KeYu ShuShen Granule alleviates symptoms of depression by targeting the mTOR pathway in a rat model of depression induced by chronic unpredictable mild stress

Abstract

Background

KeYu ShuoShen Granules (KSG) is a traditional Chinese medicine formula with radix bupleuri as the kingpin, which is widely used in the treatment of depression, but its exact mechanism of action is not yet fully understood. The aim of this study is to investigate the therapeutic mechanisms of KSG in a model of depression in rats.

Methods

Rats were equally divided into 5 groups including control, model, fluoxetine, KSG at high and low doses, chronic unpredictable mild stress combined with solitary rearing for 28 days was used to prepare a rat model of depression followed by 14 days of continuous gavage and modelling, and the antidepressant effects of KSG were analyzed using behavioral tests, proteomic techniques and pharmacological methods.

Results

After KGS treatment, the body weight, Sucrose Preference of the model rats increased significantly, and their motor and learning memory abilities were significantly improved in the open field test and Morris water maze (P<0.01 or P<0.05); At the same time, proteomics revealed a total of 7 differential proteins, 3 differential pathways, including Agps, Eif4e2, Pter, Sys1, Rgcc, Polr1d and Npy1r, mTOR signalling pathway, insulin signalling pathway, and human papillomavirus infection; the expression of p-mTOR, mTOR, and Eif4e2 was significantly up-regulated after drug administration (P<0.01 or P<0.05), and neuronal damage in the cerebral cortex was significantly restored.

Conclusion

KSG improved depression symptoms in model rats by modulating protein synthesis processes involved in the mTOR pathway and Eif4e2, producing a combined effect on the nervous system. This finding provides new theoretical support and a mechanistic explanation for the use of KSG in the treatment of depression.