Abstract
We investigated the anti-inflammatory effects of 3α-hydroxy-lup-20(29)-en-23, 28-dioic acid (HLEDA)-a lupane-type triterpene isolated from leaves of Acanthopanax gracilistylus W. W.Smith (AGS), as well as the underlying molecular mechanisms in lipopolysaccharide (LPS)-induced RAW264.7 cells. Our results demonstrated that HLEDA concentration-dependently reduced the production of nitric oxide (NO), significantly suppressed LPS-induced expression of TNF-α and IL-1β at the mRNA and protein levels in RAW264.7 cells. Further analysis revealed that HLEDA could reduce the secretion of High Mobility Group Box 1 (HMGB1). Additionally, the results showed that HLEDA efficiently decreased nuclear factor-kappaB (NF-κB) activation by inhibiting the degradation and phosphorylation of IκBα. These results suggest that HLEDA exerts anti-inflammatory properties in LPS-induced macrophages, possibly through inhibition of the NF-κB signaling pathway, which mediates the expression of pro-inflammatory cytokines. These results warrant further studies that would concern candidate therapy for diseases, such as fulminant hepatitis and rheumatology of triterpenoids in AGS.
Keywords:
3α-hydroxy-lup-20(29)-en-23,28-dioic acid; HMGB1; IL-1β; TNF-α; anti-inflammatory.
MeSH terms
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Animals
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Anti-Inflammatory Agents / isolation & purification
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Anti-Inflammatory Agents / pharmacology*
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Cell Line
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Dose-Response Relationship, Drug
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Drugs, Chinese Herbal / chemistry*
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Eleutherococcus
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Gene Expression
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HMGB1 Protein / antagonists & inhibitors*
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HMGB1 Protein / genetics
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HMGB1 Protein / metabolism
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Inflammation
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Interleukin-1beta / antagonists & inhibitors*
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Interleukin-1beta / genetics
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Interleukin-1beta / metabolism
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Lipopolysaccharides / antagonists & inhibitors
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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 / antagonists & inhibitors
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NF-KappaB Inhibitor alpha / genetics
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NF-KappaB Inhibitor alpha / metabolism
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Nitric Oxide / antagonists & inhibitors
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Nitric Oxide / biosynthesis
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Phosphorylation / drug effects
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Triterpenes / isolation & purification
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Triterpenes / pharmacology*
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Tumor Necrosis Factor-alpha / antagonists & inhibitors*
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Anti-Inflammatory Agents
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Drugs, Chinese Herbal
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HMGB1 Protein
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HMGB1 protein, mouse
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IL1B protein, mouse
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Interleukin-1beta
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Lipopolysaccharides
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Triterpenes
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Tumor Necrosis Factor-alpha
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3-hydroxylup-20(29)en-23,28-dioic acid
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NF-KappaB Inhibitor alpha
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Nitric Oxide
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Acanthopanax gracilistylus, extract