Suppressive effect of natural sesquiterpenoids on inducible cyclooxygenase (COX-2) and nitric oxide synthase (iNOS) activity in mouse macrophage cells.
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.
Lee
Sang Kook
SK
College of Pharmacy, Ewha Womans University, Seoul, Korea. sklee@mm.ewha.ac.kr
Hong
Chai-Hee
CH
Huh
Sun-Kyung
SK
Kim
Sun-Sook
SS
Oh
O-Jin
OJ
Min
Hye-Young
HY
Park
Kwang-Kyun
KK
Chung
Won-Yoon
WY
Hwang
Jae-Kwan
JK
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
D007527:Isoenzymes; D010936:Plant Extracts; D012717:Sesquiterpenes; D019001:Nitric Oxide Synthase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases