Department of Dermatology, University of Lübeck, Germany.
Int J Immunopathol Pharmacol. 2009 Oct-Dec;22(4):919-27. doi: 10.1177/039463200902200407.
Ambroxol is a widely used secretolytic agent originally developed from vasicine, a natural alkaloid found in Adhatoda vasica, extracts of which have been used to treat bronchitis, asthma, and rheumatism. We previously reported that ambroxol inhibits IgE-dependent mediator secretion from human mast cells and basophils, key effector cells of allergic inflammation. Here, the mechanisms involved in the inhibitory properties of ambroxol were assessed in comparison to other secretolytic analogues (e.g. vasicine, bromhexine, sputolysin). The results show that, in comparison to ambroxol, which reduced IgE-dependent histamine release from basophils at 10 microM-1 mM, the release of the amine was only moderately reduced by sputolysin and vasicine at 1 mM. In contrast, above 10 microM, bromhexine was found to be toxic to basophils in vitro as evidenced by induction of histamine release and reduced cell viability. In contrast, the inhibitory actions of ambroxol at concentrations below 1 mM were not toxic and entirely reversible. Ambroxol was also more potent than either sputolysin or vasicine in attenuating basophil IL-4 and IL-13 secretions, whereas bromhexine-induced suppression of de novo cytokine synthesis was due to toxic effects. Additionally, ambroxol reduced IgE-dependent p38 MAPK phosphorylation in basophils, unlike bromhexine, sputolysin and vasicine. These results clearly show that ambroxol is both more potent and effective at inhibiting IgE-dependent basophil mediator release and p38 MAPK activity than the other secretolytic analogues employed. The therapeutic potential of ambroxol as an anti-allergic agent is further underlined by these data.
氨溴索是一种广泛使用的黏液溶解剂，最初是从贝壳杉碱中开发出来的，贝壳杉碱是 Adhatoda vasica 中的一种天然生物碱，其提取物已被用于治疗支气管炎、哮喘和风湿病。我们之前报道过氨溴索抑制 IgE 依赖性介质从人肥大细胞和嗜碱性粒细胞中释放，这是过敏炎症的关键效应细胞。在这里，与其他黏液溶解类似物（如贝壳杉碱、溴己新、痰易净）相比，评估了氨溴索抑制特性的相关机制。结果表明，与 10 μM-1 mM 时可降低 IgE 依赖性组胺从嗜碱性粒细胞中释放的氨溴索相比，1 mM 时痰易净和贝壳杉碱仅适度降低胺的释放。相比之下，在 10 μM 以上，溴己新被发现对体外嗜碱性粒细胞具有毒性，表现为组胺释放诱导和细胞活力降低。相反，氨溴索在低于 1 mM 的浓度下的抑制作用没有毒性且完全可逆。氨溴索在减弱嗜碱性粒细胞 IL-4 和 IL-13 分泌方面也比痰易净或贝壳杉碱更有效，而溴己新诱导的新细胞因子合成抑制是由于毒性作用。此外，氨溴索可降低 IgE 依赖性 p38 MAPK 在嗜碱性粒细胞中的磷酸化，而溴己新、痰易净和贝壳杉碱则不然。这些结果清楚地表明，氨溴索在抑制 IgE 依赖性嗜碱性粒细胞介质释放和 p38 MAPK 活性方面比所使用的其他黏液溶解类似物更有效。这些数据进一步强调了氨溴索作为抗过敏药物的治疗潜力。
