Luteolin shows antidepressant-like effect by inhibiting and downregulating plasma membrane monoamine transporter (PMAT, Slc29a4)
Luteolin shows antidepressant-like effect by inhibiting and downregulating plasma membrane monoamine transporter (PMAT, Slc29a4)
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木犀草素通过抑制和下调质膜单胺转运蛋白（PMAT、Slc29a4）显示出抗抑郁样作用
DOI：
10.1016/j.jff.2019.01.048
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发表时间：
2019-03
影响因子：
5.6
通讯作者：
Zhou Hui
中科院分区：
文献类型：
--
作者：
Zhu Shujie;Lei Shaowei;Zhou Sisi;Jin Lisha;Zeng Su;Jiang Huidi;Zhou Hui
木犀草素是一种重要的植物雌激素，具有抗抑郁作用，存在于许多食物中。我们的目的是澄清潜在的抗抑郁机制毛地黄黄酮对PMAT与单胺假说。结果发现，rPmat在边缘系统有高表达，在孕鼠和非孕鼠中表达差异显著，在慢性不可预见性轻度应激小鼠中表达呈上升趋势。在稳定转染细胞模型中的结果表明，木犀草素是单胺转运体的抑制剂。在C6细胞和原代海马神经元中进一步研究发现，木犀草素主要通过雌激素β受体（ERβ）和脑源性神经营养因子（BDNF）的表达显著降低PMAT。PMAT的这些结果也在卵巢切除抑郁大鼠中得到证实。结论：毛地黄黄酮可直接或间接抑制5-羟色胺重摄取，导致突触间隙单胺类神经递质增加。这些结果通过PMAT揭示了木犀草素的抗抑郁作用机制。
Luteolin is an important phytoestrogen with antidepressant effects found in many foods. We aimed to clarify the underlying antidepressant mechanisms of luteolin on PMAT associated with the monoamine hypothesis. We found rPmat had high expression in the limbic system, significant differences in mRNA expression between the pregnant and non-pregnant rats and an upward trend in mice with chronic unpredictable mild stress (CUMS). The results in the stably transfected cell models demonstrated that luteolin was the inhibitor of monoamine transporters. Further studies in C6 cells and primary hippocampal neurons revealed luteolin significantly downgraded PMAT mainly through the oestrogen β receptor (ERβ) and upgraded brain-derived neurotrophic factor (BDNF) expression. These results for PMAT have also been demonstrated in ovariectomized depressed rats. In conclusion, luteolin could directly and indirectly inhibit serotonin reuptake, resulting in an increase in monoamine neurotransmitters in the synaptic cleft. These findings manifest the antidepressant mechanisms of luteolin through PMAT.
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