Abstract
Compelling evidence supports the notion that the majority of neurodegenerative diseases are associated with microglia-mediated neuroinflammation. Therefore, quelling of microglial activation may lead to neuronal cell survival. The present study investigated the effects of Kamebakaurin (KMBK), a kaurane diterpene isolated from Isodon japonicus HARA (Labiatae), on the production of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated cytotoxicity in rat primary microglial cultures and the BV-2 cell line. KMBK significantly inhibited the LPS-induced production of nitric oxide (NO) in a concentration-dependent fashion in activated microglial cells. The mRNA and protein levels of inducible nitric oxide synthase (iNOS) and cyclooxycenase-2 (COX-2) were also decreased dose-dependently. Furthermore KMBK inhibited the JNK and p38 mitogen-activated protein kinases (MAPKs) in LPS-stimulated BV-2 microglial cells. Considering the results obtained, the present study authenticated the potential benefits of KMBK as a therapeutic target in ameliorating microglia-mediated neuroinflammatory diseases.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Cell Line, Transformed
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Cells, Cultured
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Cerebral Cortex / cytology
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Cerebral Cortex / drug effects
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Cerebral Cortex / metabolism
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Diterpenes / pharmacology*
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Enzyme Activation / drug effects
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Isodon / chemistry*
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JNK Mitogen-Activated Protein Kinases / metabolism*
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Lipopolysaccharides / toxicity
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Mice
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Microglia / drug effects*
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Microglia / immunology
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Microglia / metabolism*
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Microglia / pathology
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Neuritis / drug therapy
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Neuritis / immunology
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Neuritis / metabolism
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Phosphorylation / drug effects
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Protein Kinase Inhibitors / pharmacology
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Protein Processing, Post-Translational / drug effects
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Rats
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Rats, Sprague-Dawley
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Signal Transduction / drug effects
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Substantia Nigra / cytology
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Substantia Nigra / drug effects
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Substantia Nigra / metabolism
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p38 Mitogen-Activated Protein Kinases / metabolism*
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Diterpenes
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Lipopolysaccharides
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Protein Kinase Inhibitors
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kamebakaurin
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JNK Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases