title: Maackiain is a novel antiallergic compound that suppresses transcriptional upregulation of the histamine H1 receptor and interleukin-4 genes.
abstract: 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 Tyr(311) 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.
authors.affiliation: Department of Molecular Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School 1-78-1 Sho-machi, Tokushima, 770-8505, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mizuguchi
authors.affiliation: Department of Molecular Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School 1-78-1 Sho-machi, Tokushima, 770-8505, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nariai
authors.affiliation: Department of Molecular Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School 1-78-1 Sho-machi, Tokushima, 770-8505, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Kato
authors.affiliation: Department of Molecular Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School 1-78-1 Sho-machi, Tokushima, 770-8505, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nakano
authors.affiliation: Department of Molecular Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School 1-78-1 Sho-machi, Tokushima, 770-8505, Japan.
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Kanayama
authors.affiliation: Department of Pharmacognosy, Institute of Biomedical Sciences, Tokushima University Graduate School 1-78-1 Sho-machi, Tokushima, 770-8505, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kashiwada
authors.affiliation: Department of Pharmaceutical Chemistry, Institute of Biomedical Sciences, Tokushima University Graduate School 1-78-1 Sho-machi, Tokushima, 770-8505, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Nemoto
authors.affiliation: Department of Clinical Pharmacy, Institute of Biomedical Sciences, Tokushima Tokushima University Graduate School 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kawazoe
authors.affiliation: Department of Pharmacognosy, Institute of Biomedical Sciences, Tokushima University Graduate School 1-78-1 Sho-machi, Tokushima, 770-8505, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Takaishi
authors.affiliation: Department of Otolaryngology, Institute of Biomedical Sciences, Tokushima University Graduate School 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kitamura
authors.affiliation: Department of Otolaryngology, Institute of Biomedical Sciences, Tokushima University Graduate School 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Takeda
authors.affiliation: Department of Molecular Studies for Incurable Diseases, Institute of Biomedical Sciences, Tokushima University Graduate School 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fukui
keywords: Allergic disease sensitive gene; IL-4 gene; Kujin; PKC δ; histamine H1 receptor gene; maackiain