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植物源性黄酮黄芩素通过细胞外信号调节激酶级联反应发挥抗抑郁作用。

Antidepressant effects of a plant-derived flavonoid baicalein involving extracellular signal-regulated kinases cascade.

机构信息

Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

出版信息

Biol Pharm Bull. 2011;34(2):253-9. doi: 10.1248/bpb.34.253.

Abstract

Depression and related mood disorders are among the world's greatest public health problems. Previous studies have demonstrated that baicalein (Bai), one plant-derived active flavonoid, exhibits neuroprotection against ischemic brain injury and stimulates the levels of phosphorylation of extracellular signal-regulated kinase (pERK) and brain-derived neurotrophic factor (BDNF) expression in vivo. In this study, the antidepressant-like effects of baicalein was investigated using acute and chronic animal models of depression. The results showed that acute application of Bai at doses of 1, 2 and 4 mg/kg by intraperitoneal injection (i.p.) significantly reduced the immobility time in the forced swimming test (FST) and tail suspending test (TST) of mice. In addition, the chronic application of Bai by i.p. for 21 d also reduced the immobility time and improved locomotor activity in chronic unpredictable mild stress (CMS) model rats. Furthermore, it was shown that Bai reversed the reduction of extracellular ERKs phosphorylation and the level of BDNF expression in the hippocampus of CMS model rats. These results suggest that Bai produce an antidepressant-like effect and this effect is at least partly mediated by hippocampal ERK-mediated neurotrophic action.

摘要

抑郁症和相关的情绪障碍是世界上最大的公共卫生问题之一。先前的研究表明,黄芩素(Bai),一种植物来源的活性类黄酮,具有对抗缺血性脑损伤的神经保护作用,并能在体内刺激细胞外信号调节激酶(pERK)和脑源性神经营养因子(BDNF)表达的磷酸化水平。在这项研究中,使用急性和慢性抑郁动物模型研究了黄芩素的抗抑郁样作用。结果表明,腹腔注射(i.p.)1、2 和 4 mg/kg 的黄芩素急性给药显著减少了强迫游泳试验(FST)和悬尾试验(TST)中小鼠的不动时间。此外,腹腔注射 21 天的慢性给药也减少了慢性不可预测轻度应激(CMS)模型大鼠的不动时间和改善了运动活动。此外,研究表明,黄芩素逆转了 CMS 模型大鼠海马细胞外 ERK 磷酸化减少和 BDNF 表达水平降低的现象。这些结果表明,黄芩素产生抗抑郁样作用,这种作用至少部分是通过海马 ERK 介导的神经营养作用介导的。

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