Elucidating the Mechanism of Emodin in Treating Post-Stroke Depression Through Network Pharmacology and Animal Experiments

Objective

Evaluate the mechanism of Emodin therapy for Post-stroke depression (PSD) using network pharmacology and animal experiments.

Methods

Firstly, the effectiveness of Em in treating PSD was confirmed by constructing a PSD rat model. Then, network pharmacology and molecular docking techniques were used to analyze the potential signaling pathways and targets of Em therapy for PSD. Further exploration and validation were conducted using the PSD rat model. Finally, the expressions of tissue plasminogen activator (tPA), matrix metallopeptidase-9 (MMP9), furin, and proprotein convertases (PC) in the hippocampus and medial prefrontal cortex (mPFC) were further detected.

Results

Em exhibited significant neuroprotective and antidepressant effects on PSD. Network pharmacology analysis revealed that Em may exert pharmacological effects on PSD through 47 core targets. These targets were involved in multiple signaling pathways. Molecular docking studies demonstrated that Em had a strong binding affinity for core targets. Animal experiments further indicated that Em could regulate the expression of precursor brain-derived neurotrophic factor (proBDNF) and mature BDNF (mBDNF) in the hippocampus and mPFC, ameliorating apoptosis. In addition, Em could upregulate the expression of tPA gene and protein in the hippocampus and mPFC, as well as upregulate the expression of Furin gene and protein in the mPFC. This confirmed that the balance regulation of proBDNF/mBDNF depends on tPA and Furin.

Conclusion

The therapeutic effects of Em on PSD are multi-targets and multi-pathways. Em may exert therapeutic effects on PSD by binding to the core target, BDNF. The mechanism may be to regulate the balance proBDNF/mBDNF via tPA and Furin, improving apoptosis.