Exploring the Therapeutic Efficacy and Pharmacological Mechanism of Guizhi Fuling Pills on Ischemic Stroke: A Meta-Analysis and Network Pharmacology Analysis

Abstract

Abstract The roles of Guizhi Fuling Pills (GZFL) on the treatment of ischemic stroke (IS) are still controversial, and its pharmacological mechanism remains unclear. We aimed to investigate the efficacy of GZFL for IS and reveal the underlying mechanism using meta-analysis and network pharmacology methods. Eight electronic databases were searched up to November 20, 2023. A meta-analysis was conducted using Review Manager 5.4.1 software. The chemical compounds of GZFL were obtained using TCMSP, BATMAN-TCM, and ETCM, and their putative targets were predicted using Swiss Target Prediction database. IS-related targets were collected using DisGeNet, Genecards, and DrugBank. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed in the Metascape. Molecular docking was carried out using AutoDock Tools and PyMOL software. Compared with conventional medical treatment alone, GZFL plus conventional medical treatment could significantly improve the clinical total effective rate and NIHSS scores. The addition of GZFL also improved whole blood high shear viscosity, whole blood low shear viscosity, and plasma fibrinogen, TNF-α and IL-6 levels. The top key active compounds included quercetin, kaempferol, catechin, and beta-sitosterol, and SRC, MAPK1, TP53, JUN, RELA, AKT1, and TNF were main core targets. GO analysis mainly included regulation of ion transport, cellular response to lipid, and inflammation response. The core pathways were enriched in lipid and atherosclerosis, cAMP, calcium, IL-17, and MAPK signaling pathways. The key active compounds had good affinity with the core targets. This study showed that GZFL displays anti-inflammatory, anti atherosclerosis and neuroprotective effects for IS patients.