Korean J Physiol Pharmacol.  2016 Jan;20(1):91-99. 10.4196/kjpp.2016.20.1.91.

(E)-3-(3-methoxyphenyl)-1-(2-pyrrolyl)-2-propenone displays suppression of inflammatory responses via inhibition of Src, Syk, and NF-kappaB

Affiliations
  • 1Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Korea. jaecho@skku.edu
  • 2Department of Science Education, Kangwon National University, Chuncheon 24341, Korea. ishl@kangwon.ac.kr
  • 3Department of Bioinformatics and Life Science, Soongsil University, Seoul 06978, Korea. kimmy@ssu.ac.kr

Abstract

(E)-3-(3-methoxyphenyl)-1-(2-pyrrolyl)-2-propenone (MPP) is an aldol condensation product resulting from pyrrole-2-carbaldehyde and m- and p- substituted acetophenones. However, its biological activity has not yet been evaluated. Since it has been reported that some propenone-type compounds display anti-inflammatory activity, we investigated whether MPP could negatively modulate inflammatory responses. To do this, we employed lipopolysaccharide (LPS)-stimulated macrophage-like RAW264.7 cells and examined the inhibitory levels of nitric oxide (NO) production and transcriptional activation, as well as the target proteins involved in the inflammatory signaling cascade. Interestingly, MPP was found to reduce the production of NO in LPS-treated RAW264.7 cells, without causing cytotoxicity. Moreover, this compound suppressed the mRNA levels of inflammatory genes, such as inducible NO synthase (iNOS) and tumor necrosis factor (TNF)-alpha. Using luciferase reporter gene assays performed in HEK293 cells and immunoblotting analysis with nuclear protein fractions, we determined that MPP reduced the transcriptional activation of nuclear factor (NF)-kappaB. Furthermore, the activation of a series of upstream signals for NF-kappaB activation, composed of Src, Syk, Akt, and IkappaBalpha, were also blocked by this compound. It was confirmed that MPP was able to suppress autophosphorylation of overexpressed Src and Syk in HEK293 cells. Therefore, these results suggest that MPP can function as an anti-inflammatory drug with NF-kappaB inhibitory properties via the suppression of Src and Syk.

Keyword

Anti-inflammatory activity; (E)-3-(3-methoxyphenyl)-1-(2-pyrrolyl)-2-propenone; Macrophages; NF-kappaB
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