Differential Interaction of Cannabidiol with Biomembranes Dependent on Cholesterol Concentration
Differential Interaction of Cannabidiol with Biomembranes Dependent on Cholesterol Concentration
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大麻二酚与生物膜的差异相互作用取决于胆固醇浓度
DOI：
10.1021/acschemneuro.2c00040
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发表时间：
2022
影响因子：
5
通讯作者：
Lee, Sunghee
中科院分区：
文献类型：
--
作者：
Perez, Escarlin;Ceja-Vega, Jasmin;Krmic, Michael;Gamez Hernandez, Alondra;Gudyka, Jamie;Porteus, Riley;Lee, Sunghee
大麻二酚（CBD）是植物源大麻素的主要非精神活性成分，据报道对中枢神经系统（CNS）具有广泛的潜在有益药理作用。在这项研究中，液滴界面双层，一个模型细胞膜，被用来研究CBD对被动水渗透性，一个基本的膜生物物理特性的影响。CBD的存在降低了由1，2-二油酰基-sn-甘油-3-磷酸胆碱（DOPC）和在DOPC中低浓度的胆固醇（Chol）（20 mol %）组成的模型脂质膜的水渗透性，而当存在较高浓度的Chol（33 mol %）时，CBD具有相反的作用，增加了水渗透性。在水的渗透性变化的直径效应后，除了胆固醇低和胆固醇高双层CBD表示一个变量的相互作用，取决于双层包装和流动性的初始状态的CBD。此外，差示扫描量热法研究提供的证据表明，CBD与DOPC和DOPC/Chol膜的热致行为分别存在选择性变化，这支持CBD依赖于胆固醇的这些不同的膜相互作用。CBD在改变物理性质中敏感地响应膜Chol浓度的有趣能力突出了CBD可以对异质生物膜（包括CNS的生物膜）产生的显著影响，CNS的神经元富含Chol，达到身体总Chol的四分之一在大脑中的程度，并且有缺陷的大脑Chol稳态与神经退行性疾病有关。
Cannabidiol (CBD), the major nonpsychoactive component of plant-derived cannabinoids, has been reported to have a broad range of potential beneficial pharmacological effects on the central nervous system (CNS). In this study, the droplet interface bilayer, a model cell membrane, is used to examine the effects of CBD on passive water permeability, a fundamental membrane biophysical property. The presence of CBD decreases the water permeability of model lipid membranes composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and at low concentrations of cholesterol (Chol) (20 mol %) in DOPC, whereas when higher concentrations of Chol are present (33 mol %), CBD has an opposing effect, increasing water permeability. The diametric effect in water permeability change upon addition of CBD to Chol-low and Chol-high bilayers signifies a variant interaction of CBD, depending on the initial state of bilayer packing and fluidity. Additionally, differential scanning calorimetry studies provide evidence that there are selective changes in thermotropic behavior for CBD with DOPC and with DOPC/Chol membranes, respectively, supportive of these varying membrane interactions of CBD dependent upon cholesterol. The intriguing ability of CBD to sensitively respond to membrane Chol concentrations in modifying physical properties highlights the significant impact that CBD can have on heterogeneous biomembranes including those of the CNS, the neurons of which are enriched in Chol to a point where up to a quarter of the body’s total Chol is in the brain, and defective brain Chol homeostasis is implicated in neurodegenerative diseases.