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Ethanol Extract of Ligularia fischeri Inhibits the Lipopolysaccharide-Induced Inflammatory Response by Exerting Anti-Histone Acetyltransferase Activity to Negatively Regulate p65

Journal of Medicinal Food 2019년 22권 11호 p.1127 ~ 1135
김효진, 최호경, 정민유, 박재호, 정상원, 이승현, 황진택,
소속 상세정보
김효진 ( Kim Hyo-Jin ) - Korea Food Research Institute
최호경 ( Choi Hyo-Kyoung ) - Korea Food Research Institute
정민유 ( Chung Min-Yu ) - Korea Food Research Institute
박재호 ( Park Jae-Ho ) - Korea Food Research Institute
정상원 ( Chung Sang-Won ) - Korea Food Research Institute
이승현 ( Lee Seung-Hyun ) - Yonsei University College of Medicine Department of Biochemistry and Molecular Biology
황진택 ( Hwang Jin-Taek ) - Korea Food Research Institute

Abstract


Histone acetyltransferase (HAT) activity is well established to regulate inflammatory responses. In contrast, the mechanisms by which natural nutritional extracts influence epigenetic mechanisms to regulate inflammation have not yet been thoroughly investigated. Thus, in the present study, we observed that the anti-HAT activity exerted by an ethanol extract of Ligularia fischeri (ELF) inhibited inflammation. Specifically, we used a cell-free system to show that ELF attenuates HAT activity. We also demonstrated that ELF decreases lipopolysaccharide (LPS)-induced HAT mRNA and protein expression levels in Raw 264.7 cells, and thereby attenuates inflammation-induced patterns of hyperacetylation at nonhistone and histone-H4 proteins. Interestingly, we found that ELF blocked p65 translocation in LPS-stimulated Raw 264.7 cells by attenuating acetylation at lysine residue 310 of p65. Finally, we investigated whether ELF reduces the inflammatory cytokines, IL-6, IL-1β, and TNFα, using its HAT inhibitor activity. Taken together, these results suggest that ELF negatively regulates inflammatory responses by inhibiting HATs and HAT activity.

키워드

histone acetyltransferase; inflammation; Ligularia fischeri; p65; Raw 264.7 cells

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