Platycladus orientalis seed extract as a potential triple reuptake MAO inhibitor rescue depression phenotype through restoring monoamine neurotransmitters
Platycladus orientalis seed extract as a potential triple reuptake MAO inhibitor rescue depression phenotype through restoring monoamine neurotransmitters
复制标题
侧柏种子提取物作为潜在的三重再摄取 MAO 抑制剂，通过恢复单胺神经递质来拯救抑郁症表型
DOI：
10.1016/j.jep.2022.115302
复制
发表时间：
2022-09-15
影响因子：
5.4
通讯作者：
Su，Weiwei
中科院分区：
文献类型：
--
作者：
Yan，Li;Wang，Jiawei;Su，Weiwei
民族药理学相关性在《神农本草经》、《本草纲目》等文献中，都有关于侧柏种子用于调节情绪和体力活动的记载。最近，本研究通过分离、鉴定其提取物成分，探讨其改善单胺类神经递质功能治疗抑郁症的作用机制，为临床应用提供理论依据。P. orientalis（S4）在慢性、不可预测的、轻度应激（MISS）诱导的大鼠模型中拯救抑郁行为。材料和方法我们使用超快速液相色谱结合三重四极杆-飞行时间串联质谱分析S4中的化学成分。利用斑马鱼实验平台和分子对接技术分析S4是否调控静息/觉醒行为，并预测与单胺类神经递质相关的生物学靶点。采用抑郁行为学实验（体重、蔗糖偏好实验、悬尾实验、强迫游泳实验）对模型进行研究。经行为学测试和处死后，将大鼠脑分为海马、前沿皮层和中缝背核。采用快速液相色谱-三重四极杆串联质谱联用技术测定了这三个脑区的主要单胺类神经递质及其代谢产物的含量。结果在S4中鉴定出41种化合物，包括脂肪酸、萜类、氨基酸、植物甾醇和黄酮类。S4可增加斑马鱼的总休息时间，降低其觉醒活动。S4与肾上腺素激动剂、5-羟色胺（5-HT）再摄取抑制剂和多巴胺激动剂高度相关。与对照组相比，实验组大鼠体重明显减轻，对蔗糖水的偏好性增加，而尾部悬吊试验和强迫游泳试验中的不动时间增加。S4可以显着拯救5-HT，去甲肾上腺素和多巴胺在前额叶皮层和中缝背核nucleus.ConclusionsWe证明，S4是一个潜在的抑制剂，可以挽救抑郁症的抑郁症模型大鼠恢复单胺类神经递质在不同的脑区。
Ethnopharmacology relevancePlatycladus orientalisseeds are recorded in traditional Chinese medicine (TCM) formulations for modulation of mood and physical activity in “Shen Nong Ben Cao Jing” and “Compendium of Materia Medica” and so on. Recently, we identified its extracting components and looked for the potentials in treatment for depression by improving the function of monoamine neurotransmitters.Aim of the studyWe investigated the mechanism of action of the seed extracts ofP. orientalis(S4) to rescue depressive behavior in a chronic, unpredicted, mild stress (CUMS)-induced model in rats.Materials and methodsWe used ultra-fast liquid chromatography coupled with triple quadrupole-time of flight tandem mass spectrometry to analyze the chemical constituents in S4. An assay platform in zebrafish and molecular docking were used to analyze if S4 regulated rest/wake behavior and predict the biological targets which correlated with monoamine neurotransmitters. Depressive-behavior tests (body weight, sucrose preference test, tail-suspension test, forced-swimming test) were carried in the CUMS model. After behavior tests and killing, rat brains were separated into the hippocampus, frontier cortex and dorsal raphe nucleus. The main monoamine neurotransmitters and their metabolite concentrations in these three brain regions were measured by rapid resolution liquid chromatography coupled with triple quadrupole tandem mass spectrometry.ResultsForty-one compounds were identified in S4, including fatty acids, terpenoids, amino acids, plant sterols and flavonoids. S4 could increase the total rest time and decrease the waking activity of zebrafish. S4 showed high correlation with adrenaline agonists, 5-hydroxytryptamine (5-HT) reuptake inhibitors and dopamine agonists. CUMS-group rats, compared with controls, had significantly decreased body weight and preference for sucrose water, whereas the immobility time in the tail-suspension test and forced-swimming test was increased. S4 could significantly rescue the increased levels of 5-HT, noradrenaline and dopamine in the prefrontal cortex and dorsal raphe nucleus.ConclusionsWe demonstrated that S4 was a potential inhibitor of MAO reuptake that could rescue depression in a CUMS-model rats by restoring monoamine neurotransmitters in different encephalic regions.