Oh Hyeon-Muk, Lee Jin-Seok, Kim Seo-Woo, Oh Young-Taeck, Kim Won-Yong, Lee Sung-Bae, Cho Yong-Rae, Jeon Yoo-Jin, Cho Jung-Hyo, Son Chang-Gue
College of Korean Medicine, Daejeon University, Daejeon, South Korea.
Liver and Immunology Research Center, Daejeon Korean Medicine Hospital of Daejeon University, Daejeon, South Korea.
Front Pharmacol. 2020 Jan 31;10:1674. doi: 10.3389/fphar.2019.01674. eCollection 2019.
(UCW) is one of the most representative standardized herbal drugs for the treatment of central nervous system diseases, including mood disorders, and has been used for over 600 years in Korea and China. In spite of the long clinical application of UCW, no experimental evidence for its use against depressive disorders exists. Here, we performed an animal study to investigate the anti-depressive effect of UCW and the underlying mechanisms.
A social isolation-induced depressive-like model was produced using C57BL/6J male mice by housing the mice individually for 31 days, and the mice underwent daily oral administration of distilled water, UCW (100, 200, 400 mg/kg) or fluoxetine (20 mg/kg) during the final 17 days. A tail suspension test (TST), forced swimming test (FST), and open field test (OFT) were used to explore the effects of UCW on depressive-like behaviors. 5-Hydroxytryptamine (5-HT) was measured in the dorsal raphe nuclei (DRN) using immunofluorescence. The serum corticosterone level was measured with its receptor and catecholamine, along with cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the hippocampus.
Social isolation stress effectively induced depressive-like behaviors, and UCW treatment significantly improved the symptoms of depressive-like behavior in the FST, TST, and OFT. The isolation stress-induced depletion of 5-HT was significantly ameliorated by UCW treatment. UCW also attenuated the activation of the glucocorticoid receptor (GR) and the elevated serum corticosterone level, as well as the hippocampal levels of dopamine and norepinephrine. Dexametasone-derived translocation of GR was inhibited by UCW treatment in PC12 cells and HT22 cells. In addition, alterations of tryptophan hydroxylase 2 (TPH2), BDNF, and CREB in the protein analyses were notably regulated by UCW treatment.
These results provide animal-based evidence for the anti-depressive effect of UCW, and its underlying mechanisms may involve regulating the serotonergic system, the hypothalamic-pituitary-adrenal (HPA) axis, and neurotrophin.
（某草药复方，此处用英文缩写 UCW 指代）是治疗中枢神经系统疾病（包括情绪障碍）最具代表性的标准化草药之一，在韩国和中国已使用了 600 多年。尽管 UCW 临床应用历史悠久，但尚无其治疗抑郁症的实验证据。在此，我们进行了一项动物研究，以探究 UCW 的抗抑郁作用及其潜在机制。
使用 C57BL/6J 雄性小鼠，通过单独饲养 31 天建立社会隔离诱导的抑郁样模型，在最后 17 天，小鼠每天口服蒸馏水、UCW（100、200、400mg/kg）或氟西汀（20mg/kg）。采用悬尾试验（TST）、强迫游泳试验（FST）和旷场试验（OFT）来探究 UCW 对抑郁样行为的影响。使用免疫荧光法测量中缝背核（DRN）中的 5-羟色胺（5-HT）。测量血清皮质酮水平及其受体、儿茶酚胺，以及海马体中的环磷酸腺苷反应元件结合蛋白（CREB）和脑源性神经营养因子（BDNF）。
社会隔离应激有效诱导了抑郁样行为，UCW 治疗显著改善了 FST、TST 和 OFT 中的抑郁样行为症状。UCW 治疗显著改善了隔离应激诱导的 5-HT 耗竭。UCW 还减弱了糖皮质激素受体（GR）的激活、血清皮质酮水平的升高，以及海马体中多巴胺和去甲肾上腺素的水平。在 PC12 细胞和 HT22 细胞中，UCW 治疗抑制了地塞米松诱导的 GR 易位。此外，UCW 治疗显著调节了蛋白质分析中色氨酸羟化酶 2（TPH2）、BDNF 和 CREB 的变化。
这些结果为 UCW 的抗抑郁作用提供了基于动物的证据，其潜在机制可能涉及调节血清素能系统、下丘脑-垂体-肾上腺（HPA）轴和神经营养因子。
