Abstract
Nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) are the major mediators produced in activated macrophages which contribute to the circulatory failure associated with septic shock. An activity-guided fractionation of an MeOH extract of stem bark of Magnolia obovata afforded two inhibitors of NO production in lipopolysaccharides (LPS)-activated macrophages by the suppression of i-NOS expression. Their structures were elucidated by spectroscopic methods to be magnolol and honokiol with IC50 values of 16.8 and 6.4 microM, respectively. They also inhibited the production of TNF-alpha in LPS-activated macrophages. Thus, these compounds may be possible candidates for the development of new drugs to treat endotoxemia accompanied by the overproduction of NO and TNF-alpha.
Publication types
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Letter
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Biphenyl Compounds / chemistry
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Biphenyl Compounds / pharmacology*
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Blotting, Western
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Cell Line
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Lignans*
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Lipopolysaccharides
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Macrophage Activation
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Macrophages / drug effects*
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Magnetic Resonance Spectroscopy
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Magnoliopsida / chemistry*
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Mice
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Nitric Oxide / antagonists & inhibitors
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Nitric Oxide / biosynthesis*
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Nitric Oxide Synthase / antagonists & inhibitors*
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / biosynthesis*
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Biphenyl Compounds
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Enzyme Inhibitors
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Lignans
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Lipopolysaccharides
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Tumor Necrosis Factor-alpha
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magnolol
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honokiol
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Nitric Oxide
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Nitric Oxide Synthase