Anti-inflammatory Activity of Saxifragin via Inhibition of NF-κB Involves Caspase-1 Activation.

Abstract

Saxifragin, the 5-glucoside of the flavonoid quercetin, is found in plants and insects. It has been reported that saxifragin has peroxynitrite-scavenging effects. However, the mechanism of anti-inflammatory effects of saxifragin has not yet been clearly identified. In this study, we investigated the anti-inflammatory effects of saxifragin in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and animal models of inflammation. We found that saxifragin suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-activated RAW 264.7 macrophages by suppressing the level of protein and mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively. Furthermore, saxifragin inhibited mRNA expression of pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β. We studied the inhibitory effects of saxifragin on the nuclear translocation of nuclear factor (NF)-κB, activation of caspase-1, and phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK). Furthermore, pretreatment with saxifragin increased the survival rate of mice with LPS-induced septic death. Collectively, these findings suggest that saxifragin exerts anti-inflammatory activity by inhibiting NF-κB, caspase-1, and mitogen-activated protein kinase (MAPK) activation.

• Authors: Se-Yun Cheon, Kyung-Sook Chung, Eunjin Jeon, Agung Nugroho, Hee-Jun Park, Hyo-Jin An
• Journal: Journal of natural products (J Nat Prod) Vol. 78 Issue 7 Pg. 1579-85 (Jul 24 2015) ISSN: 1520-6025 [Electronic] United States
• PMID: 26171782 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Flavonoids
• I-kappa B Proteins
• Interleukin-6
• Lipopolysaccharides
• NF-kappa B
• saxifragin
• Nitric Oxide
• NOS2 protein, human
• Nitric Oxide Synthase Type II
• Cyclooxygenase 2
• Extracellular Signal-Regulated MAP Kinases
• Mitogen-Activated Protein Kinases
• Caspase 1
• Dinoprostone

Topics

• Animals
• Anti-Inflammatory Agents (chemistry, pharmacology)
• Caspase 1 (drug effects, metabolism)
• Cyclooxygenase 2 (metabolism)
• Dinoprostone (antagonists & inhibitors)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Flavonoids (chemistry, pharmacology)
• I-kappa B Proteins (metabolism)
• Inflammation (drug therapy)
• Interleukin-6 (metabolism)
• Lipopolysaccharides (pharmacology)
• Macrophages (drug effects)
• Mice
• Mitogen-Activated Protein Kinases (metabolism)
• Molecular Structure
• NF-kappa B (antagonists & inhibitors)
• Nitric Oxide (biosynthesis)
• Nitric Oxide Synthase Type II (antagonists & inhibitors)
• Signal Transduction (drug effects)