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7,8-dimethoxycoumarin Attenuates the Expression of IL-6, IL-8, and CCL2/MCP-1 in TNF-α-Treated HaCaT Cells by Potentially Targeting the NF-κB and MAPK Pathways

1
Department of Chemistry and Cosmetics, Jeju National University, Jeju 63243, Korea
2
Jeju Indi Inc., Seogwipo-si, Jeju 63635, Korea
3
R&D Center, CoSeed Bio Pham Co., Chungbuk 28161, Korea
*
Author to whom correspondence should be addressed.
Cosmetics 2019, 6(3), 41; https://doi.org/10.3390/cosmetics6030041
Received: 13 April 2019 / Revised: 4 July 2019 / Accepted: 5 July 2019 / Published: 8 July 2019
(This article belongs to the Special Issue Anti-aging Properties of Natural Compounds)
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Abstract

7,8-dimethoxycoumarin (DMC, C11H10O4), a natural coumarin compound, is present in Citrus plants including Citrus decumana and grapefruit. It is known to have protective effects on the kidneys against Cisplatin and ischemia-reperfusion injury. However, the underlying mechanisms of its inhibitory effects on skin inflammation have not been investigated in vitro. Tumor necrosis factor (TNF)-α is known to be one of the main causative agents of skin inflammation. It induces pro-inflammatory cytokines and chemokines by activating nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling. In this study, we investigated the inhibitory effect of DMC on the expression of pro-inflammatory cytokines and chemokines in TNF-α-treated human keratinocyte HaCaT cells. Pretreatment with DMC inhibited TNF-α-treated cytokines (interleukin 6; IL-6) and chemokines (IL-8 and monocyte chemoattractant protein-1). In addition, DMC significantly inhibited TNF-α-treated NF-κB activation and phosphorylation of MAPKs, such as c-Jun N-terminal kinases (JNK) and extracellular-signal-regulated kinase (ERK). These results suggest that DMC may elicit an anti-inflammatory response by suppressing TNF-α-treated activation of NF-κB and MAPK pathways in keratinocytes. Hence, it might be a useful therapeutic drug against skin inflammatory diseases. View Full-Text
Keywords: 7,8-dimethoxycoumarin; human keratinocyte HaCaT cell; skin inflammation; NF-κB; MAPK 7,8-dimethoxycoumarin; human keratinocyte HaCaT cell; skin inflammation; NF-κB; MAPK
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Lee, N.; Chung, Y.C.; Kang, C.I.; Park, S.-M.; Hyun, C.-G. 7,8-dimethoxycoumarin Attenuates the Expression of IL-6, IL-8, and CCL2/MCP-1 in TNF-α-Treated HaCaT Cells by Potentially Targeting the NF-κB and MAPK Pathways. Cosmetics 2019, 6, 41.

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