Comparative studies on the suppression of nitric oxide synthase by curcumin and its hydrogenated metabolites through down-regulation of IκB kinase and NFκB activation in macrophages
Section snippets
Reagents
LPS (Escherichia coli 0127: E8), sufanilamide, naphthylethylenediamine dihydrochloride, and DTT were purchased from the Sigma Chemical Co. Acrylamide was purchased from the E. Merck Co. Synthetic curcumin was provided by the Yung Shin Pharmaceutical Ind. Co. Tetrahydrocurcumin, hexahydrocurcumin, and octahydrocurcumin (Fig. 1 ) were prepared by hydrogenation of curcumin with PtO2 as described in our previous report [30].
Preparation of curcumin derivatives
Curcumin was converted to tetrahydrocurcumin (4H), hexahydrocurcumin (6H),
Effects of various curcuminoids on iNOS protein
Curcumin, tetrahydrocurcumin, hexahydrocurcumin, and octahydrocurcumin were examined to determine whether they affect iNOS protein and NO production in macrophages activated with LPS for 6–18 hr. Inhibition of iNOS protein by these compounds was detected at 10 μM. The inhibitory activity of tetrahydrocurcumin, hexahydrocurcumin, and octahydrocurcumin was less than that of curcumin (Fig. 2 A). The inhibition of NO generation in the LPS-activated macrophages with curcumin, tetrahydrocurcumin
Discussion
Curcumin, a naturally occurring anti-inflammatory agent and antioxidant, has been shown to inhibit tumors in several organs, including 7,12-dimethylbenz[a]anthracene-induced and 12-O-tetradecanoylphorbol-13-acetate-promoted skin tumors [2], benzo[a]pyrene-induced forestomach tumors [41], and azoxymethane-induced intestinal tumors in mice [1]. Chan et al.[6] have shown that, in vivo, oral treatments of 0.5 mL of a 10 μM solution of curcumin (92 ng/g of body weight) reduced iNOS mRNA expression
Acknowledgements
This study was supported by the National Science Council (NSC 89-EPA-Z-002–004 and NSC 89–2316-B-002–016) and by the National Health Research Institute (DOH 88-HR-403).
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