Abstract
The overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) is known to be responsible for vasodilation and hypotension observed in septic shock and inflammation. Inhibitors of iNOS, thus, may be useful candidates for the treatment of inflammatory diseases accompanied by overproduction of NO. In the course of screening oriental anti-inflammatory herbs for the inhibitory activity of NO synthesis, a crude methanolic extract ofCurcuma zedoaria exhibited significant activity. The activity-guided fractionation and repetitive chromatographic procedures with the EtOAc soluble fraction allowed us to isolate three active compounds. They were identified as 1,7-bis (4-hydroxyphenyl)-1,4,6-heptatrien-3-one (1), procurcumenol (2) and epiprocurcumenol (3) by spectral data analyses. Their concentrations for the 50% inhibition of NO production (IC50) in lipopolysaccharide (LPS)-activated macrophages were 8, 75, 77 μM, respectively. Compound1 showed the most potent inhibitory activity for NO production in LPS-activated macrophages, while the epimeric isomers, compound2 and3 snowed weak and similar potency. Inhibition of NO synthesis by compound1 was very weak when activated macrophages were treated with1 after iNOS induction. In the immunoblot analysis, compound1 suppressed the expression of iNOS in a dose-dependent manner. In summary, 1,7-bis (4-hydroxyphenyl)-1,4,6-heptatrien-3-one fromCurcuma zedoaria inhibited NO production in LPS-activated macrophages through suppression of iNOS expression. These results imply that the traditional use ofC. zedoaria rhizome as anti-inflammatory drug may be explained at least in part, by inhibition of NO production.
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Jang, M.K., Lee, H.J., Kim, J.S. et al. A curcuminoid and two sesquiterpenoids fromCurcuma zedoaria as Inhibitors of nitric oxide synthesis in activated macrophages. Arch Pharm Res 27, 1220–1225 (2004). https://doi.org/10.1007/BF02975885
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DOI: https://doi.org/10.1007/BF02975885