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Effect of 5-O-Methylhirsutanonol on Nuclear Factor-κB-Dependent Production of NO and Expression of iNOS in Lipopolysaccharide-Induced RAW264.7 Cells

Author:
Han, J.M., Lee, W.S., Kim, J.R., Son, J., Kwon, O.H., Lee, H.J., Lee, J.J., Jeona, T.S.
Source:
Journal of agricultural and food chemistry 2008 v.56 no.1 pp. 92-98
ISSN:
0021-8561
Subject:
Alnus japonica, leaves, aromatic compounds, antioxidants, antioxidant activity, low density lipoprotein, macrophages, gene expression, transcription factors, transcription (genetics), inflammation, messenger RNA, nitrous oxide, nitric oxide synthase, nitric oxide, reactive oxygen species, medicinal plants, medicinal properties
Abstract:
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 Cu2+- 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 κB (NF-κB)-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 IC50 value of 14.5 μM and expression of both iNOS protein and iNOS mRNA in a parallel dose-response manner. Then, expression of inflammation-associated genes, such as TNF-α, COX-2, and IL-1β, was suppressed by 5-MH, as determined by reverse transcriptase polymerase chain reaction analysis. Moreover, 5-MH attenuated NF-κB activation by inhibition of hyperphosphorylation of IκB-α 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-κB signaling.
Agid:
722581