Chaihu-Shugan-San inhibits neuroinflammation in the treatment of post-stroke depression through the JAK/STAT3-GSK3β/PTEN/Akt pathway

Fan Q, Liu Y, Sheng L, Lv S, Yang L, Zhang Z, Guo J, Fan Y, Hu D · Biomedicine & Pharmacotherapy · 2023 April

DOI 10.1016/j.biopha.2023.114385

Objective

To investigate whether Chaihu-Shugan-San improves post-stroke depression symptoms in a rat model, to explore the underlying mechanisms, and to validate the findings in an in vitro oxygen and glucose deprivation model.

Conclusions

Chaihu-Shugan-San has therapeutic effects in models of post-stroke depression and regulates microglial polarization through activation of the Janus kinase/signal transducer and activator of transcription 3-glycogen synthase kinase 3 beta-phosphatase and tensin homolog/protein kinase B pathway, thereby inhibiting neuroinflammation.

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Insights

Chaihu-Shugan-San, a traditional Chinese medicine, can improve symptoms in a post-stroke depression rat model by regulating microglia polarization, thereby inhibiting neuroinflammation.

The study utilized male rats which were subjected to conditions simulating the effects of stroke and chronic unpredictable mild stress. Rats were then separated into groups that received various treatments including Chaihu-Shugan-San, a JAK-STAT3 inhibitor, a GSK3β overexpressing virus, or an empty virus (control). Alongside these groups were rats that received no specific treatment and rats not exposed to the initial stroke/chronic stress situation. All treated rats then underwent a series of tests, which included forced swimming, tail suspension, and sugar water preference tests, to ascertain their neurological deficit score. In addition to neurological testing, the study turned its focus to inflammatory factors, measuring protein expression related to the JAK/STAT3-GSK3β/PTEN/Akt pathway. Researchers also used transmission electron microscopy to observe the synaptic ultrastructure after treatment. Lastly, in an in vitro stroke depression model, scientists used flow cytometry to demonstrate that microglia polarization to the M1 phenotype could be reversed with the treatment of GSK3β overexpression virus, Chaihu-Shugan-San, or a JAK-STAT3 inhibitor. The overall findings concluded that Chaihu-Shugan-San provides a beneficial therapeutic effect on a model of post-stroke depression and works through the activation of the JAK/STAT3-GSK3β/PTEN/Akt pathway, indicating that its beneficial effects are due to suppression of neuroinflammation.