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首页> 外文期刊>RSC Advances >A urinary metabolomics (GC-MS) strategy to evaluate the antidepressant-like effect of chlorogenic acid in adrenocorticotropic hormone-treated rats
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A urinary metabolomics (GC-MS) strategy to evaluate the antidepressant-like effect of chlorogenic acid in adrenocorticotropic hormone-treated rats

机译：尿代谢物（GC-MS）策略评价肾上腺激素治疗大鼠肾上腺素的抗抑郁药物

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摘要

Major depressive disorder (MDD) is a chronic recurring illness that seriously affects human health. Chlorogenic acid (CGA), an important polyphenol extracted from Eucommia ulmoides Oliver bark, has been reported to have anti-depression, neuroprotection, memory improvement and other pharmacological effects. However, little is known about the underlying mechanisms of CGA on the treatment of depression. Here, we investigated the antidepressant-like effects of CGA on an adrenocorticotropic hormone (ACTH)-treated rat model. Thirty-two male Wistar rats were randomly divided into four groups: normal diet group (N), ACTH-treated model group (M), memantine positive control group (M + Mem) and CGA intervened group (M + CGA). Sucrose preference tests (SPTs) and open-field tests (OFTs) were performed to evaluate depressive-like behaviors. Memantine (30 mg kg(-1)) and CGA (500 mg kg(-1)) administration dramatically increased hedonic behaviors of the rats in SPT. The scores of crossing and rearing were significantly increased in the M + Mem group and M + CGA group. These results of the behaviour tests might be suggestive of antidepressant-like effects. Moreover, memantine and CGA reversed the levels of serum 5-hydroxytryptamine (5-HT), ACTH, corticotropin-releasing hormone (CRH), and dopamine (DA) that were altered in ACTH-treated rats. Based on a GC-MS metabolomic approach, significant differences in the metabolic profile were observed in ACTH-treated rats compared with the control group, as well as the M + CGA group and M + Mem group compared with the ACTH-treated group. A total of 19 metabolites were identified for the discrimination of normal rats and ACTH-treated rats, and 12 out of 19 differential metabolites were reversed with CGA intervention. Combined with pattern recognition and bioinformatics, nine perturbed metabolic pathways, including energy metabolism, neurotransmitter metabolism, and amino acid metabolism, were identified based on these metabolites. These integrative studies might give a holistic insight into the pathophysiological mechanism of the ACTH-treated depressive rat model, and also showed that CGA has antidepressant-like activities in ACTH-treated rats, providing an important drug candidate for the prevention and treatment of tricyclic anti-depressant treatment-resistant depression.
机译：主要抑郁症（MDD）是一种严重影响人类健康的慢性经常性疾病。据报道，从杜仲ouropia ofliver oliver oilliver oilliver oilliver oilliver oilliver oilliver oilliver oilliver oiliver aliver（cga）具有抗抑郁，神经保护，记忆力和其他药理作用。然而，对CGA的潜在机制毫无熟悉抑郁症治疗的潜在机制。在这里，我们研究了CGA对肾上腺皮质激素（ACTH）-TREATED大鼠模型的抗抑郁药物。将32只雄性Wistar大鼠随机分为四组：正常饮食组（N），ACTH处理的模型组（M），Memantine阳性对照组（M + MEM）和CGA介入基团（M + CGA）。进行蔗糖偏好测试（SPTS）和开放场测试（OFTS）以评估抑郁状行为。 Memantine（30mg kg（-1））和Cga（500mg kg（-1））施用在SPT中大大增加了大鼠的蜂窝的行为。在M + MEM组和M + CGA组中，交叉和饲养的得分显着增加。行为测试的这些结果可能提示抗抑郁药物的效果。此外，Memantine和CGA逆转了在ActH处理的大鼠中改变的血清5-羟基 - 羟基胺（5-HT），ACTH，皮质大鼠释放激素（CRH）和多巴胺（DA）的水平。基于GC-MS代谢物方法，与对照组比较的大鼠和M + CGA组和M + MEM组在actH处理的大鼠中观察到代谢曲线的显着差异，与ACTH处理基团相比。鉴定了总共19种代谢物，用于判断正常大鼠和acth处理的大鼠，并且通过CGA干预逆转了19种差分代谢物中的12种。结合模式识别和生物信息学，基于这些代谢物鉴定了九种扰动代谢途径，包括能量代谢，神经递质代谢和氨基酸代谢。这些综合研究可能会对acth治疗的抑郁大鼠模型的病理生理机制提供全面的洞察力，并且还表明CGA在抗抗癌症治疗的大鼠中具有抗抑郁药物的活性，为预防和治疗三环抗体提供了重要的药物候选者。 - 抑制治疗耐药抑郁症。

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  • 来源
    《RSC Advances》 |2018年第17期|共11页
  • 作者

    Zhao Le; Zhang Zixu; Zhou Mingmei; Gou Xiaojun; Zeng Yang; Song Jing; Ma Weini; Xu Ying;

  • 作者单位

    Shanghai Univ Tradit Chinese Med Ctr Chinese Med Therapy &

    Syst Biol 1200 Cailun Rd Shanghai 201203 Peoples R China;

    Shanghai Univ Tradit Chinese Med Ctr Chinese Med Therapy &

    Syst Biol 1200 Cailun Rd Shanghai 201203 Peoples R China;

    Shanghai Univ Tradit Chinese Med Ctr Chinese Med Therapy &

    Syst Biol 1200 Cailun Rd Shanghai 201203 Peoples R China;

    Shanghai Univ Tradit Chinese Med Baoshan Dist Hosp Integrated Tradit Chinese &

    Wes Cent Lab Shanghai 201999 Peoples R China;

    Qinghai Normal Univ Coll Life Sci Xining 810008 Qinghai Peoples R China;

    Shanghai Univ Tradit Chinese Med Ctr Chinese Med Therapy &

    Syst Biol 1200 Cailun Rd Shanghai 201203 Peoples R China;

    Shanghai Univ Tradit Chinese Med Ctr Chinese Med Therapy &

    Syst Biol 1200 Cailun Rd Shanghai 201203 Peoples R China;

    Shanghai Univ Tradit Chinese Med Dept Physiol Shanghai 201203 Peoples R China;

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