Exploring Active Compounds and Mechanisms of Angong Niuhuang Wan on Ischemic Stroke Based on Network Pharmacology and Molecular Docking

Abstract

Background and Purpose. Angong Niuhuang Wan (ANW) is a traditional Chinese herbal formula that has been widely used for the treatment of ischemic stroke, whereas its underlying therapeutic mechanism remains unclear. The objective of the study is to explore the main bioactive ingredients and interaction mechanism of ANW on ischemic stroke based on the network pharmacology method. Methods. The chemical ingredients of ANW were retrieved from TCMSP, TCMID, and literature. We predicted the potential targets of active ingredients by PubChem, Swiss Target Prediction, and STITCH databases. The targets related to ischemic stroke were retrieved using GeneCards, DisGeNET, DrugBank, TTD, and GEO databases. Subsequently, Venn diagrams were used to identify common targets of active ingredients and ischemic stroke. Protein-protein interaction (PPI) network was structured with STRING platform and Cytoscape 3.8.2. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of key targets were performed in the Metascape database. Finally, molecular docking was conducted by AutoDock Tools and PyMOL software. Results. A total of 2391 targets were identified for 230 active ingredients of ANW, and 1386 of them overlapped with ischemic stroke targets. The key active ingredients were mainly quercetin, β-estradiol, berberine, wogonin, and β-sitosterol, and the key targets were also identified, including IL-6, AKT1, MAPK3, PIK3CA, and TNF. The biological process (BP) results indicated that ANW may have therapeutic effects through response oxidative stress, inflammatory response, cellular response to lipid, and response to nutrient levels. Furthermore, the ingredients of ANW were predicted to have therapeutic effects on ischemic stroke via the HIF-1 signaling pathway, FoxO signaling pathway, chemokine signaling pathway, fluid shear stress and atherosclerosis, and neurotrophin signaling pathway. The molecular docking results all showed that the core ingredients were strong binding activity with the core targets. Conclusion. In conclusion, the bioinformatics and pharmacological results reveal that counteracting oxidative stress, suppressing inflammation, inhibiting the development of AS, and even protecting neurological function are critical pathways for ANW in the treatment of ischemic stroke. These results may help to elucidate the mechanism of ANW on ischemic stroke for experimental studies and clinical applications.

Integrating serum metabolomics and network analysis to explore the antidepressant activity of crocin in rats with chronic unexpected mild stress-induced depression

“…Subsequently, the ligand molecularly docked to the receptors using AutoDock, and PyMOL software ( https://pymol.org/2/ ) was used for network visualization (Zhang et al. 2022 ).…”

Metabolomics: A useful tool for ischemic stroke research

“…Additionally, Zhang et al. [ 133 ] used network pharmacology and molecular docking methods to study AGNHW, which identified quercetin, β-estradiol, berberine, baicalein and β-sitosterol as the main active ingredients and identified the key targets, including interleukin 6 (IL-6), AKT1, mitogen-activated protein kinase 3 (MAPK3), PIK3CA and tumor necrosis factor (TNF). Until now, the use of metabolomics to study the active ingredient of AGNHW and its application in ischemic stroke has not been reported.…”

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“…The potential therapeutic target genes were ranked according to the degree value, and the targets and active ingredients with higher degree values were screened. [24] 2.4. Gene ontology and kyoto encyclopedia of genes and genomes analyses…”