Abstract
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.
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Data Availability
Data will be made available on reasonable request.
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Acknowledgements
The authors are indebted to Modern Research Center for Traditional Chinese Medicine of Shanxi University for providing convenience in the experimental process. The authors are grateful to the editors and reviewers for their suggestions, which have greatly improved this paper.
Funding
This work was financially supported by the National S&T Major Projects for “Major New Drugs Innovation and Development” (No. 2017ZX09301047); the National Natural Science Foundation of China (No. 82074147 and No. 82374153); the Science and Technology of Shanxi Province (No. 202103021224026 and No. 202102130501010); the Young Talents from Huxiang (No. 2020RC3082).
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Jun-sheng Tian, Zhen-ning Wu, Dan Wu, Chen Yang, Yao Gao, Dong-lan Yan conceived and performed the experiments. Jun-sheng Tian and Zhen-ning Wu wrote the paper. Zhen-ning Wu, Dan Wu, Chen Yang, and Yao Gao contributed significantly to the manuscript preparation. Jun-sheng Tian and Xue-mei Qin got the project and designed the study. Jun-sheng Tian revised the manuscript and approved the final manuscript submitted. All the authors have read, revised, and approved the final version of the manuscript.
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The whole animal experiment was strictly in accordance with NIH Guide for the Care and Use of Laboratory Animals, maximum efforts were made to minimize animal suffering and the number of animals necessary for the capture of reliable data. The used animal protocol listed in the manuscript had been reviewed and approved by the Committee of Scientific Research in Shanxi University (CSRSX).
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Tian, Js., Wu, Zn., Wu, D. et al. Combining network pharmacology and experimental verification to reveal the mechanism of Chaigui granules in the treatment of depression through PI3K/Akt/mTOR signaling pathways. Metab Brain Dis 38, 2849–2864 (2023). https://doi.org/10.1007/s11011-023-01312-5
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DOI: https://doi.org/10.1007/s11011-023-01312-5