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Journal Article
Research Support, Non-U.S. Gov't
Effect of 5-O-Methylhirsutanonol on nuclear factor-kappaB-dependent production of NO and expression of iNOS in lipopolysaccharide-induced RAW264.7 cells.
Journal of Agricultural and Food Chemistry 2008 January 10
Diarylheptanoids are known to have anti-inflammatory and anti-atherosclerotic activities in various cell types, including macrophages. 5- O-Methylhirsutanonol (5-MH) isolated from the leaves of Alnus japonica Steud exhibited the antioxidant activities on Cu (2+)- and AAPH-mediated low-density lipoprotein (LDL) oxidation in the thiobarbituric acid-reactive substances (TBARS) assay as well as the macrophage-mediated LDL oxidation. In the main study, we examined anti-inflammatory activities of 5- O-methylhirsutanonol (5-MH) on nuclear factor kappaB (NF-kappaB)-dependent nitric oxide (NO) production and expression of inducible nitric oxide synthease (iNOS) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. 5-MH inhibited NO production with an IC 50 value of 14.5 microM and expression of both iNOS protein and iNOS mRNA in a parallel dose-response manner. Then, expression of inflammation-associated genes, such as TNF-alpha, COX-2, and IL-1beta, was suppressed by 5-MH, as determined by reverse transcriptase polymerase chain reaction analysis. Moreover, 5-MH attenuated NF-kappaB activation by inhibition of hyperphosphorylation of IkappaB-alpha and its subsequent proteolytic degradation and p65 nuclear translocation, as well as preventing DNA-binding ability. In addition, 5-MH suppressed the mRNA expression of the gene reactive oxygen species (ROS) concerned in the regulation of NF-kappaB signaling.
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