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苦参碱在2,4-二异氰酸甲苯酯致敏大鼠中,于转录水平抑制组胺信号传导。

Kujin suppresses histamine signaling at the transcriptional level in toluene 2,4-diisocyanate-sensitized rats.

作者信息

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

机构信息

Department of Molecular Pharmacology, Institute of Health-Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.

出版信息

J Pharmacol Sci. 2009 Apr;109(4):606-17. doi: 10.1254/jphs.09003fp. Epub 2009 Apr 7.

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 H(1) 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 [(3)H]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.

摘要

苦参,即苦参的干燥根,在中国民间医学中被用于抗过敏。其抗过敏潜力及其作用机制的评估却鲜有定论。我们研究了苦参对甲苯 - 2,4 - 二异氰酸酯(TDI)诱导的过敏行为以及相关组胺信号传导的影响,包括组胺H(1)受体(H1R)和组氨酸脱羧酶(HDC)的mRNA水平、H1R和HDC活性以及大鼠鼻黏膜中的组胺含量。我们还研究了苦参对与组胺信号传导密切相关的辅助性T细胞2型(Th2)细胞因子基因mRNA水平的影响。TDI激发引起急性过敏症状,同时伴有鼻黏膜中H1R和HDC mRNA上调,HDC活性、组胺含量以及[(3)H]美吡拉敏结合活性增加,而预先用苦参处理3周可显著抑制所有这些变化。苦参还抑制了TDI诱导的IL - 4和IL - 5 mRNA升高。这些数据表明,口服苦参通过抑制TDI诱导的H1R和HDC mRNA升高,进而降低TDI致敏大鼠鼻黏膜中H1R、HDC蛋白水平和组胺含量,从而抑制组胺信号传导,显示出抗过敏活性。苦参对Th2细胞因子信号传导的抑制也表明它可能影响组胺 - 细胞因子网络。

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