It is widely recognized that an alteration in membrane physical properties induced by the adsorption of various drugs and biologically active compounds might greatly affect the functioning of peptides and proteins embedded in the membrane, in particular various ion channels. This study aimed to obtain deep insight into the diversity of the molecular mechanisms of membrane action of one of the most numerous and extremely important class of phytochemicals, the alkaloids. Protoalkaloids (derivatives of β-phenylethylamine, benzylamines, and colchicines), heterocyclic alkaloids (derivatives of purine, quinolysidine, piperidine, pyridine, quinoline, and isoquinoline), and steroid alkaloids were tested. We evaluated the effects of 22 compounds on lipid packing by investigating the thermotropic behavior of membrane lipids and the leakage of a fluorescent marker from unilamellar lipid vesicles. The alteration in the transmembrane distribution of the electrical potential was estimated by measuring the alkaloid induced changes in the boundary potential of planar lipid bilayers. We found that benzylamines, the chili pepper active components, capsaicin and dihydrocapsaicin, strongly affect not only the elastic properties of the lipid host, but also its electrostatics by dramatic decrease in membrane dipole potential. We concluded that the increase in the conductance and lifetime of gramicidin A channels induced by benzylamines was related to alteration in membrane dipole potential not to decrease in membrane stiffness. A sharp decrease in the lifetime of single ion pores induced by the antifungal lipopeptide syringomycin E, after addition of benzylamines and black pepper alkaloid piperine, was also mainly due to the reduction in dipole potential. At the same time, we showed that the disordering of membrane lipids in the presence of benzylamines and piperine plays a decisive role in the regulation of the conductance induced by the antifungal polyene macrolide antibiotic nystatin, while the inhibition of steady-state transmembrane current produced by the antimicrobial peptide cecropin A was attributed to both the dipole potential drop and membrane lipid disordering in the presence of pepper alkaloids. These data might lead to a better understanding of the biological activity of alkaloids, especially their action on voltage-gated and mechanosensitive ion channels in cell membranes.

广泛认识到，由各种药物和生物活性化合物的吸附引起的膜物理性质的改变可能极大地影响包埋在膜中的肽和蛋白质，特别是各种离子通道的功能。这项研究旨在深入了解植物化学物质种类最多，最重要的一类-生物碱-的膜作用分子机制的多样性。测试了原生物碱（β-苯乙胺，苄胺和秋水仙碱的衍生物），杂环生物碱（嘌呤，奎尼丁，哌啶，吡啶，喹啉和异喹啉的衍生物）和甾体生物碱。我们通过调查膜脂的热致行为和单层脂质囊泡中荧光标记的渗漏，评估了22种化合物对脂质堆积的影响。通过测量生物碱引起的平面脂质双层边界电势的变化来估计电势的跨膜分布的变化。我们发现苄胺，辣椒的活性成分，辣椒素和二氢辣椒素不仅会极大地影响脂质宿主的弹性，而且还会通过膜偶极子电位的急剧降低而强烈影响其静电。我们得出的结论是，苄胺诱导的短杆菌肽A通道的电导率和寿命的增加与膜偶极电位的改变而不是膜刚度的降低有关。加入苄胺和黑胡椒生物碱胡椒碱后，由抗真菌脂肽丁香霉素E诱导的单离子孔寿命的急剧减少也主要是由于偶极电位的降低。同时，我们表明在存在苄胺和胡椒碱的情况下，膜脂的紊乱在调节抗真菌多烯大环内酯抗生素制霉菌素诱导的电导中起决定性作用，而对由其产生的稳态跨膜电流的抑制作用抗菌肽天蚕素A归因于胡椒生物碱存在下的偶极电位下降和膜脂紊乱。这些数据可能有助于更好地了解生物碱的生物活性，