Dioscorealide B suppresses LPS‐induced nitric oxide production and inflammatory cytokine expression in RAW 264.7 macrophages: The inhibition of NF‐κB and ERK1/2 activation |
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Authors: | Poonsit Hiransai Suvina Ratanachaiyavong Arunporn Itharat Potchanapond Graidist Prasit Ruengrairatanaroj Juntipa Purintrapiban |
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Institution: | 1. Faculty of Medicine, Department of Biomedical Sciences, Prince of Songkla University, Hat‐Yai, Songkhla 90110, Thailand;2. Faculty of Medicine, Applied Thai Traditional Medicine Center, Thammasat University, Klongluang, Pathumtani 12121, Thailand;3. Tumor Biology Research Unit, Faculty of Medicine, Prince of Songkla University, Hat‐Yai, Songkhla 90110, Thailand;4. Department of Pathology, Faculty of Medicine, Prince of Songkla University, Hat‐Yai, Songkhla 90110, Thailand |
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Abstract: | Dioscorealide B (DB), a naphthofuranoxepin has been purified from an ethanolic extract of the rhizome of Dioscorea membranacea Pierre ex Prain & Burkill which has been used to treat inflammation and cancer in Thai Traditional Medicine. Previously, DB has been reported to have anti‐inflammatory activities through reducing nitric oxide (NO) and tumor necrosis factor‐α (TNF‐α) production in lipopolysaccharides (LPS)‐induced RAW 264.7 macrophage cells. In this study, the mechanisms of DB on LPS‐induced NO production and cytokine expression through the activation of nuclear factor‐κB (NF‐κB) and ERK1/2 are demonstrated in RAW 264.7 cells. Through measurement with Griess's reagent, DB reduced NO level with an IC50 value of 2.85 ± 0.62 µM that was due to the significant suppression of LPS‐induced iNOS mRNA expression as well as IL‐1β, IL‐6, and IL‐10 mRNA at a concentration of 6 µM. At the signal transduction level, DB significantly inhibited NF‐κB binding activity, as determined using pNFκB‐Luciferase reporter system, which action resulted from the prevention of IκBα degradation. In addition, DB in the range of 1.5–6 µM significantly suppressed the activation of the ERK1/2 protein. In conclusion, the molecular mechanisms of DB on the inhibition of NO production and mRNA expression of iNOS, IL‐1β, IL‐6, and IL‐10 were due to the inhibition of the upstream kinases activation, which further alleviated the NF‐κB and MAPK/ERK signaling pathway in LPS‐induced RAW264.7 macrophage cells. J. Cell. Biochem. 109: 1057–1063, 2010. © 2010 Wiley‐Liss, Inc. |
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Keywords: | naphthofuranoxepin Dioscorea membranacea nitric oxide production inflammatory cytokines RAW 264 7 cells |
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