Introduction

Chaigui granules are a novel manufactured traditional Chinese antidepressant medicine, which is originated from the ancient classical prescription of Xiaoyaosan. It ameliorated depression-like behavior and concomitant symptoms in animal models. But its antidepressant mechanism is still unclear. Therefore, network pharmacology and molecular biology were used to explore underlying antidepressant mechanism in this study.

Methods

Firstly, network pharmacology was used to screen main active ingredients and potential targets in the treatment of depression with Chaigui granules, and to perform pathway enrichment analysis. Secondly, chronic and unpredictable mild stress-induced depression model rats were used, and behavioral tests were used to evaluate the antidepressant effect of Chaigui granules. Finally, the core targets and key pathways predicted by network pharmacology were validated by qRT-PCR and Western blot to determine the relevant gene and protein expression levels in rat hippocampus.

Results

The results of network pharmacology indicated that the PI3K/Akt signaling pathway may play a key role in antidepressant of Chaigui granules. The results of animal experiments showed that Chaigui granules significantly modulated behavioral indicators. Subsequently, the upregulation of relative mRNA levels of mTOR, Akt and PI3K and downregulation of GSK-3β and FoxO3a were observed in rat hippocampus by molecular biology diagnosis. In addition, the decreased expression of Akt and mTOR in CUMS rats hippocampus was significantly reversed, and the expression levels of GSK-3β and FoxO3a were upregulated.

Conclusions

Based on the results of network pharmacology and animal experiment validation, Chaigui granules may reverse CUMS-induced depression-like behavior in rats through PI3K/Akt/mTOR signaling pathway.

中文翻译：

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结合网络药理学和实验验证揭示柴桂颗粒通过PI3K/Akt/mTOR信号通路治疗抑郁症的作用机制

介绍

柴桂颗粒是一种新型中药抗抑郁药，源自古代经典方逍遥散。它改善了动物模型中的抑郁样行为和伴随症状。但其抗抑郁机制仍不清楚。因此，本研究利用网络药理学和分子生物学来探讨潜在的抗抑郁机制。

方法

首先利用网络药理学筛选柴桂颗粒治疗抑郁症的主要活性成分和潜在靶点，并进行通路富集分析。其次，采用慢性、不可预测的轻度应激性抑郁模型大鼠，通过行为学试验评价柴桂颗粒的抗抑郁作用。最后，通过qRT-PCR和Western blot验证网络药理学预测的核心靶点和关键通路，以确定大鼠海马中相关基因和蛋白的表达水平。

结果

网络药理学结果表明PI3K/Akt信号通路可能在柴桂颗粒的抗抑郁作用中发挥关键作用。动物实验结果表明，柴桂颗粒对行为指标具有显着调节作用。随后，通过分子生物学诊断，观察到大鼠海马mTOR、Akt和PI3K mRNA相对水平上调，GSK-3β和FoxO3a相对下调。此外，CUMS大鼠海马中Akt和mTOR下降的表达显着逆转，GSK-3β和FoxO3a的表达水平上调。

结论

根据网络药理学和动物实验验证结果，柴桂颗粒可能通过PI3K/Akt/mTOR信号通路逆转CUMS诱导的大鼠抑郁样行为。