Mizuki Daishu, Matsumoto Kinzo, Tanaka Ken, Thi Le Xoan, Fujiwara Hironori, Ishikawa Tsutomu, Higuchi Yoshihiro
Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan.
Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan.
J Ethnopharmacol. 2014 Oct 28;156:16-25. doi: 10.1016/j.jep.2014.08.014. Epub 2014 Aug 23.
Butea superba (BS) is a Thai medicinal plant that has been used as a folk medicine to improve physical and mental conditions and to prevent impaired sexual performance in middle-aged or elderly males. We have previously reported that this plant extract could improve cognitive deficits and depression-like behavior in olfactory bulbectomized mice, an animal model of dementia and depression.
In this study we examined the effect of BS on depression-like behavior in mice subjected to unpredictable chronic mild stress (UCMS) to clarify the antidepressant-like activity of BS and the molecular mechanism underlying this effect.
UCMS mice were administered BS daily (300 mg of dried herb weight/kg, p.o.) or a reference drug, imipramine (IMP, 10 mg/kg, i.p.), 1 week after starting the UCMS procedure. We employed the sucrose preference test and the tail suspension test to analyze anhedonia and depression-like behavior of mice, respectively. Serum and brain tissues of mice were used for neurochemical and immunohistochemical studies. The UCMS procedure induced anhedonia and depression-like behavior, and BS treatment, as well as IMP treatment, attenuated these symptoms. UCMS caused an elevation of serum corticosterone level, an index of hyper-activation of the hypothalamic-pituitary-adrenal (HPA) axis, in a manner attenuated by BS and IMP treatment. BS treatment also attenuated UCMS-induced decrease in the expression levels of brain-derived neurotrophic factor (BDNF) mRNA, cyclic AMP-responsive element binding protein (CREB) and a phosphorylated form of N-methyl-d-aspartate receptor subunit NR1, synaptic plasticity-related signaling proteins. Moreover, the UCMS procedure reduced doublecortin-positive cells in the dentate gyrus region of the hippocampus. BS administration reversed these UCMS-induced neurochemical and histological abnormalities.
These results suggest that BS can ameliorate chronic stress-induced depression-like symptoms and that the effects of BS are mediated by restoring dysfunctions of the HPA axis and synaptic plasticity-related signaling systems and neurogenesis in the hippocampus.
艳紫铆是一种泰国药用植物，一直被用作民间药物，用于改善中老年人的身心状况以及预防性功能障碍。我们之前报道过，这种植物提取物可以改善嗅球切除小鼠的认知缺陷和抑郁样行为，嗅球切除小鼠是痴呆和抑郁的动物模型。
在本研究中，我们检测了艳紫铆对经历不可预测的慢性轻度应激（UCMS）小鼠抑郁样行为的影响，以阐明艳紫铆的抗抑郁样活性及其作用的分子机制。
在开始UCMS程序1周后，每天给UCMS小鼠灌胃艳紫铆（300mg干草药重量/千克，口服）或参比药物丙咪嗪（IMP，10mg/千克，腹腔注射）。我们分别采用蔗糖偏好试验和悬尾试验分析小鼠的快感缺失和抑郁样行为。小鼠的血清和脑组织用于神经化学和免疫组织化学研究。UCMS程序诱发了快感缺失和抑郁样行为，艳紫铆治疗以及IMP治疗均减轻了这些症状。UCMS导致血清皮质酮水平升高，这是下丘脑-垂体-肾上腺（HPA）轴过度激活的指标，而艳紫铆和IMP治疗可减轻这种升高。艳紫铆治疗还减轻了UCMS诱导的脑源性神经营养因子（BDNF）mRNA、环磷腺苷反应元件结合蛋白（CREB）以及N-甲基-D-天冬氨酸受体亚基NR1的磷酸化形式（突触可塑性相关信号蛋白）表达水平的降低。此外，UCMS程序减少了海马齿状回区域双皮质素阳性细胞的数量。给予艳紫铆可逆转这些由UCMS诱导的神经化学和组织学异常。
这些结果表明，艳紫铆可以改善慢性应激诱导的抑郁样症状，其作用是通过恢复HPA轴功能障碍、突触可塑性相关信号系统以及海马神经发生来介导的。
