Božičević Alen, De Mieri Maria, Nassenstein Christina, Wiegand Silke, Hamburger Matthias
Division of Pharmaceutical Biology, University of Basel , Klingelbergstrasse 50, CH-4056 Basel, Switzerland.
Institute of Anatomy and Cell Biology, Justus-Liebig-University , Aulweg 123, D-35385 Giessen, Germany.
J Nat Prod. 2017 Nov 22;80(11):2953-2961. doi: 10.1021/acs.jnatprod.7b00495. Epub 2017 Nov 7.
Plant pollens are strong airborne elicitors of asthma. Their proteinaceous allergens have been studied intensively, but little is known about a possible contribution of pollen secondary metabolites to the nonallergic exacerbation of asthma. Pollen samples originating from 30 plant species were analyzed by HPLC coupled to PDA, ESIMS, and ELSD detectors and off-line NMR spectroscopy. Polyamine conjugates, flavonoids, and sesquiterpene lactones were identified. Polyamine conjugates were characteristic of all Asteraceae species. The presence of sesquiterpene lactones in Asteraceae pollen varied between species and pollen lots. All plant pollen, including those from non-Asteraceae species, contained to some extent electrophiles as determined by their reaction with N-acetyl-l-cysteine. Selected pollen extracts and pure compounds were tested in murine afferent neurons and in murine tracheal preparations. Tetrahydrofuran extracts of Ambrosia artemisiifolia and Ambrosia psilostachya pollen and a mixture of sesquiterpene lactones coronopilin/parthenin increased the intracellular Ca concentration in 15%, 32%, and 37% of cinnamaldehyde-responsive neurons, respectively. In organ bath experiments, only the sesquiterpene lactones tested induced a weak dilatation of naïve tracheas and strongly lowered the maximal methacholine-induced tracheal constriction. A tetrahydrofuran extract of A. psilostachya and coronopilin/parthenin led to a time-dependent relaxation of the methacholine-preconstricted trachea. These results provide the first evidence for a potential role of pollen secondary metabolites in the modulation of the tracheal tone.
植物花粉是引发哮喘的强烈空气传播诱因。其蛋白质类过敏原已得到深入研究，但对于花粉次生代谢产物在哮喘非过敏性加重中可能起到的作用却知之甚少。采用高效液相色谱（HPLC）联用光电二极管阵列（PDA）、电喷雾离子化质谱（ESIMS）和蒸发光散射检测器（ELSD）以及离线核磁共振波谱法，对源自30种植物的花粉样本进行了分析。鉴定出了多胺共轭物、黄酮类化合物和倍半萜内酯。多胺共轭物是所有菊科植物花粉的特征成分。菊科植物花粉中倍半萜内酯的存在因物种和花粉批次而异。通过与N - 乙酰 - L - 半胱氨酸反应测定，所有植物花粉，包括非菊科植物的花粉，在一定程度上都含有亲电试剂。对选定的花粉提取物和纯化合物在小鼠传入神经元和小鼠气管制剂中进行了测试。豚草和糙果豚草花粉的四氢呋喃提取物以及倍半萜内酯冠突散囊菌素/小白菊内酯混合物分别使15%、32%和37%的对肉桂醛有反应的神经元细胞内钙浓度升高。在器官浴实验中，仅所测试的倍半萜内酯能引起未处理气管的微弱扩张，并显著降低最大乙酰甲胆碱诱导的气管收缩。糙果豚草的四氢呋喃提取物以及冠突散囊菌素/小白菊内酯能使乙酰甲胆碱预收缩的气管产生时间依赖性舒张。这些结果首次证明了花粉次生代谢产物在调节气管张力方面的潜在作用。
