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Journal of Cellular Biochemistry 2017-Nov

Osajin Inhibits Solar UV-Induced Cyclooxygenase-2 Expression Through Direct Inhibition of RSK2.

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Jong-Eun Kim
Yong-Seok Heo
Ki Won Lee

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요약

Solar ultraviolet light (sUV) has been shown to promote the development of skin disorders including inflammation, photoaging, and skin carcinogenesis. Osajin is the major bioactive isoflavone present in the fruit of Maclura pomifera, commonly referred to as the Osage orange. In this study, we observed that osajin inhibited sUV-induced cyclooxygenase (COX)-2 protein expression in both HaCaT and JB6 cells. COX-2 is a major mediator of skin inflammation. sUV activated the transcription factors nuclear factor-κB and activator protein-1 which, in turn, induces COX-2 expression. Osajin inhibited transactivation of these transcription factors. We identified RSK2 as an inhibitory target of osajin by screening against 68 kinases related to inflammation. Osajin binds with RSK2 directly in an ATP-competitive manner. Computer modeling simulated a plausible binding orientation between osajin and RSK2. Osajin inhibited sUV-induced phosphorylation of histone H3, a substrate of RSK2. However, sUV-induced phosphorylation of extracellular signal-regulated kinases, p38 kinase, c-Jun N-terminal kinase and Akt, which are signaling factors upstream of RSK2, was unchanged in the presence of osajin. The anti-inflammatory effects and molecular mechanism of osajin suggest that it may have utility as a functional food for skin health and cosmetic ingredient. J. Cell. Biochem. 118: 4080-4087, 2017. © 2017 Wiley Periodicals, Inc.

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