title: 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.affiliation: †Department of Pharmacology, College of Oriental Medicine, Sangji University, Gangwon-do 220-702, Republic of Korea.
authors.forename: Se-Yun
authors.initials: SY
authors.lastname: Cheon
authors.affiliation: †Department of Pharmacology, College of Oriental Medicine, Sangji University, Gangwon-do 220-702, Republic of Korea.
authors.forename: Kyung-Sook
authors.initials: KS
authors.lastname: Chung
authors.affiliation: †Department of Pharmacology, College of Oriental Medicine, Sangji University, Gangwon-do 220-702, Republic of Korea.
authors.forename: Eunjin
authors.initials: E
authors.lastname: Jeon
authors.affiliation: ‡Department of Agroindustrial Technology, Lambung Mangkurat University, Banjarbaru, Indonesia.
authors.forename: Agung
authors.initials: A
authors.lastname: Nugroho
authors.affiliation: §Department of Pharmaceutical Engineering, College of Health Science, Sangji University, Wonju, Republic of Korea.
authors.forename: Hee-Jun
authors.initials: HJ
authors.lastname: Park
authors.affiliation: †Department of Pharmacology, College of Oriental Medicine, Sangji University, Gangwon-do 220-702, Republic of Korea.
authors.forename: Hyo-Jin
authors.initials: HJ
authors.lastname: An
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D020170:Caspase 1 / Q000187:drug effects* / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000037:antagonists & inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D005419:Flavonoids; D020672:I-kappa B Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; C468886:saxifragin; D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D020170:Caspase 1; D015232:Dinoprostone