Dehydrocorydaline induced antidepressant-like effect in a chronic unpredictable mild stress mouse model via inhibiting uptake-2 monoamine transporters
Dehydrocorydaline induced antidepressant-like effect in a chronic unpredictable mild stress mouse model via inhibiting uptake-2 monoamine transporters
复制标题
脱氢紫堇碱通过抑制摄取 2 单胺转运蛋白在慢性不可预测的轻度应激小鼠模型中诱导抗抑郁样作用
DOI：
10.1016/j.ejphar.2019.172725
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发表时间：
2019-12-01
影响因子：
5
通讯作者：
Zhou, Hui
中科院分区：
文献类型：
--
作者：
Jin, Lisha;Zhou, Sisi;Zhou, Hui
去氢延胡索碱是延胡索中的一种活性生物碱类化合物。T.王.我们在慢性不可预测的轻度应激小鼠模型中发现脱氢肾上腺素诱导的抗抑郁样作用，但确切的机制尚未得到解决。我们推测脱氢皮质醇可能通过抑制脑内单胺转运体而具有抗抑郁作用。我们通过检测慢性不可预测的轻度应激小鼠前额叶皮层单胺递质（5-HT，NE和DA）的水平来评估脱氢皮质醇的作用机制。然后，我们使用细胞模型和小鼠突触体来研究这些行为的分子和细胞机制以及脱氢皮质醇引起的单胺改变。我们的研究结果表明，脱氢皮质醇影响单胺递质的浓度，降低周转率，这表明增加神经元的活动。其可能的机制是脱氢肾上腺皮质素能有效地抑制摄取-2转运体（IC_（50）为0.1-4 μ M），并能抑制突触体对5-HT/DA/NE的再摄取。这些数据表明，脱氢肾上腺素具有抗抑郁作用，这可能与通过抑制摄取-2转运蛋白改变脑中单胺的含量有关。
Dehydrocorydaline, is an active alkaloid compound in Corydalis yanhusuo W. T. Wang. We found dehydrocorydaline induced antidepressant-like effects in a chronic unpredictable mild stress mouse model, but the exact mechanisms have not been addressed. We speculated that dehydrocorydaline may have an antidepressant effect via inhibiting monoamine transporters in the brain. We evaluated the mechanism of action of dehydrocorydaline by examining the levels of monoamine transmitters (5-HT, NE and DA) in the prefrontal cortex in chronic unpredictable mild stress mice. Then, we used cell models and the mouse synaptosome to study molecular and cellular mechanisms underlying these behaviors and monoamine alterations by dehydrocorydaline. Our results indicated that dehydrocorydaline affects the concentrations of monoamine transmitters and decreases the turnover ratio, which indicates increased neuronal activity. The possible mechanism is that dehydrocorydaline potently inhibits uptake-2 transporters with the IC50 values of 0.1-4 mu M and could inhibit the reuptake of 5-HT/DA/NE in the synaptosome. These data suggest that dehydrocorydaline has an antidepressant effect that is likely related to changing the content of monoamines in the brain by inhibiting uptake-2 transporters.