Abstract
A quaternary benzo [c] alkaloid chelerythrine (CHE), which is a traditional herbal prescription, has been used for the treatment of various inflammatory diseases. To gain insight into the anti-inflammatory effect and molecular mechanisms underlying the anti-inflammatory activity of CHE, we used experimentally induced mice endotoxic shock moled and lipopolysaccharide (LPS)-induced murine peritoneal macrophages to examine the anti-inflammatory function of CHE. CHE displayed significant anti-inflammatory effects in experimentally induced mice endotoxic shock model in vivo through inhibition of LPS-induced tumor necrosis factor-alpha (TNF-α) level and nitric oxide (NO) production in serum. Additionally, our data suggest that CHE treatment inhibits LPS-induced TNF-α level and NO production in LPS-induced murine peritoneal macrophages through selective inhibition of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) activation. Moreover, the effects of CHE on NO and cytokine TNF-α production can possibly be explained by the role of p38 MAPK and ERK1/2 in the regulation of inflammatory mediators expression.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Bacterial Agents / pharmacology
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Anti-Bacterial Agents / therapeutic use
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Anti-Inflammatory Agents / pharmacology
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Anti-Inflammatory Agents / therapeutic use
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Benzophenanthridines / pharmacology*
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Benzophenanthridines / therapeutic use
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Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Female
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Inflammation / drug therapy*
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Inflammation Mediators / metabolism
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Lipopolysaccharides
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MAP Kinase Signaling System / drug effects*
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Macrophages, Peritoneal / drug effects*
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Macrophages, Peritoneal / immunology
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Macrophages, Peritoneal / metabolism
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Male
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Mice
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Nitric Oxide / blood
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Shock, Septic / drug therapy*
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Shock, Septic / immunology
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Shock, Septic / metabolism
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Tumor Necrosis Factor-alpha / blood
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Anti-Bacterial Agents
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Anti-Inflammatory Agents
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Benzophenanthridines
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Inflammation Mediators
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Lipopolysaccharides
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Tumor Necrosis Factor-alpha
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Nitric Oxide
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chelerythrine
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Extracellular Signal-Regulated MAP Kinases
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p38 Mitogen-Activated Protein Kinases