Inhibition of Prostaglandin Production by a Structurally-Optimized Flavonoid Derivative, 2',4',7-Trimethoxyflavone and Cellular Action Mechanism
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- Han Chang Kyun
- SK Chemical Inc.
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- Son Min Jung
- College of Pharmacy, Yeungnam University
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- Chang Hyeun Wook
- College of Pharmacy, Yeungnam University
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- Chi Yeon Sook
- College of Pharmacy, Kangwon National University, Korea
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- Park Haeil
- College of Pharmacy, Kangwon National University, Korea
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- Kim Hyun Pyo
- College of Pharmacy, Kangwon National University, Korea
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Abstract
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 E2 (PGE2) 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 PGE2 production from LPS-treated RAW cells with an IC50 of 0.48 μM, compared to the IC50 values of 0.07 and 1.09 μM 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 A2 (PLA2) inhibitor. The IC50 values of TMF against secretory PLA2-IIA (sPLA2-IIA) and cytosolic PLA2 (cPLA2) were 70.5 and 70.4 μM, respectively. At doses of 10—250 μg/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.
Journal
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- Biological and Pharmaceutical Bulletin
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Biological and Pharmaceutical Bulletin 28 (8), 1366-1370, 2005
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390001204627736576
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- NII Article ID
- 10016666346
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- NII Book ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL BIB ID
- 7372245
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- PubMed
- 16079475
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed