抄録
Nitric oxide (NO) is an important cellular signaling molecule in inflammatory diseases. It is synthesized from L-arginine by a specific enzyme, NO synthase (NOS) that is composed three types, endothelial NOS (eNOS), neuronal NOS (nNOS), and inducible NOS (iNOS). Among them, iNOS is activated by various stimuli such as lipopolysaccharide (LPS), a wall component of gram-negative bacteria, in macrophage. LPS binds a TLR4 on the macrophage and activates a down-stream of TLR4 signaling pathway, including mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB pathways. Sargaquinoic acid isolated from S. siliquastrum is known to have various activities, except anti-inflammatory activity. In this study, we investigated the effect of sargaquinoic acid on NO production and the possible mechanism. The results demonstrated that sargaquinoic acid inhibited the production of NO and the expression of iNOS protein in LPS-stimulated RAW264.7 macrophages. Moreover, sargaquinoic acid inhibited the degradation of IκB-α and the translocation of NF-κB, a key transcription factor for regulation of iNOS expression. However, sargaquinoic acid did not influence on the phosphorylation of MAPKs or STAT signaling pathway by LPS-stimulation. These results suggest that sargaquinoic acid specifically prevents NO production in macrophages via the blockade of NF-κB activation and may thus have therapeutic applications in various inflammatory diseases.
Keywords: Sargaquinoic acid, Inflammation, Nitric Oxide, Nuclear factor-κB, RAW264.7 macrophage
