Xiao Yao San Improves Depressive-Like Behavior in Rats through Modulation of β-Arrestin 2-Mediated Pathways in Hippocampus.

Xiao Yao San Improves Depressive-Like Behavior in Rats through Modulation of β-Arrestin 2-Mediated Pathways in Hippocampus.
复制标题

逍遥散通过调节海马β-抑制蛋白2介导的通路改善大鼠抑郁样行为

DOI:
10.1155/2014/902516
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发表时间:
2014
期刊:
Evidence-based complementary and alternative medicine : eCAM
影响因子:
--
通讯作者:
Sun X
Sun X
中科院分区:
其他
文献类型:
--
作者:
Zhu X;Xia O;Han W;Shao M;Jing L;Fan Q;Liu Y;Diao J;Lv Z;Sun X

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逍遥散(XYS)是一种经典的中药配方,数百年来一直被广泛用于治疗情绪障碍。为了证实XYS的作用并更好地了解其作用机制,我们对社会隔离和慢性不可预知轻度应激(CUMS-)治疗的大鼠进行了基于高效液相色谱-质谱分析的XYS提取物质量控制和基于蛋白质组学的海马差异蛋白鉴定。CUMS诱导大鼠的抑郁样行为与人类抑郁的表现相似。皮质酮(CORT)和尿皮质素2 (UCN2)水平上调表明存在下丘脑-垂体-肾上腺(HPA)轴亢进。XYS可有效改善抑郁样行为,下调UCN2和CORT。XYS降低了丝氨酸/苏氨酸蛋白磷酸酶2A亚基B的表达,增加了β-阻滞蛋白2的表达。脑源性神经营养因子(BDNF)、酪氨酸受体激酶B (TrkB)和哺乳动物雷帕霉素靶蛋白(mTOR)的表达也升高。综上所述,XYS通过下调促肾上腺皮质激素释放激素(CRH)受体2来改善社会隔离和cms诱导的抑郁样行为,并改善HPA过度激活。BDNF/TrkB的上调和mTOR的磷酸化需要β-阻滞蛋白2作为支架来调节应激信号。
Xiao Yao San (XYS) is a classical Chinese medicine formula that has been widely used to treat mood disorders for hundreds of years. To confirm the effect of XYS and better understand its underlying mechanism, high-performance liquid chromatography-mass spectrometry analysis-based quality control of XYS extracts and proteomics-based identification of differential proteins in the hippocampus were adopted in social isolation and chronic unpredictable mild stress- (CUMS-) treated rats. The depressive-like behavior of rats induced by CUMS resembled the manifestation of human depression. The upregulated corticosterone (CORT) and urocortin 2 (UCN2) levels demonstrated the existence of hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. XYS was effective in ameliorating the depressive-like behavior and downregulating UCN2 and CORT. XYS decreased the expression of serine/threonine-protein phosphatase 2A subunit B and increased the expression of β-arrestin 2. The expressions of brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB), and mammalian target of rapamycin (mTOR) were also elevated by XYS. In conclusion, XYS improves social isolation and CUMS-induced depressive-like behavior and ameliorates HPA hyperactivation through the downregulation of corticotrophin releasing hormone (CRH) receptor 2. The upregulation of BDNF/TrkB and the phosphorylation of mTOR require β-arrestin 2 as a scaffold to regulate stress signaling.
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