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

Eun Hye Jung, Ji Sun Hwang, Mi Youn Kwon, Kyung Hong Kim, Hyeongjin Cho, In Kyoon Lyoo, Sujeong Shin, Jeong Ho Park, Inn Oc Han

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


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.

Original languageEnglish
Pages (from-to)35-43
Number of pages9
JournalNeurochemistry International
StatePublished - 1 Nov 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Ltd


  • BV2
  • Hybridization
  • Inflammation
  • Tryptamine


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