Selective inhibition of JAK2/STAT1 signaling and iNOS expression mediates the anti-inflammatory effects of coniferyl aldehyde
- Authors
- Akram, Muhammad; Kim, Kyeong-A; Kim, Eun-Sun; Shin, Young-Jun; Noh, Dabi; Kim, Eunji; Kim, Jeong-Hyeon; Majid, Arshad; Chang, Sun-Young; Kim, Jin-Ki; Bae, Ok-Nam
- Issue Date
- Aug-2016
- Publisher
- ELSEVIER IRELAND LTD
- Keywords
- Coniferyl aldehyde; Anti-inflammatory activity; JAK2-STAT1; Nitric oxide
- Citation
- CHEMICO-BIOLOGICAL INTERACTIONS, v.256, pp.102 - 110
- Indexed
- SCIE
SCOPUS
- Journal Title
- CHEMICO-BIOLOGICAL INTERACTIONS
- Volume
- 256
- Start Page
- 102
- End Page
- 110
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/13094
- DOI
- 10.1016/j.cbi.2016.06.029
- ISSN
- 0009-2797
- Abstract
- Urgent needs still exist for selective control of excessive inflammation. Despite the therapeutic potential of natural compounds against inflammation-associated chronic conditions, lack of specific molecular targets renders these bioactive compounds difficult for further development. Here we examined the bioactivity of coniferyl aldehyde (CA), a natural phenolic compound found in several dietary substances and medicinal plants, elucidating its efficacy both in vivo and in vitro with underlying molecular mechanisms. IFN-gamma/TNF-alpha-stimulated human keratinocytes and lipopolysaccharide (LPS)-stimulated murine macrophages were used to examine the effect of CA in vitro and to elucidate the underlying mechanisms. In vivo models of phorbol 12-myristate 13-acetate (TPA)-induced ear edema and carrageenan (CRG)-induced paw edema were employed to investigate the topical and systemic anti-inflammatory effects of CA, respectively. CA significantly reduced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in LPS-stimulated macrophages. While nuclear factor kappa B (NF-kappa B) and mitogen-activated protein kinase (MAPKs) pathways, the representative cellular pathways for iNOS induction, were not affected by CA, phosphorylation of Janus kinase 2 (JAK2) and signal Transducers and Activators of Transcription 1 (STAT1) and subsequent nuclear translocation of p-STAT1 were significantly decreased by CA. The effect of CA on JAK2-STAT1-iNOS axis was also observed in human keratinocytes stimulated with IFN-gamma/TNF-alpha. Topical application of CA to mice produced significant protection against TPA-induced ear edema along with suppressed epidermal hyperproliferation and leucocyte infiltration. Systemic administration of CA significantly reduced CRG-induced paw edema in rats, where CRG-induced iNOS expression and STAT1 phosphorylation were decreased by CA. In summary, CA has significant anti-inflammatory properties both in vitro and in vivo, mediated by significant selective inhibition of JAK2-STAT1-iNOS signaling. CA is an attractive novel candidate for treating inflammatory diseases associated with excessive production of NO. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
- Files in This Item
-
Go to Link
- Appears in
Collections - COLLEGE OF PHARMACY > DEPARTMENT OF PHARMACY > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/13094)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.