A tryptamine-paeonol hybridization compound inhibits LPS-mediated inflammation in BV2 cells. (November 2016)

• Record Type: Journal Article
• Authors: Jung, Eun-Hye; Hwang, Ji-Sun; Kwon, Mi-Youn; Kim, Kyung-Hong; Cho, Hyeongjin; Lyoo, In Kyoon; Shin, Sujeong; Park, Jeong-Ho; Han, Inn-Oc
• Is Part Of: Neurochemistry international. Volume 100(2016)
• Page Start: 35
• Page End: 43
• Publication Date: 2016-11
• Subjects: Tryptamine -- Hybridization -- Inflammation -- BV2; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2016.08.010
• Languages: English
• ISSNs: 0197-0186

Abstract

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. Highlights: Tryptamine and paeonol hybridization compound (HBU-376 ) was synthesized. HBU-376 inhibited LPS-induced inflammation in BV2 cells. HBU-376 inhibited LPS-induced STAT-3 phosphorylation. HBU-376 inhibited LPS-induced NF-kappaB activation. HBU-376 may be therapeutic agent for inflammatory diseases of CNS.