Mechanistic study of Mongolian medicine Zhachong 13 Pills for ischemic stroke based upon network phar-macology,molecular docking and experimental verification
OBJECTIVE To explore the potential mechanism of Mongolian medicine Zhachong 13 Pills for ischemic stroke through network pharmacology and verify through molecular docking and animal experiments.METHODS The active chemical constituents of Zhachong 13 Pills were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and other databases for target prediction and collection.Online Mendelian Inheritance in Man(OMIM)and other databases were employed for obtaining disease targets,Venny was utilized for obtaining intersection targets and protein-protein interaction(PPI)network was constructed.GO function enrichment and KEGG path enrichment analyses were performed with the database of Metascape.Molecular docking was performed by Autodock Vina.A rat model of ischemic stroke was estab-lished by a ligation of bilateral common carotid artery.Five groups of sham operation,model,Zhachong 13 high-dose,Zhachong 13 low-dose and positive control were designated.High-dose and low-dose groups received a suspension of Zhachong 13 Pills by 0.324 g·kg-1 and 0.162 g·kg-1 respectively.Positive control group had a donepezil solution by 0.45 mg·kg-1.Nerve injury of rats was evaluated at Day 3/7/14/28 post-modeling according to stroke index.After 28-day continuous instillation,brain tissue was harvested for hematoxylin-eosin(HE)stain and serum contents of dopamine(DA)and 5-hydroxytryptamine(5-HT)in rats determined by enzyme-linked immunosorbent assay(ELISA).And the results of network pharmacology were preliminatively verified.RESULTS There were 182 active components of Zhachong 13 Pills,905 targets and 668 common targets for disease effects.Pathway enrichment analysis revealed that the major pathways were cAMP signaling,5-HT-synapses,dopaminergic syn-apses and platelet activation.Nerve function injury score and HE stain indicated that Zhachong 13 Pills could improve brain injury of ischemic stroke.ELISA confirmed that Zhachong 13 Pills could lower the serum contents of DA and 5-HT in ischemic stroke rats.CONCLUSION The potential acting mechanism Zhachong 13 Pills in ischemic stroke rats has been preliminarily verified through network pharmacology and animal experiments.It shall provide rationales for further researches on pharmacodynamic materials and acting mechanisms of Zhachong 13 Pills for ischemic stroke.
Mongolian medicine Zhachong 13 Pillsischemic strokenetwork pharmacologymolecular dockinganimal experiments
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