Inhibition of Prostaglandin Production by a Structurally-Optimized Flavonoid Derivative, 2',4',7-Trimethoxyflavone and Cellular Action Mechanism(Biochemistry)

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概要

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• Flavonoids possess anti-inflammatory activity in vitro and in vivo. In order to find the anti-inflammatory flavone derivatives having optimum chemical structures, various flavones were previously synthesized and evaluated for their inhibitory activity of prostaglandin E_2 (PGE_2) production from lipopolysaccharide (LPS)-treated mouse macrophage cell line, RAW 264.7 cells. Through this screening procedure, 2',4',7-trimethoxyflavone (TMF) was selected for further pharmacological study. From the present investigation, it was found that TMF potently inhibited PGE_2 production from LPS-treated RAW cells with an IC_<50> of 0.48μM, compared to the IC_<50> values of 0.07 and 1.09μM for NS-398 and wogonin. TMF, however, did not inhibit cyclooxygenase-2 (COX-2) activity or COX-2 expression level. Instead, TMF was proved to be a phospholipase A_2 (PLA_2) inhibitor. The IC_<50> values of TMF against secretory PLA_2-IIA (sPLA_2-IIA) and cytosolic PLA_2 (cPLA_2) were 70.5 and 70.4μM, respectively. At doses of 10-250μg/ear, TMF also showed in vivo anti-inflammatory activity by topical application against mouse croton oil-induced ear edema assay, suggesting a potential for new anti-inflammatory agent.

• 公益社団法人日本薬学会の論文
• 2005-08-01

著者

• CHANG Hyeun

  College of Pharmacy, Yeungnam University

• Kim Hyun

  College Of Pharmacy Kangwon National University

• SON Min

  College of Pharmacy, Yeungnam University

• Chang Hyeun

  College Of Pharmacy Yeungnam University

• Han Chang

  Sk Chemicals Ltd.

• Chang Hyeun

  Coll. Of Pharmacy Yeungnam Univ.

• CHI Yeon

  College of Pharmacy, Kangwon National University

• PARK Haeil

  College of Pharmacy, Kangwon National University

• Son Min

  College Of Pharmacy Yeungnam University

• Chi Yeon

  College Of Pharmacy Kangwon National University

• Park Haeil

  College Of Pharmacy Kangwon National University

• Chang H

  College Of Pharmacy Yeungnam University

• Kim Hyun

  College Of Pharmacy And Research Institute Of Drug Development Chonnam National University

• Kim Hyun

  College Of Electrical & Computer Engineering Chungbuk National University

• HAN Chang

  SK Chemical Inc.

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