A novel caffeic acid–1-piperonylpiperazine hybridization compound HBU-47 inhibits LPS-mediated inflammation in RAW264.7 macrophage cells

• HBU-47 was synthesized by coupling caffeic acid and 1-piperonylpiperazine.
• HBU-47 inhibited LPS-induced production of NO in RAW264.7 cells.
• Neither caffeic acid nor 1-piperonylpiperazine inhibited LPS responses.
• HBU-47 did not affect LPS-caused activation of MAPKs or IκB-α degradation.
• HBU-47 inhibited LPS-mediated NF-κB activation.

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.