title: Esculetin suppresses lipopolysaccharide-induced inflammatory mediators and cytokines by inhibiting nuclear factor-κB translocation in RAW 264.7 macrophages.
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.
authors.affiliation: Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, Republic of Korea.
authors.forename: Su Hyun
authors.initials: SH
authors.lastname: Hong
authors.affiliation: Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, Republic of Korea.
authors.forename: Hui-Kyung
authors.initials: HK
authors.lastname: Jeong
authors.affiliation: Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, Republic of Korea.
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Han
authors.affiliation: Department of Molecular Biology, College of Natural Sciences, Dongeui University, Busan 614-714, Republic of Korea.
authors.forename: Cheol
authors.initials: C
authors.lastname: Park
authors.affiliation: Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, Republic of Korea.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism*; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014468:Umbelliferones / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; C000606205:Nfkbia protein, mouse; D017382:Reactive Oxygen Species; D014468:Umbelliferones; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; D051546:Cyclooxygenase 2; D015232:Dinoprostone; C007628:esculetin