Anti-inflammatory Activity of the Synthetic Chalcone Derivatives : Inhibition of Inducible Nitric Oxide Synthase-Catalyzed Nitric Oxide Production from Lipopolysaccharide-Treated RAW 264.7 Cells(Pharmacology)
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概要
- 論文の詳細を見る
Chalcones belong to the flavonoid family from plant origin and some of them possess anti-inflammatory activity. Recently, several natural and synthetic chalcone derivatives were reported to inhibit inducible nitric oxide synthase (iNOS)-catalyzed NO production in cell cultures. In the present study, to find the optimal chemical structures and to elucidate their action mechanisms, 41 synthetic chalcones having the substituent(s) on A- and B-rings were prepared and their effects on iNOS-catalyzed NO production were evaluated using lipopolysaccharide (LPS)-treated RAW 264.7 cells. When simultaneously added with LPS, 2'-methoxy-3,4-dichlorochalcone (Ch15), 2'-hydroxy-6'-methoxychalcone (Ch29), 2'-hydroxy-3-bromo-6'-methoxychalcone (Ch31) and 2'-hydroxy-4',6'-dimethoxychalcone (Ch35) among the tested compounds potently inhibited NO production (IC_<50>s, 7.1-9.6 μM). The favorable chemical structures were found to be a methoxyl substitution in A-ring at an adjacent position (2' or 6') to carbonyl moiety with/without 2'-(or 6'-)hydroxyl group and 3-halogen substitution in B-ring. When the cellular action mechanisms of Ch15, Ch31 and Ch35 were further examined using Western blotting and electrophoretic mobility shift assay, it was revealed that Ch15 and Ch31 clearly down-regulated iNOS expression while Ch35 did not. Moreover, Ch15 and Ch31 were proved to suppress the nuclear transcription factor-kB activation. From the results, it is suggested that certain chalcone derivatives potently inhibit iNOS-catalyzed NO production by the different cellular mechanisms, iNOS down-regulation and/or iNOS inhibition, depending on their chemical structures. These chalcone derivatives may possibly be used as lead compounds for developing new anti-inflammatory agents.
- 公益社団法人日本薬学会の論文
- 2007-08-01
著者
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Kim Young
College of Pharmacy, Chungnam National University
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Kim Hyun
College Of Pharmacy Kangwon National University
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Kim Young
College Of Pharmacy Kangwon National University
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PARK Haeil
College of Pharmacy, Kangwon National University
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Kim Young
College Of Pharmacy And Research Institute Of Pharmaceutical Science Seoul National University
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Park Haeil
College Of Pharmacy Kangwon National University
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KIM Jeongsoo
College of Pharmacy, Kangwon National University
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Kim Hyun
College Of Pharmacy And Research Institute Of Drug Development Chonnam National University
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Kim Jeongsoo
College Of Pharmacy Kangwon National University
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Kim Hyun
College Of Electrical & Computer Engineering Chungbuk National University
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Kim Hyun
Coll. Of Pharmacy Kangwon National Univ. Kor
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Kim Young
Colledge of Pharmacy, Wonkwang University
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