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Journal of Environmental Pathology, Toxicology and Oncology

 

ISSN for PRINT: 0731-8898

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$672.00

Issues per year:

4

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2002, Volume21

Issue 2

  124 pages  

   

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Issue price - $160.00  

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  • Suppressive Effect of Natural Sesquiterpenoids on Inducible Cyclooxygenase (COX-2) and Nitric Oxide Synthase (iNOS) Activity in Mouse Macrophage Cells
  • Sang Kook Lee
    College of Pharmacy, EwhaWomans University, Seoul, Korea

    Chai-Hee Hong
    College of Pharmacy, EwhaWomans University, Seoul, Korea

    Sun-Kyung Huh
    College of Pharmacy, Ewha Womans University, Seoul, Korea

    Sun-Sook Kim
    College of Pharmacy, Ewha Womans University, Seoul, Korea

    O-Jin Oh
    College of Pharmacy, Ewha Womans University, Seoul, Korea

    Hye-Young Min
    College of Pharmacy, Ewha Womans University, Seoul, Korea

    Kwang-Kyun Park
    College of Dental Medicine, Yonsei University, Seoul, Korea

    Won-Yoon Chung
    College of Dental Medicine, Yonsei University, Seoul, Korea

    Jae-Kwan Hwang
    Bioproducts Research Center, Yonsei University, Seoul, Korea


    ABSTRACT

    Prostaglandins and nitric oxide produced by inducible cyclooygenase (COX-2) and nitric oxide synthase (iNOS), respectively, have been implicated as important mediators in the processes of inflammation and carcinogenesis. These potential COX-2 and iNOS inhibitors have been considered as antiinflammatory and cancer chemopreventive agents. In this study, we investigated the effect of natural Sesquiterpenoids isolated from plants of the Zingiberaceae family on the activities of COX-2 and iNOS in cultured lipopolysaccharide (LPS)-activated mouse macrophage cell RAW 264.7 to discover new lead compounds as COX-2 or iNOS inhibitors. Xanthorrhizol, a sesquiterpenoid, isolated from the rhizome of Curcuma xanthorrhiza Roxb. (Zingiberaceae), exhibited a potent inhibition of COX-2 (IC50 = 0.2 g/mL) and iNOS activity (IC50 = 1.0 g/mL) in the assay system of prostaglandin E2 (PGE2) accumulation and nitric oxide production, respectively. Western blot analyses revealed that the inhibitory potential of xanthorrhizol on the COX-2 activity coincided well with the suppression of COX-2 protein expression in LPS-induced macrophages. In addition, Sesquiterpenoids b-turmerone and ar-turmerone isolated from the rhizome of Curcuma zedoaria Roscoe (Zingiberaceae) also showed a potent inhibitory activity of COX-2 (b-turmerone, IC50 = 1.6 mg/mL; ar-turmerone, IC50 = 5.2 mg/mL) and iNOS (b-turmerone, IC50 = 4.6 mg/mL; ar-turmerone, IC50 = 3.2 mg/mL). These results suggest that natural sesquiterpenoids from C. xanthorrhiza and C. zedoariu might be lead candidates for further developing COX-2 or iNOS inhibitors possessing cancer chemopreventive or anti-inflammatory properties.

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