title: A novel caffeic acid-1-piperonylpiperazine hybridization compound HBU-47 inhibits LPS-mediated inflammation in RAW264.7 macrophage cells.
abstract: In the present study, we synthesized a new hybrid compound by coupling caffeic acid and 1-piperonylpiperazine. The synthetic compound, acetyl-caffeic acid-1-piperonylpiperazine (HBU-47), showed potent anti-inflammatory effects inhibiting lipopolysaccharide (LPS)-induced production of nitric oxide (NO) in RAW264.7 macrophage cells. HBU-47 inhibited LPS-caused induction of inducible NO synthase (iNOS), cyclooxygenase-2, interleukin-6 and interleukin-1β in RAW264.7 cells in time- and dose-dependent manner. Compared to HBU-47, neither caffeic acid nor 1-piperonylpiperazine displayed significant inhibition of LPS responses. HBU-47 did not affect LPS-caused activation of mitogen-activated kinases (MAPKs) or IκB-α degradation. Instead, LPS-mediated NF-κB activation and DNA bindings of p65, p50 and c-Rel to the NF-κB binding site of iNOS promoter were inhibited by HBU-47. Overall, our data suggest that the novel caffeic acid hybrid compound downregulates inflammatory responses through inhibition of NF-κB and NF-κB-dependent gene expressions, thus, further suggesting its efficacy as a promising therapeutic agent.
authors.affiliation: Department of Physiology and Biophysics, Inha University, College of Medicine, Incheon, South Korea.
authors.forename: Seon-Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Physiology and Biophysics, Inha University, College of Medicine, Incheon, South Korea.
authors.forename: Ji-Sun
authors.initials: JS
authors.lastname: Hwang
authors.affiliation: Department of Chemical & Biological Engineering, Hanbat National University, Dongseodaero 125, Dukmyung-Dong, Yuseong-Gu, Daejeon 305-719, South Korea.
authors.forename: Mi
authors.initials: M
authors.lastname: Jang
authors.affiliation: Department of Chemical & Biological Engineering, Hanbat National University, Dongseodaero 125, Dukmyung-Dong, Yuseong-Gu, Daejeon 305-719, South Korea.
authors.forename: Seung Hwan
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Chemical & Biological Engineering, Hanbat National University, Dongseodaero 125, Dukmyung-Dong, Yuseong-Gu, Daejeon 305-719, South Korea.
authors.forename: Jeong-Ho
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Physiology and Biophysics, Inha University, College of Medicine, Incheon, South Korea. Electronic address: iohan@inha.ac.kr.
authors.forename: Inn-Oc
authors.initials: IO
authors.lastname: Han
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002109:Caffeic Acids / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics; D009573:Nitrites / Q000276:immunology; D010879:Piperazines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D002109:Caffeic Acids; D052246:Cyclooxygenase 2 Inhibitors; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009573:Nitrites; D010879:Piperazines; D012333:RNA, Messenger; C000592485:acetyl-caffeic acid-1-piperonylpiperazine; C078092:1-piperonylpiperazine; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C040048:caffeic acid
keywords: 1-Piperonylpiperazine; Caffeic acid; Inflammation