Abstract
The present study was designed to investigate the effects of p-cymene on lipopolysaccharide (LPS)-induced inflammatory cytokine production both in vitro and in vivo. The production of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-10 (IL-10) in LPS-stimulated RAW 264.7 cells and C57BL/6 mice was evaluated by sandwich ELISA. Meanwhile, the mRNA levels of cytokine genes were examined in vitro by semiquantitative RT-PCR. In a further study, we analyzed the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways by western blotting. We found that p-cymene significantly regulated TNF-α, IL-1β, and IL-6 production in LPS-stimulated RAW 264.7 cells. Furthermore, the levels of relative mRNAs were also found to be downregulated. In in vivo trail, p-cymene markedly suppressed the production of TNF-α and IL-1β and increased IL-10 secretion. We also found that p-cymene inhibited LPS-induced activation of extracellular signal receptor-activated kinase 1/2, p38, c-Jun N-terminal kinase, and IκBα. These results suggest that p-cymene may have a potential anti-inflammatory action on cytokine production by blocking NF-κB and MAPK signaling pathways.
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-Inflammatory Agents, Non-Steroidal / metabolism
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology
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Cell Line
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Cymenes
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Enzyme Activation / drug effects*
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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 / drug therapy*
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Inflammation / immunology
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Inflammation / metabolism
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Interleukin-10 / biosynthesis
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Interleukin-10 / genetics
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Interleukin-1beta / biosynthesis
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Interleukin-1beta / genetics
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Interleukin-6 / biosynthesis
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Interleukin-6 / genetics
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JNK Mitogen-Activated Protein Kinases / metabolism
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Lipopolysaccharides
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MAP Kinase Signaling System
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Macrophages
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Mice
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Mice, Inbred C57BL
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Mitogen-Activated Protein Kinases / antagonists & inhibitors*
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Monoterpenes / metabolism
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Monoterpenes / pharmacology*
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NF-KappaB Inhibitor alpha
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NF-kappa B / antagonists & inhibitors*
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RNA, Messenger / biosynthesis
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Tumor Necrosis Factor-alpha / biosynthesis
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Tumor Necrosis Factor-alpha / genetics
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Cymenes
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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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Monoterpenes
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NF-kappa B
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Nfkbia protein, mouse
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RNA, Messenger
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Tumor Necrosis Factor-alpha
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Interleukin-10
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NF-KappaB Inhibitor alpha
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4-cymene
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Extracellular Signal-Regulated MAP Kinases
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases