Abstract
Angelica sinensis (AS), an herb used in traditional Chinese medicine, is thought to have anti-inflammatory activities. Ligustilide is its most abundant ingredient. This study sought to determine ligustilide's effects on lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages. Ligustilide significantly suppressed the production of nitric oxide (NO), prostaglandin E(2) (PGE(2)) and tumor necrosis factor-α (TNF-α). The inhibition of NO was concomitant with a decrease in the protein and mRNA levels of LPS-induced nitric oxide synthase (iNOS). Furthermore, activation of activator protein-1 (AP-1) and nuclear factor κB (NF-κB) in the nucleus and the cytosolic degradation of IκBα were abrogated by ligustilide. Ligustilide also inhibited the phosphorylation of IκB kinase (IKK) and mitogen-activated protein kinases (MAPKs), including p38 MAPK, extracellular signal-regulated kinase (ERK1/2) and c-Jun N-terminal kinase (JNK). The intracellular reactive oxygen species (iROS) level was also significantly decreased. These results suggest that ligustilide exhibits anti-inflammatory activities by blocking the activation of MAPKs/IKK and the downstream transcription factors AP-1 and NF-κB, which may result from ligustilide's down-regulation of iROS production.
Copyright © 2011 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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4-Butyrolactone / analogs & derivatives*
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4-Butyrolactone / pharmacology
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Animals
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Cell Line
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Dinoprostone / antagonists & inhibitors
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Dinoprostone / biosynthesis
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Down-Regulation / drug effects
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I-kappa B Kinase / antagonists & inhibitors
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I-kappa B Kinase / genetics
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I-kappa B Kinase / metabolism
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Lipopolysaccharides / pharmacology
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MAP Kinase Kinase 4 / antagonists & inhibitors
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MAP Kinase Signaling System / drug effects
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Macrophages / drug effects
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Macrophages / enzymology
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Macrophages / metabolism
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Mice
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Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors*
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Mitogen-Activated Protein Kinase Kinases / metabolism
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Nitric Oxide / antagonists & inhibitors
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Nitric Oxide / biosynthesis
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Nitric Oxide Synthase Type II / antagonists & inhibitors*
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Nitric Oxide Synthase Type II / biosynthesis
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Nitric Oxide Synthase Type II / genetics
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Phosphorylation / drug effects
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Reactive Oxygen Species / antagonists & inhibitors*
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Reactive Oxygen Species / metabolism
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Signal Transduction / drug effects*
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Transcription Factor AP-1 / antagonists & inhibitors*
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Transcription Factor AP-1 / genetics
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Transcription Factor AP-1 / metabolism
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Transcription Factor RelA / antagonists & inhibitors*
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Transcription Factor RelA / genetics
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Transcription Factor RelA / metabolism
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / biosynthesis
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
Substances
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Lipopolysaccharides
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Reactive Oxygen Species
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Transcription Factor AP-1
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Transcription Factor RelA
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Tumor Necrosis Factor-alpha
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Nitric Oxide
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ligustilide
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Nitric Oxide Synthase Type II
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Nos2 protein, mouse
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I-kappa B Kinase
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p38 Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 4
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Mitogen-Activated Protein Kinase Kinases
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Dinoprostone
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4-Butyrolactone