6-7-Dimethoxy-4-methylcoumarin suppresses pro-inflammatory mediator expression through inactivation of the NF-κB and MAPK pathways in LPS-induced RAW 264.7 cells

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Kil-Nam Kim
Hye-Won Yang
Seok-Chun Ko
Yeong-Jong Ko
Eun-A Kim
Seong Woon Roh
Eun-Yi Ko
Ginnae Ahn
Soo-Jin Heo
You-Jin Jeon
Weon-Jong Yoon
Chang-Gu Hyun
Daekyung Kim

Abstract

In 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 downregulated 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)-1ß, 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.

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How to Cite
Kim, K.-N., Yang, H.-W., Ko, S.-C., Ko, Y.-J., Kim, E.-A., Roh, S. W., Ko, E.-Y., Ahn, G., Heo, S.-J., Jeon, Y.-J., Yoon, W.-J., Hyun, C.-G., & Kim, D. (2014). 6-7-Dimethoxy-4-methylcoumarin suppresses pro-inflammatory mediator expression through inactivation of the NF-κB and MAPK pathways in LPS-induced RAW 264.7 cells. EXCLI Journal, 13, 792-800. Retrieved from https://www.excli.de/index.php/excli/article/view/741
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