title: Suppressive effect of natural sesquiterpenoids on inducible cyclooxygenase (COX-2) and nitric oxide synthase (iNOS) activity in mouse macrophage cells.
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 microg/mL) and iNOS activity (IC50 = 1.0 microg/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 beta-turmerone and ar-turmerone isolated from the rhizome of Curcuma zedoaria Roscoe (Zingiberaceae) also showed a potent inhibitory activity of COX-2 (beta-turmerone, IC50 = 1.6 microg/mL; ar-turmerone, IC50 = 5.2 microg/mL) and iNOS (beta-turmerone, IC50 = 4.6 microg/mL; ar-turmerone, IC50 = 3.2 microg/mL). These results suggest that natural sesquiterpenoids from C. xanthorrhiza and C. zedoaria might be lead candidates for further developing COX-2 or iNOS inhibitors possessing cancer chemopreventive or anti-inflammatory properties.
authors.affiliation: College of Pharmacy, Ewha Womans University, Seoul, Korea. sklee@mm.ewha.ac.kr
authors.forename: Sang Kook
authors.initials: SK
authors.lastname: Lee
authors.forename: Chai-Hee
authors.initials: CH
authors.lastname: Hong
authors.forename: Sun-Kyung
authors.initials: SK
authors.lastname: Huh
authors.forename: Sun-Sook
authors.initials: SS
authors.lastname: Kim
authors.forename: O-Jin
authors.initials: OJ
authors.lastname: Oh
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Min
authors.forename: Kwang-Kyun
authors.initials: KK
authors.lastname: Park
authors.forename: Won-Yoon
authors.initials: WY
authors.lastname: Chung
authors.forename: Jae-Kwan
authors.initials: JK
authors.lastname: Hwang
mesh_terms: D000818:Animals; D018890:Chemoprevention; D051546:Cyclooxygenase 2; D007249:Inflammation; D007527:Isoenzymes / Q000096:biosynthesis* / Q000494:pharmacology; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000494:pharmacology; D012717:Sesquiterpenes / Q000494:pharmacology*; D030521:Zingiberaceae / Q000737:chemistry
chemical_list: D007527:Isoenzymes; D010936:Plant Extracts; D012717:Sesquiterpenes; D019001:Nitric Oxide Synthase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases