Esculetin suppresses lipopolysaccharide-induced inflammatory mediators and cytokines by inhibiting nuclear factor-κB translocation in RAW 264.7 macrophages

Hong,Su  Hyun; Jeong,Hui-Kyung; Han,Min  Ho; Park,Cheol; Choi,Yung  Hyun

doi:10.3892/mmr.2014.2613

Esculetin suppresses lipopolysaccharide-induced inflammatory mediators and cytokines by inhibiting nuclear factor-κB translocation in RAW 264.7 macrophages

Authors:
- Su Hyun Hong
- Hui-Kyung Jeong
- Min Ho Han
- Cheol Park
- Yung Hyun Choi
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Affiliations: Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, Republic of Korea, Department of Molecular Biology, College of Natural Sciences, Dongeui University, Busan 614-714, Republic of Korea
Published online on: October 8, 2014 https://doi.org/10.3892/mmr.2014.2613
Pages: 3241-3246

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Abstract

Although previous studies have demonstrated that the natural coumarin compound esculetin possesses various pharmacological properties, the molecular mechanism of esculetin-mediated anti-inflammatory potential is not fully understood. In this study, we determined the effects of esculetin on lipopolysaccharide (LPS)-induced inflammatory responses of murine RAW 264.7 macrophages. The results indicate that esculetin inhibits LPS-induced nitric oxide and prostaglandin E2 production in a concentration-dependent manner, and inhibits inducible nitric oxide synthase and cyclooxygenase-2 expression in RAW 264.7 cells. Esculetin also significantly suppresses the production of inflammatory cytokines, including tumor necrosis factor-α and interleukin-1β, which was concomitant with a decrease in their expression levels. Furthermore, it was observed that esculetin attenuated the LPS-mediated nuclear factor-kappa B (NF-κB) translocation associated with the blocking of inhibitor of NF-κB (IκB)-α degradation as well as reactive oxygen species (ROS) production, without any significant cytotoxicity. These data suggest that, by blocking NF-κB activation, esculetin suppresses LPS-elicited inflammatory events, and this is mediated, at least in part, by inhibiting the generation of ROS. Collectively, these findings provide mechanistic insights into the anti-inflammatory action of esculetin in macrophages.

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