Kim, Kil-NamYang, Hye-WonKo, Seok-ChunKo, Yeong-JongKim, Eun-ARoh, Seong WoonKo, Eun-YiAhn, GinnaeHeo, Soo-JinJeon, You-JinYoon, Weon-JongHyun, Chang-GuKim, Daekyung2014-11-252014-11-252014-07-211611-2156http://hdl.handle.net/2003/3371210.17877/DE290R-6945In this study, we investigated the ability of 6,7-dimethoxy-4-methylcoumarin (DMC) to inhibit lipopolysaccharide (LPS)-induced expression of pro-inflammatory mediators in mouse macrophage (RAW 264.7) cells, and the molecular mechanism through which this inhibition occurred. Our results indicated that DMC down regulated LPS-induced nitric oxide (NO) synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, thereby reducing the production of NO and prostaglandin E2 (PGE2) in LPS-activated RAW 264.7 cells. Furthermore, DMC suppressed LPS-induced production of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. To elucidate the mechanism underlying the anti- inflammatory activity of DMC, we assessed its effects on the mitogen-activated protein kinase (MAPK) pathway and the activity and expression of nuclear transcription factor kappa-B (NF-κB). The experiments demonstrated that DMC inhibited LPS-induced phosphorylation of extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinase (JNK), and p38. In addition, it attenuated LPS-induced NF-κB activation via the inhibition of IκB-α phosphorylation. Taken together, these data suggest that DMC exerts its anti-inflammatory effects in RAW 264.7 cells through the inhibition of LPS-stimulated NF-κB and MAPK signaling, thereby downregulating the expression of pro-inflammatory mediators.enEXCLI Journal ; Vol. 13, 20146,7-Dimethoxy-4-methylcoumarin (DMC)anti-inflammatoryRAW 264.7 cellsNF-κBMAPKs610article (journal)