title: A tryptamine-paeonol hybridization compound inhibits LPS-mediated inflammation in BV2 cells.
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.
authors: Department of Physiology and Biophysics, College of Medicine, Inha University, Incheon, South Korea.
authors: Eun-Hye
authors: EH
authors: Jung
authors: Department of Physiology and Biophysics, College of Medicine, Inha University, Incheon, South Korea.
authors: Ji-Sun
authors: JS
authors: Hwang
authors: Department of Physiology and Biophysics, College of Medicine, Inha University, Incheon, South Korea.
authors: Mi-Youn
authors: MY
authors: Kwon
authors: Department of Physiology and Biophysics, College of Medicine, Inha University, Incheon, South Korea.
authors: Kyung-Hong
authors: KH
authors: Kim
authors: Department of Chemistry, Inha University, Incheon, South Korea.
authors: Hyeongjin
authors: H
authors: Cho
authors: Ewha Brain Institute, Department of Brain and Cognitive Sciences, College of Pharmacy, Ewha Womans University, Seoul, South Korea.
authors: In Kyoon
authors: IK
authors: Lyoo
authors: Department of Chemical & Biological Engineering, Hanbat National University, Daejeon, South Korea.
authors: Sujeong
authors: S
authors: Shin
authors: Department of Chemical & Biological Engineering, Hanbat National University, Daejeon, South Korea.
authors: Jeong-Ho
authors: JH
authors: Park
authors: Department of Physiology and Biophysics, College of Medicine, Inha University, Incheon, South Korea. Electronic address: iohan@inha.ac.kr.
authors: Inn-Oc
authors: IO
authors: Han
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014363:Tryptamines / Q000494:pharmacology*
chemical_list: D000098:Acetophenones; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014363:Tryptamines; D009569:Nitric Oxide; C013638:paeonol; C030820:tryptamine; D051546:Cyclooxygenase 2
keywords: BV2; Hybridization; Inflammation; Tryptamine