Maackiain is a novel antiallergic compound that suppresses transcriptional upregulation of the histamine H1 receptor and interleukin‐4 genes

Kujin contains antiallergic compounds that inhibit upregulation of histamine H1 receptor (H1R) and interleukin (IL)‐4 gene expression. However, the underlying mechanism remains unknown. We sought to identify a Kujin‐derived antiallergic compound and investigate its mechanism of action. The H1R and IL‐4 mRNA levels were determined by real‐time quantitative RT‐PCR. To investigate the effects of maackiain in vivo, toluene‐2,4‐diisocyanate (TDI)‐sensitized rats were used as a nasal hypersensitivity animal model. We identified (−)‐maackiain as the responsible component. Synthetic maackiain showed stereoselectivity for the suppression of IL‐4 gene expression but not for H1R gene expression, suggesting distinct target proteins for transcriptional signaling. (−)‐Maackiain inhibited of PKCδ translocation to the Golgi and phosphorylation of Tyr311 on PKCδ, which led to the suppression of H1R gene transcription. However, (−)‐maackiain did not show any antioxidant activity or inhibition of PKCδ enzymatic activity per se. Pretreatment with maackiain alleviated nasal symptoms and suppressed TDI‐induced upregulations of H1R and IL‐4 gene expressions in TDI‐sensitized rats. These data suggest that (−)‐maackiain is a novel antiallergic compound that alleviates nasal symptoms in TDI‐sensitized allergy model rats through the inhibition of H1R and IL‐4 gene expression. The molecular mechanism underlying its suppressive effect for H1R gene expression is mediated by the inhibition of PKCδ activation.

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