Resveratrol 및 그 유도체의 항염증 작용: 새로운 COX-2 및 iNOS 저해제 = Anti-inflammatory Effects of Resveratrol and Its Analogs:COX-2 and iNOS as Potential Targets

다국어 초록 (Multilingual Abstract)

It has been known that resveratrol, a phytoalexin mainly present in grapes, has antioxidant, anti-inflammatory, and cancer chemopreventive activities. One mechanism of its anti-inflammation and cancer prevention is considered to modulate cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) activities. Since COX-2 and iNOS play important roles in inflammation and carcinogenesis, the potential COX-2 and iNOS inhibitors have been considered as anti-inflammatory or cancer chemopreventive agents. In order to discover novel chemopreventive agents, we synthesized about thirty analogs of resveratrol and evaluated their COX-2 and iNOS inhibitory activities with the production of prostaglandin E2 (PGE2) and nitric oxide (NO) in RAW 264.7 cells, respectively. As a result, several compounds exhibited more potent inhibitory activity than resveratrol. Among them, 2-[2-(3,5-dimethoxy-phenyl)-vinyl]-furane which showed inhibitory effects on both PGE2 and NO production was further investigated its mechanism of action on COX-2 and iNOS activities and their expressions. This compound suppressed the lipopolysaccharide (LPS)-induced COX-2 and iNOS protein and mRNA expression. In addition, electrophoretic mobility shift assay (EMSA) study revealed that the suppressions of the COX-2 and iNOS gene expression were related to the inhibition of NF-κB binding activity. Further study exhibited that 2-[2-(3,5-dimethoxy-phenyl)-vinyl]-furane inhibited IκB-α degradation in LPS-stimulated macrophage cells. These findings suggest that 2-[2-(3,5-dimethoxy-phenyl)-vinyl]-furane might be a promising candidate for developing cancer chemopreventive agent. (Cancer Prev Res 10, 116-123, 2005)

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