Flavonol-rich RVHxR from Rhus verniciflua Stokes and its major compound fisetin inhibits inflammation-related cytokines and angiogenic factor in rheumatoid arthritic fibroblast-like synovial cells and in vivo models

Autor: GeumSeon Jeon, Dong-Suk Park, Jeong-Eun Huh, Hyun-Su Woo, Ha-Ru Yang, Do-Young Choi, Jae-Dong Lee
Rok vydání: 2008
Předmět:
MAPK/ERK pathway
Vascular Endothelial Growth Factor A
Chemokine
Flavonols
Pyridines
medicine.medical_treatment
Interleukin-1beta
Angiogenesis Inhibitors
Arthritis
Rheumatoid
Rats
Sprague-Dawley
chemistry.chemical_compound
Mice
Cell Movement
Immunology and Allergy
Hypersensitivity
Delayed
Enzyme Inhibitors
biology
Neovascularization
Pathologic
Anti-Inflammatory Agents
Non-Steroidal
Synovial Membrane
Imidazoles
Vascular endothelial growth factor
Vascular endothelial growth factor A
Cytokine
Mice
Inbred DBA
Cytokines
medicine.symptom
Rhus
Immunology
Inflammation
Proinflammatory cytokine
medicine
Animals
Humans
Collagen Type II
Cell Proliferation
Pharmacology
Flavonoids
business.industry
Oxazolone
Fibroblasts
Rats
Disease Models
Animal
chemistry
Cancer research
biology.protein
business
Protein Kinases
Fisetin
Zdroj: International immunopharmacology. 9(3)
ISSN: 1878-1705
Popis: Rheumatoid arthritis (RA) is an aggressive inflammatory disease in which cytokines/chemokines are thought to recruit leukocytes and induce angiogenesis. The aim of this study is to investigate the effect of flavonol-rich residual layer of hexane fraction from Rhus verniciflua Stokes (RVHxR) and its major compound fisetin on inflammatory cytokine/chemokine production and angiogenic factor in IL-1beta-stimulated RA fibroblast-like synovial cells (FLS) and inflammatory in vivo models. Flavonol-rich RVHxR and its major compound fisetin significantly inhibited IL-1beta-induced FLS proliferation in a dose-dependent manner. Flavonol-rich RVHxR and fisetin significantly decreased IL-1beta-induced inflammatory cytokines (TNF-alpha, interleukin (IL)-6)/chemokines (IL-8, monocyte chemoattractant protein (MCP)-1), and vascular endothelial growth factor (VEGF) of RA FLS. Flavonol-rich RVHxR dose dependently diminished the phophorylation of extracellular signal regulated kinase (ERK) and phospho-Jun NH((2))-terminal kinase (JNK), and its down regulation induced by RVHxR at nontoxic concentrations, while activated the phosphorylation of p38 MAPK in IL-1beta-stimulated RA FLS. The p38 specific inhibitor SB203580 cotreatment with RVHxR effectively increased the expression of VEGF and blocked the phosphorylation of p38 MAPK in IL-1beta-stimulated RA FLS, confirming a critical role of p38 MAPK pathway in angiogenesis inhibition. In experimental inflammation-related models, flavonol-rich RVHxR and fisetin have shown significant anti-inflammatory activities on vascular permeability, leukocyte migration and cellular immunity. Also, flavonol-rich RVHxR and fisetin treatments significantly reduced the incidence and severity of collagen-induced arthritis model. These results suggest that RVHxR and its major compound fisetin have shown potent suppressive effects on some inflammatory cytokines/chemokines and angiogenic factor in IL-1beta-stimulated RA FLS and inflammatory in vivo models. We believe that flavonol-rich RVHxR is a potential therapeutic agent in the treatment of inflammatory and angiogenesis related diseases.
Databáze: OpenAIRE
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