单胺类神经递质
行为绝望测验
药理学
化学
多巴胺
再摄取抑制剂
抗抑郁药
血清素
内科学
医学
生物
生物化学
海马体
受体
作者
Yan Li,Jiawei Wang,Xiang He,Yufan Jin,Pan Chen,Yang Bai,Peibo Li,Weiwei Sui
标识
DOI:10.1016/j.jep.2022.115302
摘要
Platycladus orientalis seeds 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. We investigated the mechanism of action of the seed extracts of P. orientalis (S4) to rescue depressive behavior in a chronic, unpredicted, mild stress (CUMS)-induced model in rats. We 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. Forty-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. We 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.
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