Abstract
Thymol is a natural monoterpene phenol primarily found in thyme, oregano, and tangerine peel. It has been shown to possess anti-inflammatory property both in vivo and in vitro. In the present paper, we studied the anti-inflammatory effect of thymol in lipopolysaccharide (LPS)-stimulated mouse mammary epithelial cells (mMECs). The mMECs were stimulated with LPS in the presence or absence of thymol (10, 20, 40 μg/mL). The concentrations of tumor necrosis factor α (TNF-α), interleukin (IL)-6, and IL-1β in the supernatants of culture were determined using enzyme-linked immunosorbent assay. Cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), nuclear factor-κB (NF-κB), and inhibitor protein of NF-κB (IκBα) were measured using western blot. The results showed that thymol markedly inhibited the production of TNF-α and IL-6 in LPS-stimulated mMECs. The expression of iNOS and COX-2 was also suppressed by thymol in a dose-dependent manner. Furthermore, thymol blocked the phosphorylation of IκBα, NF-κB p65, ERK, JNK, and p38 mitogen-activated protein kinases (MAPKs) in LPS-stimulated mMECs. These results indicate that thymol exerted anti-inflammatory property in LPS-stimulated mMECs by interfering the activation of NF-κB and MAPK signaling pathways. Thereby, thymol may be a potential therapeutic agent against mastitis.
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-Infective Agents / pharmacology
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Anti-Inflammatory Agents / pharmacology*
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Cell Survival / drug effects
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Cells, Cultured
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Cyclooxygenase 2 / analysis
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Down-Regulation
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Epithelial Cells / immunology
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Female
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I-kappa B Proteins / metabolism
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Inflammation / chemically induced
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Inflammation / drug therapy*
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Inflammation / immunology
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Interleukin-1beta / analysis
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Interleukin-6 / analysis
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Interleukin-6 / biosynthesis
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JNK Mitogen-Activated Protein Kinases / metabolism
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Lipopolysaccharides
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MAP Kinase Signaling System / drug effects*
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Macrophages / metabolism
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Mammary Glands, Animal / cytology
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Mammary Glands, Animal / immunology
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Mastitis / drug therapy
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Mice
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Mice, Inbred BALB C
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NF-KappaB Inhibitor alpha
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Nitric Oxide Synthase Type II
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Phosphorylation
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Thymol / pharmacology*
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Transcription Factor RelA / biosynthesis
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Transcription Factor RelA / metabolism*
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Tumor Necrosis Factor-alpha / analysis
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Tumor Necrosis Factor-alpha / biosynthesis
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Anti-Infective Agents
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Anti-Inflammatory Agents
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I-kappa B Proteins
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Interleukin-1beta
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Interleukin-6
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Lipopolysaccharides
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Nfkbia protein, mouse
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Transcription Factor RelA
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Tumor Necrosis Factor-alpha
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interleukin-6, mouse
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NF-KappaB Inhibitor alpha
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Thymol
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Nitric Oxide Synthase Type II
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Cyclooxygenase 2
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Extracellular Signal-Regulated MAP Kinases
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JNK Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases