Anti-inflammatory Activity Screening Essay Of A New Derivant Of Ibuprofen And Preliminary Mechanism Research

Objective:The2-(2-aryhnorpholino)ethyl esters of ibuprofen were synthesized in preliminary study, and the bioassays results indicated that2-(2-arylmorpholino)ethyl esters of compounds have a better activity against COX-2comparing than ibuprofen. Anti-inflammatory properties of ibuprofen are due to its ability to both decrease prostaglandin synthesis by inhibiting the activities of cyclooxygenases (COXs) and IκB kinase-β(IKK-β). However, the anti-inflammatory effects of compounds are not reported. In this study, we investigated whether the2-(2-aryhnorpholino)ethyl esters of ibuprofen have NF-κB inhibition activity in flagellin-induced human monocyte cell line THP-1.Methods:Pretreatment of the THP-1monocyte cells with10μM ibuprofen、compound A and B for1h before flagellin (10ng/ml) cultivation for24h. We observed the expression of TNF-a and IL-1β in culture supernatant and the bind acticity of NF-κB and the level of TLR5inTHP-1cells. The level of TNF-a and IL-1β were detected by ELISA. The activity of NF-κB was measured by EMSA. The level of NF-κB nuclear protein and TLR5protein was measured by western blotting. TLR5mRN A was measured by real-time PCR.Results:Ibuprofen、2-(2-arylmnorphohno)ethyl esters of ibuprofen A and B potently diminished TNF-a and EL-1βat transcriptional level in flagellin-induced THP-1cells. In addition, Ibuprofen、compound A and B attenuated the flagellin-induced the expression and DNA binding activity of NF-κB. Furthermore, Ibuprofen、compound A and B inhibited transcription activity and the level of TLR5mRNA and protein. Taken the preliminary results about the COX-2selective inhibition of compound A and B together, our data indicated that compound A and B are involved the dual inhibition of COX-2and TLR5/NF-κB pathway, revealing molecular basis for the anti-inflammatory properties of A and B.