Exploring natural resources-derived compounds that suppress up-regulation of histamine H1 receptor gene expression as a diseases-sensitive gene

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We explored natural resources-derived compounds that suppress histamine H1R gene expression and identified (-)-maackiaain as one of the active compounds. H1R gene expression was mediated through the PKCδ/ERK/PARP-1 signaling pathway and translocation of PKCδto the Golgi in response to PMA stimulation was found to be very important for H1R gene expression in HeLa cells. We identified Hsp90 as a target protein for (-)-maackiain. (-)-Maackiain inhibited binding of PKCδto Hsp90 and suppressed PKCδtranslocation to the Golgi, resulting the suppression of H1R gene expression. Hsp90 inhibitors suppressed the up-regulation of H1R gene expression and alleviated allergic symptoms in allergy model rats.