Journal of Applied Biological Chemistry

The Korean Society for Applied Biological Chemistry (한국응용생명화학회)
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The hyaluronan synthesis inhibitor 7-hydroxy-4-methylcoumarin inhibits LPS-induced inflammatory response in RAW 264.7 macrophage cells

  • Kim, Gwan Bo (Jeju Inside Agency and Cosmetic Science Center, Department of Chemistry and Cosmetics, Jeju National University) ;
  • Hyun, Chang-Gu (Jeju Inside Agency and Cosmetic Science Center, Department of Chemistry and Cosmetics, Jeju National University)
  • Received : 2021.07.21
  • Accepted : 2021.07.29
  • Published : 2021.09.30
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Abstract

7-Hydroxy-4-methylcoumarin (7H-4MC) inhibits hyaluronan production in multiple cell lines and tissue types both in vitro and in vivo. It is a commercially available drug approved for human use, called hymecromone, in European and Asian countries to prevent biliary spasms. Nevertheless, as the pharmacological efficacy of 7H-4MC has not yet been reported in macrophages, this study investigated its anti-inflammatory effects and mechanism of action using lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. LPS-induced RAW 264.7 cells were treated with various concentrations of 7H-4MC (62.5, 125, 250, and 500 μM). The application of 7H-4MC significantly reduced nitric oxide and prostaglandin E2 production without cytotoxic effects. Additionally, 7H-4MC strongly decreased the expression of inducible nitric oxide synthase and cyclooxygenase. Furthermore, 7H-4MC reduced the production of proinflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. Finally, 7H-4MC exerted its potent anti-inflammatory actions via the upregulation of IκB-α production, which led to the inhibition of nuclear factor-κB (NF-κB) activity. These results, obtained in macrophage cell lines, suggest that 7H-4MC prevents inflammatory diseases via the NF-κB signaling pathway and that its use could be beneficial for human health. Ultimately, this is the first report describing the anti-inflammatory activity of 7H-4MC in a macrophage cell line.

Keywords

Acknowledgement

The authors thank all the students in our research group for their helpful cooperation and discussions. This research was supported by the Ministry of Trade, Industry & Energy (MOTIE), Korea Institute for Advancement of Technology (KIAT) through the Encouragement Program for the Industries of Economic Cooperation Region (P0006063).

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