Anti-rheumatoid arthritis effects of flavonoids from Daphne genkwa |
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Affiliation: | 1. School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, China;2. Tang Center of Herbal Medicine Research and Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL 60637, United States |
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Abstract: | ObjectiveThis study aims to select the most effective anti-Rheumatoid Arthritis (RA) component of flavonoids from Daphne genkwa Sieb. et Zucc. by anti-inflammatory and immunomodulatory effects in vitro, and to elucidate the mechanism.MethodsThe anti-inflammatory and immunomodulatory effects of total flavonoids (TF) and four flavonoid components (genkwanin, hydroxygenkwanin, luteolin and apigenin) were determined by pharmacological approach in LPS-induced RAW 264.7 macrophages and ConA-induced T lymphocytes. Principal component analysis (PCA) was used to obtain the optimal anti-RA component in vitro. Western blot and real-time quantitative PCR (q-PCR) were used to explore the mechanisms. Finally, the in vitro anti-RA effect was verified by human rheumatoid arthritis fibroblast-like synoviocytes (FLSs).ResultsTF and four flavonoids significantly reduced the expressions of NO, iNOS, TNF-α, IL-6, IFN-γ and IL-2. PCA showed that genkwanin was the most effective anti-RA component in vitro. Genkwanin inhibited nuclear factor-κB (NF-κB) pathway by decreasing the phosphorylation levels of IKK, IκB and NF-κB, and down-regulated the expressions of iNOS, COX-2 and IL-6 mRNA. Genkwanin also inhibited the abnormal proliferation of FLSs and down-regulated the secretions of NO and IL-6.ConclusionThe most effective anti-RA component was genkwanin. Genkwanin exerts anti-RA effect through down-regulating the activation of NF-κB pathway and mRNA expressions of inflammatory mediators, and also by inhibiting the abnormal proliferation of FLSs and its NO and IL-6 secretion levels. |
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Keywords: | Flavonoids Genkwanin Rheumatoid arthritis RA" },{" #name" :" keyword" ," $" :{" id" :" k0030" }," $$" :[{" #name" :" text" ," _" :" Rheumatoid arthritis LPS" },{" #name" :" keyword" ," $" :{" id" :" k0040" }," $$" :[{" #name" :" text" ," _" :" Lipopolysaccharide IL-6" },{" #name" :" keyword" ," $" :{" id" :" k0050" }," $$" :[{" #name" :" text" ," _" :" Interleukin-6 TNF-α" },{" #name" :" keyword" ," $" :{" id" :" k0060" }," $$" :[{" #name" :" text" ," _" :" Tumor necrosis factor-alpha NO" },{" #name" :" keyword" ," $" :{" id" :" k0070" }," $$" :[{" #name" :" text" ," _" :" Nitric oxide iNOS" },{" #name" :" keyword" ," $" :{" id" :" k0080" }," $$" :[{" #name" :" text" ," _" :" Inducible nitric oxide synthase G" },{" #name" :" keyword" ," $" :{" id" :" k0090" }," $$" :[{" #name" :" text" ," _" :" Genkwanin H" },{" #name" :" keyword" ," $" :{" id" :" k0100" }," $$" :[{" #name" :" text" ," _" :" Hydroxygenkwanin L" },{" #name" :" keyword" ," $" :{" id" :" k0110" }," $$" :[{" #name" :" text" ," _" :" Luteolin A" },{" #name" :" keyword" ," $" :{" id" :" k0120" }," $$" :[{" #name" :" text" ," _" :" Apigenin TF" },{" #name" :" keyword" ," $" :{" id" :" k0130" }," $$" :[{" #name" :" text" ," _" :" Total flavonoid ConA" },{" #name" :" keyword" ," $" :{" id" :" k0140" }," $$" :[{" #name" :" text" ," _" :" Concanavalin A IFN-γ" },{" #name" :" keyword" ," $" :{" id" :" k0150" }," $$" :[{" #name" :" text" ," _" :" Interferon-γ IL-2" },{" #name" :" keyword" ," $" :{" id" :" k0160" }," $$" :[{" #name" :" text" ," _" :" Interleukin-2 PCA" },{" #name" :" keyword" ," $" :{" id" :" k0170" }," $$" :[{" #name" :" text" ," _" :" Principal component analysis NF-κB" },{" #name" :" keyword" ," $" :{" id" :" k0180" }," $$" :[{" #name" :" text" ," _" :" Nuclear factor kappa B COX-2" },{" #name" :" keyword" ," $" :{" id" :" k0190" }," $$" :[{" #name" :" text" ," _" :" Cyclooxygenase-2 FLS" },{" #name" :" keyword" ," $" :{" id" :" k0200" }," $$" :[{" #name" :" text" ," _" :" Fibroblast-like synoviocyte ELISA" },{" #name" :" keyword" ," $" :{" id" :" k0210" }," $$" :[{" #name" :" text" ," _" :" Enzyme-linked immunosorbent assay DMEM" },{" #name" :" keyword" ," $" :{" id" :" k0220" }," $$" :[{" #name" :" text" ," _" :" Dulbecco’s modified Eagle’s medium FBS" },{" #name" :" keyword" ," $" :{" id" :" k0230" }," $$" :[{" #name" :" text" ," _" :" Fetal bovine serum MTT" },{" #name" :" keyword" ," $" :{" id" :" k0240" }," $$" :[{" #name" :" text" ," _" :" 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide |
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