College of Pharmacy, Ningxia Medical University, Yinchuan, China.
Ningxia Research Center of Modern Hui Medicine Engineering and Technology, Ningxia Medical University, Yinchuan, China.
Phytother Res. 2020 Sep;34(9):2246-2257. doi: 10.1002/ptr.6675. Epub 2020 Apr 3.
SophoraflavanoneG (SG), an important prenylated flavonoid isolated from Sophoraalopecuroides.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.
槐黄酮 G（SG）是从苦参中分离得到的一种重要的苯丙素类黄酮，对多种疾病有效。本研究旨在探讨该化合物是否能逆转抑郁样症状，并探讨其可能的机制。慢性不可预测轻度应激（CUMS）小鼠用氟西汀和 SG 处理。记录强迫游泳试验（FST）和悬尾试验（TST）中的不动时间。评估海马体中促炎细胞因子和神经递质的水平。此外，还检测了海马体中 PI3K、AKT、mTOR、p70S6K、BDNF 和 Trkb 的蛋白表达。使用雷帕霉素（一种选择性 mTOR 抑制剂）来评估潜在的机制。结果表明，SG 治疗 7 天后，FST 和 TST 的不动时间明显减少。与 CUMS 暴露组相比，SG 处理组海马体中的 IL-6、IL-1β 和 TNF-α 水平显著降低，5-HT 和 NE 的含量明显升高。此外，SG 可以上调 PI3K、AKT、mTOR、70S6K、BDNF 和 Trkb 的表达。阻断哺乳动物雷帕霉素靶蛋白信号通路减弱了 SG 的抗抑郁作用，并逆转了 SG 引起的 BDNF 表达上调。这些发现表明，SG 通过 mTOR 介导的 BDNF/Trkb 信号通路治疗抑郁样症状。
