Saikosaponin A attenuates perimenopausal depression-like symptoms by chronic unpredictable mild stress

Saikosaponin A attenuates perimenopausal depression-like symptoms by chronic unpredictable mild stress
复制标题

柴胡皂苷 A 通过慢性不可预测的温和压力减轻围绝经期抑郁症样症状

DOI:
10.1016/j.neulet.2017.09.046
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发表时间:
2018-01-01
影响因子:
2.5
通讯作者:
Li, Can-Dong
Li, Can-Dong
中科院分区:
医学4区
文献类型:
--
作者:
Chen, Xue-Qin;Chen, Shu-Jiao;Li, Can-Dong

文献摘要

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近年来的大量研究表明,柴胡疏肝散具有抗啮齿类动物包括围绝经期类动物的类风湿性关节炎的作用。以往的研究和我们的初步研究表明柴胡疏肝散的主要成分之一柴胡皂苷A能增强大鼠脑源性神经营养因子(BDNF)的表达。在此,本研究旨在评估柴胡皂苷A的抗抑郁样作用在围绝经期大鼠暴露于慢性不可预测的轻度应激(CIMIS)。给药4周后进行蔗糖偏好试验、新奇性抑制摄食试验和强迫游泳试验。测定血清促肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)和皮质酮水平,以及下丘脑CRH和海马糖皮质激素受体。此外,检测海马中的促炎细胞因子如白细胞介素-1 β(IL-β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)以评价神经炎症。此外,还测定了BDNF水平及其受体TrkB。我们的研究结果表明,4周的治疗柴胡皂甙A增加蔗糖偏好,减少潜伏期喂养的新奇抑制喂养试验和减少不动时间在强迫游泳试验。此外,柴胡皂苷A还能恢复HPS大鼠HPA轴的失调和神经炎症。此外,柴胡皂苷A促进海马中的BDNF-TrkB信号传导。本研究表明,柴胡皂苷A在大鼠中产生抗癫痫样作用,这可能是通过恢复围绝经期海马神经内分泌、神经炎症和神经营养系统介导的。
Accumulating studies have shown that a traditional Chinese decoction Chaihu-Shugan-San produced the anti-depressant-like effects in rodents including in perimenopausal. Previous studies and our preliminary study indicated that saikosaponin A, one of the main constituents of Chaihu-Shugan-San, enhanced brain-derived neurotrophic factor (BDNF) expression in rats. Herein, this study aimed to evaluate the antidepressant-like effects of saikosaponin A in perimenopausal rats exposed to chronic unpredictable mild stress (CUMS). The sucrose preference test, novelty-suppressed feeding test and forced swimming test were performed after administration of saikosaponin A for 4 weeks. Serum corticotrophin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone levels, as well as hypothalamus CRH and hippocampal glucocorticoid receptor were measured. In addition, pro-inflammatory cytokines such as interleukin-1beta (IL-beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in the hippocampus were detected for evaluation of the neuroinflammation. Further, BDNF levels and its receptor TrkB were also determined. Our results indicated that four-week treatment with saikosaponin A increased sucrose preference, decreased latency to feed in the novelty-suppressed feeding test and reduced the immobility time in the forced swimming test. In addition, saikosaponin A restored the dsyregulation of HPA axis and neuroinflammation in rats exposed to CUMS. Moreover, saikosaponin A promoted BDNF-TrkB signaling in the hippocampus. This study demonstrates that saikosaponin A produced the anti-depressant-like effects in rats, which may be mediated by restoration of neuroendocrine, neuroinflammation and neurotrophic systems in the hippocampus during perimenopausal.