越鞠甘麦大枣汤具有快速抗抑郁样作用及抑制 NMDA/NO/cGMP 信号通路的参与。
Yueju-Ganmaidazao Decoction confers rapid antidepressant-like effects and the involvement of suppression of NMDA/NO/cGMP signaling.
机构信息
Key Laboratory of Integrative Biomedicine for Brain Diseases, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, 226001, China.
Key Laboratory of Integrative Biomedicine for Brain Diseases, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
出版信息
J Ethnopharmacol. 2020 Mar 25;250:112380. doi: 10.1016/j.jep.2019.112380. Epub 2019 Nov 7.
ETHNOPHARMACOLOGICAL RELEVANCE
Yueju-Ganmaidazao Decoction (YG) is a multiherbal medicine prescribed for treatment of mood disorder, consisting of two classical traditional Chinese herbal medicine Yueju and Ganmaidazao. Yueju and Ganmaidazao both are used for depression treatment. The combined decoction of Yueju and Ganmaidazao is prescribed to achieve optimal clinical outcomes by dealing with different symptoms of depression. Recent studies indicated ethanol extract of Yueju was capable to confer rapid antidepressant-like response. The antidepressant activity of YG decoction with fast-onset feature remains to be investigated.
AIM OF THE STUDY
Rapid and safe antidepressant treatment is urgently needed. This study aimed to assess the rapid antidepressant-like activity of YG and the underlying mechanism, focusing on NMDA/NO/cGMP signaling.
MATERIALS AND METHODS
The optimal doses for immediate and persistent antidepressant-like response were first screened using tail suspension test (TST) and forced swimming test (FST) post a single administration of YG. The rapid action was further confirmed by using the chronic mild stress (CMS) and learned helplessness (LH) paradigms. The expressions of NMDA receptor subunits were evaluated post stress and YG. The contributions of NMDA, NO, and cGMP signaling to the antidepressant effect of YG were investigated systematically using pharmacological interventions.
RESULTS
The optimal dose for immediate and persistent antidepressant potential, evidenced with reduced immobility times in TST or FST from 30 min to 7 days, was determined. The rapid antidepressant-like effect was confirmed in CMS and LH paradigms, including instant normalization of sucrose preference behavior. The expression of NMDA subunit NR1 in the hippocampus was reduced from 30 min to 5 days post YG. In animals subjected to CMS and LH, hippocampal NR1 expression increased, reversed by YG. YG's antidepressant-like effect was blunted by pretreatment with the agonists along the signalings including NMDA (75 mg/kg), L-arginine (750 mg/kg) and sildenafil (5 mg/kg) in TST or FST. Conversely, administration of subeffective dose of individual antagonists, including MK-801 (0.05 mg/kg), 7-nitroindazole (30 mg/kg), methylene blue (10 mg/kg), in combination with a subeffective dose of YG, elicited antidepressant effects.
CONCLUSION
YG conferred rapid antidepressant-like effects, and the antidepressant response was essentially dependent on suppression of NMDA/NO/cGMP signaling.
民族药理学相关性
越鞠甘麦大枣汤（YG）是一种多草药药物，用于治疗情绪障碍，由两种经典的中药越鞠和甘麦大枣组成。越鞠和甘麦大枣都用于治疗抑郁症。越鞠和甘麦大枣的联合汤被开处方以通过处理抑郁症的不同症状来达到最佳的临床效果。最近的研究表明，越鞠的乙醇提取物能够赋予快速抗抑郁样反应。YG 汤具有快速发作特征的抗抑郁活性仍有待研究。
研究目的
快速和安全的抗抑郁治疗是急需的。本研究旨在评估 YG 的快速抗抑郁样活性及其潜在机制，重点关注 NMDA/NO/cGMP 信号。
材料和方法
首先使用尾部悬挂试验（TST）和强迫游泳试验（FST）筛选单次给药 YG 后具有即时和持久抗抑郁样反应的最佳剂量。通过慢性轻度应激（CMS）和习得性无助（LH）模型进一步确认快速作用。应激后和 YG 后评估 NMDA 受体亚基的表达。系统地使用药理学干预研究 NMDA、NO 和 cGMP 信号对 YG 抗抑郁作用的贡献。
结果
确定了具有即时和持久抗抑郁潜力的最佳剂量，表现在 TST 或 FST 中的不动时间从 30 分钟减少到 7 天。在 CMS 和 LH 模型中证实了快速抗抑郁样作用，包括即时正常化蔗糖偏好行为。YG 后 30 分钟至 5 天，海马 NMDA 亚基 NR1 的表达减少。在 CMS 和 LH 处理的动物中，海马 NR1 的表达增加，被 YG 逆转。在 TST 或 FST 中，用激动剂预处理会减弱 YG 的抗抑郁样作用，包括 NMDA（75mg/kg）、L-精氨酸（750mg/kg）和西地那非（5mg/kg）。相反，给予亚有效剂量的单个拮抗剂，包括 MK-801（0.05mg/kg）、7-硝基吲唑（30mg/kg）、亚甲蓝（10mg/kg），与亚有效剂量的 YG 联合使用，会产生抗抑郁作用。
结论
YG 赋予快速抗抑郁样作用，抗抑郁反应本质上依赖于抑制 NMDA/NO/cGMP 信号。
Zotero 插件