Abstract
Microglia in the central nervous system (CNS) play an important role in the initiation of neuroinflammatory response. Icariin, a compound from Epimedium brevicornum Maxim, has been reported to have anti-inflammatory effect on the macrophage cell line RAW264.7. However, it is currently unknown what anti-inflammatory role icariin may play in the CNS. Here, we reported the discovery that icariin significantly inhibited the release of nitric oxide (NO), prostaglandin E (PGE)-2, reactive oxygen species (ROS) and mRNA expression of proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 in lipopolysaccharide (LPS)-activated microglia. Icariin also inhibited the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 in a dose-dependent manner. Further mechanism studies revealed that icariin blocked TAK1/IKK/NF-kappaB and JNK/p38 MAPK pathways. It was also found that icariin reduced the degeneration of cortical neurons induced by LPS-activated microglia in neuron-microglia co-culture system. Taken together these findings provide mechanistic insights into the suppressive effect of icariin on LPS-induced neuroinflammatory response in microglia, and emphasize the neuroprotective effect and therapeutic potential of icariin in neuroinflammatory diseases.
Copyright 2010 Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Death / drug effects
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Cerebral Cortex / drug effects
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Cerebral Cortex / pathology
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Cyclooxygenase 2 / analysis
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Cytokines / analysis
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Cytokines / metabolism
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Dinoprostone / analysis
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Dinoprostone / metabolism
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Encephalitis / drug therapy
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Flavonoids / pharmacology*
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I-kappa B Kinase / antagonists & inhibitors*
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I-kappa B Kinase / metabolism
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JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors*
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JNK Mitogen-Activated Protein Kinases / metabolism
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Lipopolysaccharides
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MAP Kinase Kinase Kinases / antagonists & inhibitors*
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MAP Kinase Kinase Kinases / metabolism
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Microglia / drug effects*
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Microglia / enzymology
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NF-kappa B / antagonists & inhibitors*
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NF-kappa B / metabolism
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Neurons / drug effects*
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Neurons / enzymology
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Neuroprotective Agents / pharmacology*
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Nitric Oxide / analysis
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Nitric Oxide / metabolism
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Nitric Oxide Synthase Type II / analysis
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Phosphorylation
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Rats
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Rats, Sprague-Dawley
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Reactive Oxygen Species / analysis
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Reactive Oxygen Species / metabolism
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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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Cytokines
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Flavonoids
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Lipopolysaccharides
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NF-kappa B
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Neuroprotective Agents
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Reactive Oxygen Species
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Nitric Oxide
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Nitric Oxide Synthase Type II
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Cyclooxygenase 2
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I-kappa B Kinase
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JNK Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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MAP Kinase Kinase Kinases
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MAP kinase kinase kinase 7
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Dinoprostone
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icariin