Pyrrole-Derivative of Chalcone, (E)-3-Phenyl-1-(2-Pyrrolyl)-2-Propenone, Inhibits Inflammatory Responses via Inhibition of Src, Syk, and TAK1 Kinase Activities
- Authors
- Yang, S[Yang, Sungjae]; Kim, Y[Kim, Yong]; Jeong, D[Jeong, Deok]; Kim, JH[Kim, Jun Ho]; Kim, S[Kim, Sunggyu]; Son, YJ[Son, Young-Jin]; Yoo, BC[Yoo, Byong Chul]; Jeong, EJ[Jeong, Eun Jeong]; Kim, TW[Kim, Tae Woong]; Lee, ISH[Lee, In-Sook Han]; Cho, JY[Cho, Jae Youl]
- Issue Date
- 1-Nov-2016
- Publisher
- KOREAN SOC APPLIED PHARMACOLOGY
- Keywords
- Pyrrole; Chalcone; Anti-inflammatory activity; Macrophages; NF-kappa B
- Citation
- BIOMOLECULES & THERAPEUTICS, v.24, no.6, pp.595 - 603
- Indexed
- SCIE
SCOPUS
KCI
- Journal Title
- BIOMOLECULES & THERAPEUTICS
- Volume
- 24
- Number
- 6
- Start Page
- 595
- End Page
- 603
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/34407
- DOI
- 10.4062/biomolther.2016.027
- ISSN
- 1976-9148
- Abstract
- (E)-3-Phenyl-1-(2-pyrrolyl)-2-propenone (PPP) is a pyrrole derivative of chalcone, in which the B-ring of chalcone linked to beta-carbon is replaced by pyrrole group. While pyrrole has been studied for possible Src inhibition activity, chalcone, especially the substituents on the B-ring, has shown pharmaceutical, anti-inflammatory, and anti-oxidant properties via inhibition of NF-kappa B activity. Our study is aimed to investigate whether this novel synthetic compound retains or enhances the pharmaceutically beneficial activities from the both structures. For this purpose, inflammatory responses of lipopolysaccharide (LPS)-treated RAW264.7 cells were analyzed. Nitric oxide (NO) production, inducible NO synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha) mRNA expression, and the intracellular inflammatory signaling cascade were measured. Interestingly, PPP strongly inhibited NO release in a dose-dependent manner. To further investigate this anti-inflammatory activity, we identified molecular pathways by immunoblot analyses of nuclear fractions and whole cell lysates prepared from LPS-stimulated RAW264.7 cells with or without PPP pretreatment. The nuclear levels of p50, c-Jun, and c-Fos were significantly inhibited when cells were exposed to PPP. Moreover, according to the luciferase reporter gene assay after cotransfection with either TRIF or MyD88 in HEK293 cells, NF-kappa B-mediated luciferase activity dose-dependently diminished. Additionally, it was confirmed that PPP dampens the upstream signaling cascade of NF-kappa B and AP-1 activation. Thus, PPP inhibited Syk, Src, and TAK1 activities induced by LPS or induced by overexpression of these genes. Therefore, our results suggest that PPP displays anti-inflammatory activity via inhibition of Syk, Src, and TAK1 activity, which may be developed as a novel anti-inflammatory drug.
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- Appears in
Collections - Biotechnology and Bioengineering > Integrative Biotechnology > 1. Journal Articles
- OTHERS > ETC > 1. Journal Articles
- Biotechnology and Bioengineering > Department of Genetic Engineering > 1. Journal Articles
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