当前位置: X-MOL 学术J. Nat. Med. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Effects of nicotinic acetylcholine receptor-activating alkaloids on anxiety-like behavior in zebrafish
Journal of Natural Medicines ( IF 3.3 ) Pub Date : 2021-07-15 , DOI: 10.1007/s11418-021-01544-8
Ainhoa Alzualde 1 , Oihane Jaka 1 , Diogo A R S Latino 2 , Omar Alijevic 2 , Iñaki Iturria 1 , Jorge Hurtado de Mendoza 3 , Pavel Pospisil 2 , Stefan Frentzel 2 , Manuel C Peitsch 2 , Julia Hoeng 2 , Kyoko Koshibu 2
Affiliation  

Alkaloids are a structurally complex group of natural products that have a diverse range of biological activities and significant therapeutic applications. In this study, we examined the acute, anxiolytic-like effects of nicotinic acetylcholine receptor (nAChR)-activating alkaloids with reported neuropharmacological effects but whose effects on anxiety are less well understood. Because α4β2 nAChRs can regulate anxiety, we first demonstrated the functional activities of alkaloids on these receptors in vitro. Their effects on anxiety-like behavior in zebrafish were then examined using the zebrafish novel tank test (NTT). The NTT is a relatively high-throughput behavioral paradigm that takes advantage of the natural tendency of fish to dive down when stressed or anxious. We report for the first time that cotinine, anatabine, and methylanatabine may suppress this anxiety-driven zebrafish behavior after a single 20-min treatment. Effective concentrations of these alkaloids were well above the concentrations naturally found in plants and the concentrations needed to induce anxiolytic-like effect by nicotine. These alkaloids showed good receptor interactions at the α4β2 nAChR agonist site as demonstrated by in vitro binding and in silico docking model, although somewhat weaker than that for nicotine. Minimal or no significant effect of other compounds may have been due to low bioavailability of these compounds in the brain, which is supported by the in silico prediction of blood–brain barrier permeability. Taken together, our findings indicate that nicotine, although not risk-free, is the most potent anxiolytic-like alkaloid tested in this study, and other natural alkaloids may regulate anxiety as well.



中文翻译:

烟碱型乙酰胆碱受体活化生物碱对斑马鱼焦虑样行为的影响

生物碱是一组结构复杂的天然产物,具有多种生物活性和重要的治疗应用。在这项研究中,我们检查了烟碱乙酰胆碱受体 (nAChR) 激活生物碱的急性、抗焦虑样作用,这些生物碱具有神经药理学作用,但其对焦虑的作用尚不清楚。因为 α4β2 nAChRs 可以调节焦虑,我们首先在体外证明了生物碱对这些受体的功能活性。然后使用斑马鱼新型水箱试验(NTT)检查它们对斑马鱼焦虑样行为的影响。NTT 是一种相对高通量的行为范式,它利用了鱼在压力或焦虑时下潜的自然趋势。我们首次报道了可替宁、新烟草碱、单次治疗 20 分钟后,甲基新竹碱可能会抑制这种由焦虑驱动的斑马鱼行为。这些生物碱的有效浓度远高于植物中天然存在的浓度以及尼古丁诱导类抗焦虑作用所需的浓度。这些生物碱在 α4β2 nAChR 激动剂位点显示出良好的受体相互作用,如体外结合和计算机对接模型所证明的那样,尽管比尼古丁的反应稍弱。其他化合物的最小或没有显着影响可能是由于这些化合物在大脑中的低生物利用度,这得到了血脑屏障通透性的计算机预测的支持。综上所述,我们的研究结果表明,尼古丁虽然不是无风险的,但却是本研究中测试的最有效的抗焦虑样生物碱,

更新日期:2021-07-15
down
wechat
bug