Abstract
3-deoxysilybin (3-DS), also known as (-)-isosilandrin A, is a natural flavonoid of Silybum marianum. This study was designed to investigate the anti-inflammatory effect and the underlying molecular mechanisms of 3-DS in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. 3-DS dose-dependently inhibited the production of NO and the expression of iNOS in LPS-stimulated RAW264.7 macrophages. 3-DS also inhibited the production of pro-inflammatory cytokines (MCP-1, TNF-α, IL-6, and IL-1β) in LPS-stimulated RAW264.7 macrophages. Moreover, 3-DS decreased the NF-κB DNA binding activity in LPS-stimulated RAW264.7 macrophages. Furthermore, 3-DS suppressed NF-κB activation by inhibiting the degradation of IκBα and nuclear translocation of p65 subunit of NF-κB in LPS-stimulated RAW264.7 macrophages. Taken together, the present study suggests for the first time that 3-DS may exhibit an anti-inflammatory effect through the suppression of NF-κB transcriptional activation in LPS-stimulated RAW264.7 macrophages.
Keywords:
3-deoxysilybin; NF-κB; NO; iNOS; inflammation.
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 / isolation & purification
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Cell Line, Transformed
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Chemokine CCL2 / genetics
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Chemokine CCL2 / metabolism
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Dioxanes / isolation & purification
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Dioxanes / pharmacology*
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Flavanones / isolation & purification
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Flavanones / pharmacology*
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Flavonoids / isolation & purification
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Flavonoids / pharmacology*
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Gene Expression Regulation
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I-kappa B Proteins / genetics
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I-kappa B Proteins / metabolism
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Interleukin-1beta / genetics
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Interleukin-1beta / metabolism
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Interleukin-6 / genetics
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Interleukin-6 / metabolism
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Lipopolysaccharides / pharmacology*
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Macrophages / cytology
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Macrophages / drug effects*
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Macrophages / metabolism
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Mice
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NF-KappaB Inhibitor alpha
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NF-kappa B / genetics
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NF-kappa B / metabolism
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Nitric Oxide / metabolism
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Nitric Oxide Synthase Type II / genetics
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Nitric Oxide Synthase Type II / metabolism
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Plant Extracts / chemistry
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Signal Transduction
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Silybum marianum / chemistry*
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
Substances
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3-deoxysilybin
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Anti-Inflammatory Agents, Non-Steroidal
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Ccl2 protein, mouse
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Chemokine CCL2
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Dioxanes
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Flavanones
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Flavonoids
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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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NF-kappa B
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Nfkbia protein, mouse
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Plant Extracts
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Tumor Necrosis Factor-alpha
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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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Nos2 protein, mouse