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Depression is a commonly occurring neuropsychiatric disease with an increasing incidence rate. Saikosaponin A (SA), a major bioactive component extracted from Radix Bupleuri, possesses anti-malignant cell proliferation, anti-inflammation, anti-oxidation and liver protective effects. However, few studies have investigated SA's antidepressant effects and pharmacological mechanisms of action. Our study aimed to explore the anti-depression effect of SA and screen the target proteins regulated by SA in a rat model of chronic unpredictable mild stress (CUMS)-induced depression. Results showed that 8-week CUMS combined with separation could successfully produce depressive-like behaviours and cause a decrease of dopamine (DA) in rat hippocampus, and 4-week administration of SA could relieve CUMS rats' depressive symptoms and up-regulated DA content. There were 15 kinds of significant differentially expressed proteins that were detected not only between the control and CUMS groups, but also between the CUMS and SA treatment groups. Proline-rich transmembrane protein 2 (PRRT2) was down-regulated by CUMS while up-regulated by SA. These findings reveal that SA may exert antidepressant effects by up-regulating the expression level of PRRT2 and increasing DA content in hippocampus. The identification of these 15 differentially expressed proteins, including PRRT2, provides further insight into the treatment mechanism of SA for depression. © 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Citation

Juanjuan Guo, Feng Zhang, Jifang Gao, Xinyuan Guan, Beiyun Liu, Xiaoge Wang, Zhaoyu Qin, Kuanxiao Tang, Shilian Liu. Proteomics-based screening of the target proteins associated with antidepressant-like effect and mechanism of Saikosaponin A. Journal of cellular and molecular medicine. 2020 Jan;24(1):174-188

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PMID: 31762213

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