Moracin M inhibits airway inflammation by interrupting the JNK/c-Jun and NF-κB pathways in vitro and in vivo

  • Eur J Pharmacol. 2016 Jul 15:783:64-72. doi: 10.1016/j.ejphar.2016.04.055.
Ju Hee Lee  1 ,  Hae Ju Ko  2 ,  Eun-Rhan Woo  2 ,  Sang Kook Lee  3 ,  Bong Soo Moon  1 ,  Chan Woo Lee  1 ,  Suresh Mandava  1 ,  Mallesham Samala  1 ,  Jongkook Lee  1 ,  Hyun Pyo Kim  4
Affiliations
  • 1. College of Pharmacy, Kangwon National University, Chunchon 24341, Republic of Korea.
  • 2. College of Pharmacy, Chosun University, Kwangjoo 61452, Republic of Korea.
  • 3. College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
  • 4. College of Pharmacy, Kangwon National University, Chunchon 24341, Republic of Korea. Electronic address: [email protected].
PMID: 27138708 DOI: 10.1016/j.ejphar.2016.04.055
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.

Keywords
A549; Airway inflammation; Arylbenzofuran; Moracin; Moracin M (PubChem CID: 185848); Moracin O (PubChem CID: 14539883); Moracin R (PubChem CID: 42605183); Morus alba.
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