Department of Pharmaceutical Sciences, Tshwane University of Technology, Private Bag X680, Pretoria, 0001, South Africa.
Department of Natural Products Chemistry, Medical University of Lublin, 1 Chodzki Street, 20-093, Lublin, Poland.
J Ethnopharmacol. 2022 May 23;290:115068. doi: 10.1016/j.jep.2022.115068. Epub 2022 Feb 5.
Mesembryanthemum tortuosum L. (previously known as Sceletium tortuosum (L.) N.E. Br.) is indigenous to South Africa and traditionally used to alleviate anxiety, stress and depression. Mesembrine and its alkaloid analogues such as mesembrenone, mesembrenol and mesembranol have been identified as the key compounds responsible for the reported effects on the central nervous system.
To investigate M. tortuosum alkaloids for possible anxiolytic-like effects in the 5-dpf in vivo zebrafish model by assessing thigmotaxis and locomotor activity.
Locomotor activity and reverse-thigmotaxis, recognised anxiety-related behaviours in 5-days post fertilization zebrafish larvae, were analysed under simulated stressful conditions of alternating light-dark challenges. Cheminformatics screening and molecular docking were also performed to rationalize the inhibitory activity of the alkaloids on the serotonin reuptake transporter, the accepted primary mechanism of action of selective serotonin reuptake inhibitors. Mesembrine has been reported to have inhibitory effects on serotonin reuptake, with consequential anti-depressant and anxiolytic effects.
All four alkaloids assessed decreased the anxiety-related behaviour of zebrafish larvae exposed to the light-dark challenge. Significant increases in the percentage of time spent in the central arena during the dark phase were also observed when larvae were exposed to the pure alkaloids (mesembrenone, mesembrenol, mesembrine and mesembrenol) compared to the control. However, mesembrenone and mesembranol demonstrated a greater anxiolytic-like effect than the other alkaloids. In addition to favourable pharmacokinetic and physicochemical properties revealed via in silico predictions, high-affinity interactions characterized the binding of the alkaloids with the serotonin transporter.
M. tortuosum alkaloids demonstrated an anxiolytic-like effect in zebrafish larvae providing evidence for its traditional and modern day use as an anxiolytic.
Mesembryanthemum tortuosum L.（以前称为 Sceletium tortuosum (L.) N.E. Br.）原产于南非，传统上用于缓解焦虑、压力和抑郁。已鉴定出 mesembrine 及其生物碱类似物，如 mesembrenone、mesembrenol 和 mesembranol，是负责报告的对中枢神经系统影响的关键化合物。
通过评估触壁和运动活性，研究 M. tortuosum 生物碱在活体斑马鱼 5 天龄幼虫模型中是否具有抗焦虑样作用。
在模拟光暗挑战的应激条件下，分析运动活性和反向触壁，这是 5 天龄斑马鱼幼虫的公认焦虑相关行为。还进行了计算化学筛选和分子对接，以合理化生物碱对 5-羟色胺再摄取转运体的抑制活性，5-羟色胺再摄取转运体是选择性 5-羟色胺再摄取抑制剂的公认主要作用机制。据报道，mesembrine 对 5-羟色胺再摄取具有抑制作用，具有抗抑郁和抗焦虑作用。
在所评估的四种生物碱中，所有生物碱都降低了暴露于光暗挑战的斑马鱼幼虫的焦虑相关行为。当幼虫暴露于纯生物碱（mesembrenone、mesembrenol、mesembrine 和 mesembrenol）时，与对照相比，在暗期花费的时间百分比也显著增加。然而，mesembrenone 和 mesembranol 表现出比其他生物碱更强的抗焦虑样作用。除了通过计算预测揭示的有利药代动力学和物理化学性质外，生物碱与 5-羟色胺转运体的结合还具有高亲和力相互作用。
M. tortuosum 生物碱在斑马鱼幼虫中表现出抗焦虑样作用，为其作为抗焦虑药的传统和现代用途提供了证据。
