Fraxinellone Inhibits Lipopolysaccharide-Induced Inducible Nitric Oxide Synthase and Cyclooxygenase-2 Expression by Negatively Regulating Nuclear Factor-kappa B in RAW 264.7 Macrophages Cells
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概要
- 論文の詳細を見る
Fraxinellone is formed by the natural degradation of limonoids isolated from the root bark of Dictamnus dasycarpus. Fraxinellone has been reported to possess neuroprotective and vasorelaxing activities, but the effects and the mechanism of fraxinellone in inflammation have not been fully characterized. In the present study, the anti-inflammatory effect of fraxinellone was evaluated in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Fraxinellone was found to inhibit LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production, and to reduce the LPS-induced expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the mRNA and protein levels in a dose-dependent manner. Furthermore, fraxinellone significantly attenuated LPS-induced DNA binding activity and the transcription activity of nuclear factor-kappa B (NF-κB). Consistent with these findings, pretreatment with fraxinellone significantly suppressed the LPS-stimulated phosphorylation of inhibitory kappa B-α (IκB-α) and the subsequent translocation of p65 to the nucleus. Fraxinellone also suppressed the IκB kinase (IKK) activity and the phosphorylation of extracellular-signal-related kinase (ERK1/2), whereas the phosphorylations of Jun N-terminal kinase (JNK1/2) and p38 were unaffected. These results suggest that the anti-inflammatory properties of fraxinellone are related to the down-regulations of iNOS and COX-2 due to NF-κB inhibition through the negative regulations of IKK and ERK1/2 phosphorylations in RAW 264.7 cells.
- 公益社団法人 日本薬学会の論文
著者
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PARK Hee-Juhn
Department of Botanical Resources, Sangji University
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Park Yeong-min
Dep. Of Microbiology And Immunology Pusan National Univ. Coll. Of Medicine
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Park Yeong-min
Dep. Of Microbiology And Immunology And National Res. Lab. Of Dendritic Cell Differentiation & R
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Lee Kyung-tae
Department Of Life And Nanopharmaceutical Sciences College Of Pharmacy Kyung Hee University
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Lee Kyung-tae
Department Of Biochemistry College Of Pharmacy Kyung Hee University
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Park Hee-juhn
Department Of Botanical Resources Sangi University
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PARK Young-Mi
Department of Biochemistry, College of Pharmacy, Kyung-Hee University
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JUNG Hyun-Ju
Department of Botanical Resources, Sangji University
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KIM Jong-Hwan
Department of Gynecology, School of Oriental Medicine, Wonkwang University
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Park Seung
Department Of Medicine Samsung Medical Center Sungkyunkwan University School Of Medicine
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Choi Jung-hye
Department Of Internal Medicine Hanyang University
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Park Yeong-min
Department Of Microbiology & Immunology And National Research Laboratory Of Dendritic Cell Diffe
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Park Seung
Department Of Anatomy Wonkwang University School Of Medicine
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Shin Ji-Sun
Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung-Hee University
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Kim Jong-hwan
Department Of Electrical And Electronic Engineering College Of Engineering Yonsei University
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Park Young-mi
Department Of Microbiology And Immunology And National Research Laboratory Of Dendritic Cell Differe
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Shin Ji-sun
Department Of Pediatric Dentistry Dental Hospital Dankook University
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Park Seung
Department Of Anatomy College Of Medicine Konkuk University
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Park Young-Mi
Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung-Hee University
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Lee Kyung-Tae
Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung-Hee University
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Jung Hyun-Ju
Department of Oriental Pharmacy, Wonkwang University
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Kim Jong-Hwan
Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung-Hee University
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Choi Jung-Hye
Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung-Hee University
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Kim Jong-Hwan
Department of Electrical & Electronic Engineering, College of Engineering, Yonsei University, 134 Shinchon-dong, Seodaemoon-ku, Seoul 120-749, Korea
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