Kim Sang-Hyun, Kim Sug-Hyun, Kim Sung-Hwa, Moon Jin-Young, Park Won-Hwan, Kim Cheorl-Ho, Shin Tae-Yong
Department of Pharmacology, Kyungpook National University Medical School, Daegu, South Korea.
Biol Pharm Bull. 2006 Mar;29(3):494-8. doi: 10.1248/bpb.29.494.
The discovery of drugs for the treatment of allergic disease is an important subject in human health. Stimulation of mast cells starts the process of degranulation resulting in releasing of mediators, such as histamine. In this report, we investigated the effect of aqueous extract of Dracocephalum argunense Fisch. (Labiatae) (DAAE) on the mast cell-mediated allergic response and studied its possible mechanisms of action, focusing on the histamine release and pro-inflammatory cytokine secretion in mast cells. DAAE inhibited compound 48/80-induced systemic reactions and serum histamine release in mice. In addition, DAAE attenuated IgE-mediated skin allergic reaction. DAAE dose-dependently reduced IgE-induced histamine release from mast cells. The level of cAMP was transiently increased by treatment of DAAE. DAAE specifically blocked the phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-induced p38 mitogen-activated protein kinase (MAPK) activation. DAAE decreased the secretion of pro-inflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-6 in mast cells. Our findings provide evidence that DAAE inhibits mast cell derived allergic reactions, and involvement of cAMP for histamine release and p38 MAPK for pro-inflammatory cytokine secretion in these effects.
发现治疗过敏性疾病的药物是人类健康领域的一个重要课题。肥大细胞的激活启动了脱颗粒过程,导致组胺等介质的释放。在本报告中,我们研究了白花枝子花(唇形科)水提取物(DAAE)对肥大细胞介导的过敏反应的影响,并研究了其可能的作用机制,重点关注肥大细胞中组胺释放和促炎细胞因子分泌。DAAE抑制了化合物48/80诱导的小鼠全身反应和血清组胺释放。此外,DAAE减轻了IgE介导的皮肤过敏反应。DAAE剂量依赖性地减少了IgE诱导的肥大细胞组胺释放。DAAE处理可使cAMP水平短暂升高。DAAE特异性阻断佛波酯12-肉豆蔻酸酯13-乙酸酯(PMA)加钙离子载体A23187诱导的p38丝裂原活化蛋白激酶(MAPK)激活。DAAE减少了肥大细胞中促炎细胞因子如肿瘤坏死因子-α和白细胞介素-6的分泌。我们的研究结果提供了证据,证明DAAE抑制肥大细胞衍生的过敏反应,以及cAMP参与组胺释放和p38 MAPK参与这些效应中的促炎细胞因子分泌。