Department of Molecular Pharmacology, Institute of Health-Biosciences, The University of Tokushima Graduate School, Tokushima 770-8505, Japan.
Int Immunopharmacol. 2011 Nov;11(11):1766-72. doi: 10.1016/j.intimp.2011.07.003. Epub 2011 Jul 21.
Histamine plays major roles in allergic diseases and its action is mediated mainly by histamine H(1) receptor (H1R). We have demonstrated that histamine signaling-related H1R and histidine decarboxylase (HDC) genes are allergic diseases sensitive genes and their expression level affects severity of the allergic symptoms. Therefore, compounds that suppress histamine signaling should be promising candidates as anti-allergic drugs. Here, we investigated the effect of the extract from the bark of Albizia lebbeck (AL), one of the ingredients of Ayruvedic medicines, on H1R and HDC gene expression using toluene-2,4-diisocyanate (TDI) sensitized allergy model rats and HeLa cells expressing endogenous H1R. Administration of the AL extract significantly decreased the numbers of sneezing and nasal rubbing. Pretreatment with the AL extract suppressed TDI-induced H1R and HDC mRNA elevations as well as [(3)H]mepyramine binding, HDC activity, and histamine content in the nasal mucosa. AL extract also suppressed TDI-induced up-regulation of IL-4, IL-5, and IL-13 mRNA. In HeLa cells, AL extract suppressed phorbol-12-myristate-13-acetate- or histamine-induced up-regulation of H1R mRNA. Our data suggest that AL alleviated nasal symptoms by inhibiting histamine signaling in TDI-sensitized rats through suppression of H1R and HDC gene transcriptions. Suppression of Th2-cytokine signaling by AL also suggests that it could affect the histamine-cytokine network.
组氨酸在过敏疾病中起主要作用，其作用主要由组胺 H(1)受体（H1R）介导。我们已经证明，与组胺信号相关的 H1R 和组氨酸脱羧酶（HDC）基因是过敏疾病的敏感基因，其表达水平影响过敏症状的严重程度。因此，抑制组胺信号的化合物应该是有前途的抗过敏药物候选物。在这里，我们使用甲苯-2,4-二异氰酸酯（TDI）敏化过敏模型大鼠和表达内源性 H1R 的 HeLa 细胞，研究了从 Albizia lebbeck（AL）树皮提取物（一种阿育吠陀药物的成分）对 H1R 和 HDC 基因表达的影响。AL 提取物的给药显著减少了打喷嚏和鼻摩擦的次数。AL 提取物预处理可抑制 TDI 诱导的 H1R 和 HDC mRNA 升高以及鼻黏膜中[(3)H]mepyramine 结合、HDC 活性和组胺含量。AL 提取物还抑制了 TDI 诱导的 IL-4、IL-5 和 IL-13 mRNA 的上调。在 HeLa 细胞中，AL 提取物抑制佛波醇-12-肉豆蔻酸-13-乙酸酯或组胺诱导的 H1R mRNA 上调。我们的数据表明，AL 通过抑制 TDI 敏化大鼠中的 H1R 和 HDC 基因转录来抑制组胺信号，从而减轻了鼻症状。AL 对 Th2 细胞因子信号的抑制也表明它可能影响组胺-细胞因子网络。
