title: 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.
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.
authors.affiliation: Jeju Center, Korea Basic Science Institute (KBSI), Jeju 690-140, Republic of Korea.
authors.forename: Kil-Nam
authors.initials: KN
authors.lastname: Kim
authors.affiliation: School of Marine Biomedical Sciences, Jeju National University, Jeju 690-756, Republic of Korea.
authors.forename: Hye-Won
authors.initials: HW
authors.lastname: Yang
authors.affiliation: School of Marine Biomedical Sciences, Jeju National University, Jeju 690-756, Republic of Korea.
authors.forename: Seok-Chun
authors.initials: SC
authors.lastname: Ko
authors.affiliation: Jeju Biodiversity Research Institute, Jeju Technopark, Jeju 699-943, Republic of Korea.
authors.forename: Yeong-Jong
authors.initials: YJ
authors.lastname: Ko
authors.affiliation: School of Marine Biomedical Sciences, Jeju National University, Jeju 690-756, Republic of Korea.
authors.forename: Eun-A
authors.initials: EA
authors.lastname: Kim
authors.affiliation: Jeju Center, Korea Basic Science Institute (KBSI), Jeju 690-140, Republic of Korea.
authors.forename: Seong Woon
authors.initials: SW
authors.lastname: Roh
authors.affiliation: School of Marine Biomedical Sciences, Jeju National University, Jeju 690-756, Republic of Korea.
authors.forename: Eun-Yi
authors.initials: EY
authors.lastname: Ko
authors.affiliation: Department of Marine Bio-Food Sciences, Chonnam National University, Yeosu 550-749, Republic of Korea.
authors.forename: Ginnae
authors.initials: G
authors.lastname: Ahn
authors.affiliation: Global Bioresources Research Center, Korea Institute of Ocean Science & Technology, Ansan 426-744, Republic of Korea.
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Heo
authors.affiliation: School of Marine Biomedical Sciences, Jeju National University, Jeju 690-756, Republic of Korea.
authors.forename: You-Jin
authors.initials: YJ
authors.lastname: Jeon
authors.affiliation: Jeju Biodiversity Research Institute, Jeju Technopark, Jeju 699-943, Republic of Korea.
authors.forename: Weon-Jong
authors.initials: WJ
authors.lastname: Yoon
authors.affiliation: LINC Agency, Jeju National University, Jeju 690-756, Republic of Korea.
authors.forename: Chang-Gu
authors.initials: CG
authors.lastname: Hyun
authors.affiliation: Jeju Center, Korea Basic Science Institute (KBSI), Jeju 690-140, Republic of Korea.
authors.forename: Daekyung
authors.initials: D
authors.lastname: Kim
keywords: 6,7-Dimethoxy-4-methylcoumarin (DMC); MAPKs; NF-kappaB; RAW 264.7 cells; anti-inflammatory