Effect of wild grape on the signaling of histamine H<sub>1</sub> receptor gene expression responsible for the pathogenesis of allergic rhinitis

  • Islam Rezwanul
    Department of Molecular Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School
  • Mizuguchi Hiroyuki
    Laboratory of Pharmacology Faculty of Pharmacy Osaka Ohtani University
  • Shaha Aurpita
    Department of Molecular Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School
  • Nishida Kohei
    Department of Molecular Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School
  • Yabumoto Masami
    Medical Corporation Kinshukai
  • Ikeda Hisashi
    Nab co., ltd.
  • Fujino Hiromichi
    Department of Molecular Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School
  • Kitamura Yoshiaki
    Department of Otolaryngology, Institute of Biomedical Sciences, Tokushima University Graduate School
  • Fukui Hiroyuki
    Department of Molecular Studies for Incurable Diseases, Institute of Biomedical Sciences, Tokushima University Graduate School
  • Takeda Noriaki
    Department of Otolaryngology, Institute of Biomedical Sciences, Tokushima University Graduate School

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  • Effect of wild grape on the signaling of histamine H1 receptor gene expression responsible for the pathogenesis of allergic rhinitis

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Abstract

<p>As expression level of allergic disease‐sensitive genes are correlated with allergic symptom severity, suppression of these gene expressions could be good therapeutics. We have demonstrated that PKCδ signaling and NFAT signaling, involve in histamine H1 receptor (H1R) and IL‐9 gene expressions, respectively, are responsible for the pathogenesis of allergic rhinitis. We explore anti‐allergic compounds that suppress these signaling pathways and found that wild grape (WG) contains such compounds. Here, we investigated the effect of WG hot water extract (WGE) on the signaling pathways for PKCδ‐mediated H1R and NFAT‐mediated IL‐9 gene expressions. WGE suppressed histamine/PMA‐induced H1R gene up‐regulation in HeLa cells. Toluene‐2,4‐diisocyanate (TDI)‐induced H1R mRNA elevation in TDI‐sensitized rats was also suppressed by WGE treatment. Treatment with WGE in combination with Awa‐tea, suppresses NFAT signaling‐mediated IL‐9 gene, markedly alleviated nasal symptoms. Furthermore, WGE suppressed PMA‐induced IL‐33 gene up‐regulation in Swiss 3T3 cells. Data suggest that combination of WGE, suppresses PKCδ signaling with Awa‐tea, suppresses NFAT signaling would have distinct clinical and therapeutic advantages as a substitute for anti‐allergic drugs. In addition, as the expression level of IL‐33 mRNA was correlated with the blood eosinophils number in patients with pollinosis, WG could alleviate eosinophilic inflammation through the suppression of IL‐33 gene expression. J. Med. Invest. 65:242‐250, August, 2018</p>

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