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Journal of Environmental Pathology, Toxicology and Oncology
Fator do impacto: 1.625 FI de cinco anos: 1.63 SJR: 0.402 SNIP: 0.613 CiteScore™: 2.3

ISSN Imprimir: 0731-8898
ISSN On-line: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.v21.i2.70
8 pages

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

RESUMO

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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