Investigation into the potential mechanism and molecular targets of Fufang Xueshuantong capsule for the treatment of ischemic stroke based on network pharmacology and molecular docking

Abstract

Fufang Xueshuantong (FFXST) capsule is a traditional Chinese medicine (TCM) preparation used to activate blood circulation, resolve stasis, benefit qi, and nourish yin in clinical practice. However, its potential mechanism and molecular targets after ischemic stroke (IS) have not been investigated. The aim of this research was to investigate the molecular mechanisms of FFXST in the treatment of IS based on network pharmacology and molecular docking. We used the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) to collect candidate compounds of four herbs in FFXST; disease-related differential genes were screened using the Gene Expression Omnibus (GEO) database, and a compound-disease network was created using Cytoscape 3.8.2 software. The topological analysis of the protein-protein interaction (PPI) network was then created to determine the candidate targets of FFXST against IS. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using the clusterProfiler package in R. The gene-pathway network of FFXST against IS was created to obtain the key target genes. Molecular docking was used to validate the core targets using AutoDock Vina 1.1.2. A total of 455 candidate compounds of FFXST and 18,544 disease-related differential genes were screened. Among them, FFXST targets for IS treatment had 67 active compounds and 10 targets in the PPI network related to STAT1, STAT3, and HIF1A. The biological processes of GO analysis included the regulation of reactive oxygen species metabolic process, cellular response to chemical stress, regulation of angiogenesis, regulation of vasculature development, positive regulation of cytokine production, and response to oxidative stress. The KEGG enrichment analysis showed that Kaposi sarcoma-associated herpesvirus infection, microRNAs in the cancer signaling pathway, Th17 cell differentiation, and HIF-1 signaling

Network pharmacology and experimental study of phenolic acids in salvia miltiorrhiza bung in preventing ischemic stroke

“…It is reported that salvianolic acids promoted angiogenesis and neurological recovery by regulating STAT3 signaling pathway after ischemia (Li et al, 2017). In addition, Wang et al proved that the core target of ischemic stroke in Fufang Xueshuantong treatment was STAT1, STAT3 through the method of network pharmacology, which was consistent with our predicted results (Wang et al, 2022). Therefore, these core genes inhibit inflammation and apoptosis, protect vascular endothelial injury in order to inhibit thrombosis in ischemic stroke rats.…”

“…Network pharmacology seeks targets of drugs and diseases from public databases to analyze the mechanism of drug action from the perspective of biological balance, which helps to elucidate the interactions among compounds, genes, and diseases (Li et al, 2020;Wang et al, 2021a;Wang et al, 2022). In this paper, we first used the method of network pharmacology to predict the effect of phenolic acids in the prevention of ischemic stroke, and then screened the antiplatelet effect through in vitro antiplatelet experiment.…”

Protective effects of Gypenoside XVII against cerebral ischemia/reperfusion injury via SIRT1-FOXO3A- and Hif1a-BNIP3-mediated mitochondrial autophagy

“…Due to the complexity of the pathogenesis of ischemic stroke, the limitations of therapeutic drugs and the very large international and domestic needs, an increasing number of researchers are studying traditional Chinese medicines as important ways to treat ischemic stroke [9][10][11]. Notoginseng leaf triterpenes (PNGL), a total saponin extract of Panax notoginseng stems and leaves, attenuates neuronal apoptosis [12] and ameliorates mitochondrial oxidative injury caused by ischemia [13,14].…”

The signaling pathways of selected traditional Chinese medicine prescriptions and their metabolites in the treatment of diabetic cardiomyopathy: a review

“…Bunge, and Scrophularia ningpoensis Hemsl . It has the function of promoting blood circulation, removing blood stasis, tonifying qi, and nourishing yin and could be used clinically for the treatment of stable angina pectoris and cerebrovascular diseases ( Peng et al, 2022 ; Wang et al, 2022 ). Peng et al (2022) observed the intervention effect of FXST on DCM by establishing a STZ-induced diabetic rat model.…”

“…Clinically, DCM can be divided into two stages according to its typical features. The early stage is characterized by diastolic damage and left ventricular hypertrophy without vascular defects, and the late stage is mainly characterized by systolic dysfunction and myocardial fibrosis ( Wang et al, 2022 ; Zhou et al, 2023 ). Although the pathogenesis of DCM is complex, after long-term exploration, scholars generally believe that the occurrence and development of DCM is mainly related to glucose and lipid metabolism disorders, microvascular endothelial dysfunction, apoptosis, advanced glycation end product (AGE) deposition, myocardial inflammation, and oxidative stress.…”