Abstract
The inhibitory effect of 15-methoxypinusolidic acid (15-MPA) isolated from Biota orientalis (Cupressaceae) on lipopolysaccharide (LPS)-induced inflammation in microglial BV2 cells was investigated. 15-MPA significantly reduced the expression of inducible nitric oxide synthase (iNOS), the activity of iNOS, and the production of nitric oxide (NO) in LPS-stimulated BV2 cells. In addition, 15-MPA significantly suppressed the expressions of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and cyclooxygenase (COX)-2. However, 15-MPA did not affect LPS-induced degradation of inhibitor kappaB-alpha (IkappaB-alpha) and translocation of nuclear factor-kappaB (NF-kappaB) into the nucleus. LPS-activated p38 MAPK, extracellular signal-regulated kinase (ERK)-1/2, and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) were not affected by 15-MPA. Taken together, this study demonstrates that 15-MPA inhibits LPS-induced iNOS expression and NO production, independent on MAPK and NF-kappaB, suggesting a potential anti-inflammatory effect of the compound on microglial cells.
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 / pharmacology*
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Cell Line
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Cell Nucleus / metabolism
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Cyclooxygenase 2 / metabolism
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Diterpenes / pharmacology*
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I-kappa B Proteins / metabolism
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Lipopolysaccharides / immunology
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MAP Kinase Kinase 4 / metabolism
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Mice
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Microglia / drug effects*
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Microglia / enzymology
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Microglia / immunology
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Microglia / metabolism
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Mitogen-Activated Protein Kinase 3 / metabolism
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NF-KappaB Inhibitor alpha
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NF-kappa B / metabolism
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Nitric Oxide / metabolism*
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Nitric Oxide Synthase Type II / metabolism*
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Thuja
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p38 Mitogen-Activated Protein Kinases / drug effects
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p38 Mitogen-Activated Protein Kinases / immunology
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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15-methoxypinusolidic acid
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Anti-Inflammatory Agents, Non-Steroidal
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Diterpenes
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I-kappa B Proteins
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Lipopolysaccharides
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NF-kappa B
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Nfkbia protein, mouse
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NF-KappaB Inhibitor alpha
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Nitric Oxide
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Nitric Oxide Synthase Type II
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Ptgs2 protein, mouse
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Cyclooxygenase 2
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Mitogen-Activated Protein Kinase 3
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p38 Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 4