Jatrorrhizine reduces 5-HT and NE uptake via inhibition of uptake-2 transporters and produces antidepressant-like action in mice
Jatrorrhizine reduces 5-HT and NE uptake via inhibition of uptake-2 transporters and produces antidepressant-like action in mice
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药根碱通过抑制摄取 2 转运蛋白减少 5-HT 和 NE 摄取，并在小鼠中产生抗抑郁样作用
DOI：
10.1080/00498254.2018.1542188
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发表时间：
2019-01
期刊：
影响因子：
1.8
通讯作者：
Zhou Hui
中科院分区：
文献类型：
--
作者：
Sun Siyuan;Zhou Sisi;Lei Shaowei;Zhu Shujie;Wang Kai;Jiang Huidi;Zhou Hui
摘要1.药根碱是在各种传统中药植物中发现的活性成分。基于我们以前的发现，药根碱是一个有效的抑制剂的OCT 2和OCT 3，本研究的目的是探讨药根碱是否有抗抑郁样作用通过抑制摄取2转运蛋白。2.体外摄取试验表明，药根碱强烈抑制PMAT介导的MPP+摄取，IC 50值为1.05 μM，并降低hOCT 2、hOCT 3和hPMAT介导的5-HT和NE摄取，IC 50值为0.1-1 μM（OCT 2和OCT 3）和1-10 μM（PMAT）。3.在小鼠突触体中，药根碱以浓度依赖性方式抑制5-HT和NE摄取，其中摄取-2抑制作用显著。4.采用小鼠悬尾试验（TST）评价药根碱的抗抑郁样作用。药根碱（5、10和20 mg/kg，i. p.）或文拉法辛（20 mg/kg，i.g.）与赋形剂对照组相比，可显著减少不动持续时间。5.药根碱的浓度在脑组织中呈剂量依赖性增加。6.我们的研究表明药根碱可能通过抑制摄取-2转运蛋白而被用作抗抑郁药。
Abstract 1. Jatrorrhizine is an active ingredient found in various traditional Chinese medicinal plants. Based on our previous finding that jatrorrhizine was a potent inhibitor of OCT2 and OCT3, the aim of the present study was to explore whether jatrorrhizine has an antidepressant-like action action via inhibition of uptake-2 transporters. 2. In vitro uptake tests showed that jatrorrhizine strongly inhibited PMAT-mediated MPP+ uptake with an IC50 value of 1.05 μM and reduced 5-HT and NE uptake mediated by hOCT2, hOCT3 and hPMAT with IC50 values of 0.1–1 μM (for OCT2 and OCT3) and 1–10 μM (for PMAT). 3. In mouse synaptosomes, jatrorrhizine suppressed 5-HT and NE uptake in a concentration dependently manner, where the role of uptake-2 inhibition is significant. 4. The antidepressant-like action of jatrorrhizine was evaluated by mouse tail suspension test (TST). The TST showed that one week of jatrorrhizine (5, 10 and 20 mg/kg, i.p.) or venlafaxine (20 mg/kg, i.g.) can significantly reduce the duration of immobility when compared with vehicle control group. 5. The concentration of jatrorrhizine shows a dose-dependent increase in brain tissues. 6. Our study suggested that jatrorrhizine might be used as an antidepressant agent via inhibition of uptake-2 transporters.
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影响因子：
4.5
作者：
Mei-juan Tu;Siyuan Sun;Kai Wang;Xue-feng Peng;Ruihan Wang;Li-ping Li-Li-ping-Li-1651122038;S. Zeng;Hui Zhou;
通讯作者：
Mei-juan Tu;Siyuan Sun;Kai Wang;Xue-feng Peng;Ruihan Wang;Li-ping Li-Li-ping-Li-1651122038;S. Zeng;Hui Zhou;
影响因子：
4.7
作者：
Zhu HJ;Appel DI;Gründemann D;Markowitz JS
通讯作者：
Markowitz JS
DOI：
10.1093/oxfordhb/9780190634841.013.15
发表时间：
2018-11
期刊：
Oxford Handbooks Online
影响因子：
--
作者：
M. Lerner;Tamara E Rosen;Erin Kang;Cara M. Keifer;Alan H. Gerber
通讯作者：
M. Lerner;Tamara E Rosen;Erin Kang;Cara M. Keifer;Alan H. Gerber
影响因子：
3.3
作者：
Beibei Zhang;Aili Cao;Jiyan Zhou;Zhibi Hu;Dazheng Wu
通讯作者：
Beibei Zhang;Aili Cao;Jiyan Zhou;Zhibi Hu;Dazheng Wu
DOI：
--
发表时间：
1998-04
期刊：
The Journal of clinical psychiatry
影响因子：
--
作者：
D. Charney
通讯作者：
D. Charney