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阐明(Lim.)诱导松弛和抗抑郁的分子机制。

Elucidation of the Molecular Mechanism Underlying (Lim.)-Induced Relaxation and Anti-Depression.

机构信息

Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, 1-1-1 Tennodai, Tsukuba City 305-8572, Ibaraki, Japan.

Tsukuba Life Science Innovation Program (T-LSI), University of Tsukuba, Tennodai 1-1-1, Tsukuba City 305-8577, Ibaraki, Japan.

出版信息

Int J Mol Sci. 2019 Jul 20;20(14):3556. doi: 10.3390/ijms20143556.

Abstract

ethanolic extract (VEE) and verbascoside (Vs), a phenypropanoid glycoside, have been demonstrated to exert relaxant and anxiolytic properties. However, the molecular mechanisms behind their effects are still unclear. In this work, we studied the effects and action mechanisms of VEE and Vs and , on human neurotypic SH-SY5Y cells.TST was conducted on mice treated orally with VEE (25, 50 and 100 mg/Kg), Vs (2.5 and 5 mg/Kg), Bupropion (20 mg/Kg) and Milli-Q water. Higher dose of VEE-treated mice showed an increase of immobility time compared to control groups, indicating an induction of relaxation. This effect was found to be induced by regulation of genes playing key roles in calcium homeostasis (calcium channels), cyclic AMP (cAMP) production and energy metabolism. On the other hand, low doses of VEE and Vs showed an antidepressant-like effect and was confirmed by serotonin, noradrenalin, dopamine and BDNF expressions. Finally, VEE and Vsenhancedcell viability, mitochondrial activity and calcium uptake confirming findings. Our results showed induction of relaxation and antidepressant-like effects depending on the administered dose of VEE and Vs, through modulation of cAMP and calcium.

摘要

乙醇提取物(VEE)和苯丙素糖苷类化合物毛蕊花糖苷(Vs)已被证明具有松弛和抗焦虑作用。然而,其作用的分子机制仍不清楚。在这项工作中,我们研究了 VEE 和 Vs 对人神经典型 SH-SY5Y 细胞的作用和作用机制。TST 在口服给予 VEE(25、50 和 100mg/kg)、Vs(2.5 和 5mg/kg)、安非他酮(20mg/kg)和 Milli-Q 水的小鼠中进行。与对照组相比,高剂量 VEE 处理的小鼠表现出静止时间增加,表明诱导松弛。这种作用是通过调节在钙稳态(钙通道)、环磷酸腺苷(cAMP)产生和能量代谢中发挥关键作用的基因来诱导的。另一方面,低剂量的 VEE 和 Vs 表现出抗抑郁样作用,并通过 5-羟色胺、去甲肾上腺素、多巴胺和 BDNF 的表达得到证实。最后,VEE 和 Vs 增强了细胞活力、线粒体活性和钙摄取,证实了这一发现。我们的结果表明,VEE 和 Vs 的给药剂量依赖于诱导松弛和抗抑郁样作用,通过调节 cAMP 和钙。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb4c/6678442/2be0aeca6ef3/ijms-20-03556-g001.jpg

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