Involvement of mTOR-related signaling in antidepressant effects of Sophoraflavanone G on chronically stressed mice
Involvement of mTOR-related signaling in antidepressant effects of Sophoraflavanone G on chronically stressed mice
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mTOR 相关信号传导参与槐黄酮 G 对慢性应激小鼠的抗抑郁作用
DOI：
10.1002/ptr.6675
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发表时间：
2020
影响因子：
7.2
通讯作者：
Xia Baomei
中科院分区：
文献类型：
--
作者：
Wang Hanqing;Tong Yue;Xiao Dong;Xia Baomei
SophoraflavanoneG (SG) 是从槐花槐中分离出来的一种重要的异戊二烯化黄酮类化合物，对多种疾病有效。本研究旨在调查该化合物是否可以逆转抑郁样症状并探讨其可能的机制。慢性不可预测轻度应激 (CUMS) 小鼠接受氟西汀和 SG 治疗。记录强迫游泳试验（FST）和悬尾试验（TST）中的不动时间。评估海马中促炎细胞因子和神经递质的水平。检测海马PI3K、AKT、mTOR、p70S6K、BDNF、Trkb蛋白表达量。雷帕霉素（Rapamycin），一种选择性 mTOR 抑制剂，被用来评估潜在的机制。结果，SG治疗7天后，FST和TST的不动时间明显下降。与 CUMS 暴露组相比，SG 治疗组海马 IL-6、IL-1β 和 TNF-α 水平显着降低，5-HT 和 NE 数量显着升高。此外，SG 可以上调 PI3K、AKT、mTOR、70S6K、BDNF 和 Trkb 的表达。哺乳动物雷帕霉素信号传导靶标的阻断减弱了抗抑郁作用，并逆转了 SG 引起的 BDNF 表达上调。这些发现表明 SG 治疗通过 mTOR 介导的 BDNF/Trkb 信号缓解抑郁样症状。
SophoraflavanoneG (SG), an important prenylated flavonoid isolated fromSophoraalopecuroides.L, is effective for many illnesses. The present study was designed to investigate whether the compound could reverse depressive‐like symptoms and investigate its possible mechanisms. Chronic Unpredictable Mild Stress (CUMS) mice were treated with fluoxetine and SG. The immobility time in forced swimming test (FST) and tail suspension test (TST) were recorded. The levels of pro‐inflammatory cytokines and neurotransmitters in the hippocampus were evaluated. Furthermore, the protein expressions of PI3K, AKT, mTOR, p70S6K, BDNF, and Trkb in hippocampus were detected. Rapamycin, the selective mTOR inhibitor, was used to estimate the potential mechanism. As a result, after 7 days of SG treatment, the immobility time in FST and TST was declined obviously. The levels of IL‐6, IL‐1β, and TNF‐α in the hippocampus were significantly reduced, and the quantity of 5‐HT and NE was raised considerably in SG‐treated group compared with the CUMS‐exposed group. Additionally, SG could up‐regulate the expressions of PI3K, AKT, mTOR, 70S6K, BDNF, and Trkb. The blockade of mammalian target of rapamycin signaling blunted the antidepressant effect and reversed the up‐regulation of BDNF expression caused by SG. These findings suggested that SG treatment alleviated depressive‐like symptoms via mTOR‐mediated BDNF/Trkb signaling.