therapeutic potential for treating lung inflammatory disorders.
authors.affiliation: College of Pharmacy, Kangwon National University, Chunchon 24341, Republic of Korea.
authors.forename: Ju Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Chosun University, Kwangjoo 61452, Republic of Korea.
authors.forename: Hae Ju
authors.initials: HJ
authors.lastname: Ko
authors.affiliation: College of Pharmacy, Chosun University, Kwangjoo 61452, Republic of Korea.
authors.forename: Eun-Rhan
authors.initials: ER
authors.lastname: Woo
authors.affiliation: College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Sang Kook
authors.initials: SK
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Kangwon National University, Chunchon 24341, Republic of Korea.
authors.forename: Bong Soo
authors.initials: BS
authors.lastname: Moon
authors.affiliation: College of Pharmacy, Kangwon National University, Chunchon 24341, Republic of Korea.
authors.forename: Chan Woo
authors.initials: CW
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Kangwon National University, Chunchon 24341, Republic of Korea.
authors.forename: Suresh
authors.initials: S
authors.lastname: Mandava
authors.affiliation: College of Pharmacy, Kangwon National University, Chunchon 24341, Republic of Korea.
authors.forename: Mallesham
authors.initials: M
authors.lastname: Samala
authors.affiliation: College of Pharmacy, Kangwon National University, Chunchon 24341, Republic of Korea.
authors.forename: Jongkook
authors.initials: J
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Kangwon National University, Chunchon 24341, Republic of Korea. Electronic address: hpkim@kangwon.ac.kr.
authors.forename: Hyun Pyo
authors.initials: HP
authors.lastname: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001572:Benzofurans / Q000494:pharmacology* / Q000627:therapeutic use; D055162:Biocatalysis / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D012118:Resorcinols / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000893:Anti-Inflammatory Agents; D001572:Benzofurans; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D012118:Resorcinols; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D048031:JNK Mitogen-Activated Protein Kinases; C568020:moracin M
keywords: A549; Airway inflammation; Arylbenzofuran; Moracin; Moracin M (PubChem CID: 185848); Moracin O (PubChem CID: 14539883); Moracin R (PubChem CID: 42605183); Morus alba