کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2525499 | 1119616 | 2008 | 7 صفحه PDF | دانلود رایگان |
Curcumin, at high concentrations (>2 μM), inhibits the production of nitric oxide (NO) and the expression of inducible NO synthase (iNOS) through inactivation of nuclear factor (NF)-κB and, at low concentrations, induces the expression of heme oxygenase (HO)-1 in macrophages. Here, we demonstrated that curcumin at low concentrations (0.5–2 μM) can also inhibit NO production and iNOS expression in lipopolysaccharide (LPS)-activated RAW264.7 macrophages only when the cells were pretreated for at least 6 h with curcumin. Curcumin induced dose- and time-dependent HO-1 expression, and this was coincident with the inhibitory effects of low concentrations of curcumin on NO production and iNOS expression. Blockage of HO-1 activity or knockdown of HO-1 expression abolished the inhibitory effects of curcumin. Over-expression of HO-1 or exogenous addition of carbon monoxide, a byproduct derived from heme degradation, mimicked the inhibitory action of low concentrations of curcumin. Moreover, LPS-induced NF-κB was diminished in macrophages subjected to prolonged treatment with low concentrations of curcumin. Treatment with HO inhibitor abolished the inhibitory effect of curcumin on LPS-induced NF-κB activation. Collectively, we provide evidence to support the important role of HO-1 in inhibition of NO production and iNOS expression by curcumin even at low concentrations.
Journal: Biomedicine & Pharmacotherapy - Volume 62, Issue 9, November 2008, Pages 630–636