6,7-DIMETHOXY-4-METHYLCOUMARIN SUPPRESSES PRO-INFLAMMATORY MEDIATOR EXPRESSION THROUGH INACTIVATION OF THE NF-kappa B AND MAPK PATHWAYS IN LPS-INDUCED RAW 264.7 CELLS

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

来源：EXCLI Journal, 2014, 13: 792-800.

• 6,7-Dimethoxy-4-methylcoumarin (DMC)
• anti-inflammatory
• RAW 264.7 cells
• NF-kappa B
• MAPKs

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 E-2 (PGE(2)) in LPS-activated RAW 264.7 cells. Furthermore, DMC suppressed LPS-induced production of pro-inflammatory cytokines such as interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha. 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-kappa B). 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-kappa B activation via the inhibition of I kappa B-alpha 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-kappa B and MAPK signaling, thereby downregulating the expression of pro-inflammatory mediators.

• 出版日期2014