Kujin Suppresses Histamine Signaling at the Transcriptional Level in Toluene 2,4-Diisocyanate–Sensitized Rats

Shrabanti Dev; Hiroyuki Mizuguchi; Asish K. Das; Kazutaka Maeyama; Shiho Horinaga; Shuhei Kato; Misaki Tamada; Masashi Hattori; Hayato Umehara; Hiroyuki Fukui

doi:10.1254/jphs.09003FP

Full Papers

Kujin Suppresses Histamine Signaling at the Transcriptional Level in Toluene 2,4-Diisocyanate–Sensitized Rats

Shrabanti Dev, Hiroyuki Mizuguchi, Asish K. Das, Kazutaka Maeyama, Shiho Horinaga, Shuhei Kato, Misaki Tamada, Masashi Hattori, Hayato Umehara, Hiroyuki Fukui

Author information

Shrabanti Dev
Department of Molecular Pharmacology, Institute of Health-Biosciences, The University of Tokushima Graduate School, Japan
Hiroyuki Mizuguchi
Department of Molecular Pharmacology, Institute of Health-Biosciences, The University of Tokushima Graduate School, Japan
Asish K. Das
Department of Molecular Pharmacology, Institute of Health-Biosciences, The University of Tokushima Graduate School, Japan
Kazutaka Maeyama
Division of Pharmacology, Department of Integrated Basic Medical Science, Ehime University School of Medicine, Japan
Shiho Horinaga
Department of Molecular Pharmacology, Institute of Health-Biosciences, The University of Tokushima Graduate School, Japan
Shuhei Kato
Department of Molecular Pharmacology, Institute of Health-Biosciences, The University of Tokushima Graduate School, Japan
Misaki Tamada
Department of Molecular Pharmacology, Institute of Health-Biosciences, The University of Tokushima Graduate School, Japan
Masashi Hattori
Department of Molecular Pharmacology, Institute of Health-Biosciences, The University of Tokushima Graduate School, Japan
Hayato Umehara
Department of Molecular Pharmacology, Institute of Health-Biosciences, The University of Tokushima Graduate School, Japan
Hiroyuki Fukui
Department of Molecular Pharmacology, Institute of Health-Biosciences, The University of Tokushima Graduate School, Japan

Keywords: allergy, histamine H₁ receptor, histamine signaling, histidine decarboxylase, Kujin

JOURNAL FREE ACCESS

2009 Volume 109 Issue 4 Pages 606-617

DOI https://doi.org/10.1254/jphs.09003FP

View "Advance Publication" version (April 7, 2009).

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Abstract

Kujin, the dried root of Sophorae flavescensis, has been used in Chinese folklore medicine against allergy. Evaluation of its anti-allergic potential as well as its mechanism of action has rarely been established. We investigated the effect of Kujin on toluene-2,4-diisocyanate (TDI)-induced allergic behavior and related histamine signaling including mRNA levels of histamine H₁ receptor (H1R) and histidine decarboxylase (HDC), H1R and HDC activities, and histamine content in rat nasal mucosa. We also investigated the effect of Kujin on the mRNA levels of helper T cell type 2 (Th2)-cytokine genes closely related to histamine signaling. TDI provocation caused acute allergic symptoms accompanied with up-regulations of H1R and HDC mRNAs and increases in HDC activity, histamine content, and [³H]mepyramine binding activity in the nasal mucosa, all of which were significantly suppressed by pretreatment with Kujin for 3 weeks. Kujin also suppressed the TDI-induced IL-4 and IL-5 mRNA elevations. These data suggest that oral administration of Kujin showed anti-allergic activity through suppression of histamine signaling by the inhibition of TDI-induced H1R and HDC mRNA elevations followed by decrease in H1R, HDC protein level, and histamine content in the nasal mucosa of TDI-sensitized rats. Suppression of Th2-cytokine signaling by Kujin also suggests that it could affect the histamine-cytokine network.

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