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A tryptamine-paeonol hybridization compound inhibits LPS-mediated inflammation in BV2 cells

Title
A tryptamine-paeonol hybridization compound inhibits LPS-mediated inflammation in BV2 cells
Authors
Jung E.-H.Hwang J.-S.Kwon M.-Y.Kim K.-H.Cho H.Lyoo I.K.Shin S.Park J.-H.Han I.-O.
Ewha Authors
류인균
SCOPUS Author ID
류인균scopus
Issue Date
2016
Journal Title
Neurochemistry International
ISSN
0197-0186JCR Link
Citation
vol. 100, pp. 35 - 43
Keywords
BV2HybridizationInflammationTryptamine
Publisher
Elsevier Ltd
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
In the present study, we synthesized and evaluated the anti-inflammatory effects of three tryptamine (Trm) hybrid compounds, HBU-375, HBU-376 and HBU-379. The Click reaction between the azido-Trm and 2- or 4-propazylated paeonol moiety resulted in HBU-376 and HBU-375, respectively. HBU-379 was generated by hybridizing Trm with propazylated acetyl-syringic acid. HBU-376 and HBU-375 dose-dependently inhibited LPS and caused nitric oxide (NO) generation in BV2 cells, whereas HBU-379 minimally inhibited NO generation, indicating that the paeonol unit plays an important role in the anti-inflammatory effect of Trm hybrid compounds. Although HBU-375 and HBU-376 demonstrated a similar inhibitory effect on LPS-induced NO generation, HBU-376 resulted in less cellular toxicity presumably due to the free phenolic hydroxyl group of paeonol. Therefore, HBU-376 may be a promising anti-inflammatory agent conferring minimal cytotoxicity. HBU-376 significantly and dose-dependently inhibited LPS-induced NO products, NO synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6, MCP-1 and interleukin-1β mRNA expressions and iNOS and COX-2 protein expressions. However, at the same concentrations, Trm or paeonol individually did not inhibit LPS-mediated production of inflammatory molecules. HBU-376 inhibited both LPS-induced STAT-3 phosphorylation and nuclear factor-kappa B (NF-κB) activation. Furthermore, LPS-mediated DNA binding of c-Rel, p50 and p52 to the NF-κB binding site of the iNOS promoter was inhibited by HBU-376, whereas Trm and paeonol did not inhibit LPS-induced NF-κB activation and DNA binding of c-Rel, p50 and p52. Overall, our data suggest that the Trm-paeonol hybrid compound down-regulates inflammatory responses by inhibiting NF-κB and NF-κB-dependent gene expression. This suggests that it is a potential therapeutic agent for inflammatory diseases of the central nervous system. © 2016 Elsevier Ltd
DOI
10.1016/j.neuint.2016.08.010
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약학대학 > 약학과 > Journal papers
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