The mechanism of action of the combination of Astragalus membranaceus and Ligusticum chuanxiong in the treatment of ischemic stroke based on network pharmacology and molecular docking

Abstract

Since 1990, the incidence of stroke has been rising to become the second leading cause of death in the world, posing a huge burden and challenge to society and families. Astragalus membranaceus and Ligusticum chuanxiong (A&L) have been used as traditional Chinese medicine (TCM) prescriptions to treat and prevent the occurrence of ischemic stroke (IS), but their mechanism of action on the disease has not been fully elucidated. The main objective of this study was to reveal the pharmacological mechanism of A&L in the treatment of IS and to perform preliminary validation. The active ingredients of A&L were obtained from the systematic pharmacology platform of traditional Chinese medicine (TCMSP) database, whereas the genes of IS were obtained from 2 major databases, DrugBank and GeneCards. Cytoscape_v3.8.2 was used to construct the TCM-active ingredient and TCM-active ingredient-cross-target-disease relationship maps, and the MCODE plug-in was used to obtain the core genes, whereas the protein-protein interaction maps were obtained from the STRING database. The results of gene ontology and Kyoto encyclopedia of genes and genomes enrichment were obtained using the Hiplot online tool, and the small molecules in the relevant signalling pathways were verified by molecular docking using AutoDock. A&L contained a total of 26 eligible active ingredients, sharing 161 common targets with IS. A total of 58 core genes with 1326 edges were obtained using the MCODE plug-in. Gene ontology and Kyoto encyclopedia of genes and genomes enrichment results showed association with interleukin-17 signaling pathway, lipid and atherosclerosis, tumor necrosis factor signaling pathway, and Toll-like receptor signaling pathway, which mainly mediates the development of inflammatory responses. Furthermore, molecular docking was conducted and most of the components were found to have good binding to the receptors. This study demonstrates that A&L can be used to treat IS by controlling the inflammatory response through multiple targets and multiple pathways, and provides a reference for subsequent trials.

Cytotoxicity of the methanol extracts and compounds of Brucea antidysenterica (Simaroubaceae) towards multifactorial drug-resistant human cancer cell lines

“…The importance of medicinal plants in the search of drugs is well established today [ 5 – 7 ]. Some illustrative anticancer molecules include vinblastine, vincristine, paclitaxel, or camptothecin [ 53 ].…”

“…The exploitation of medicinal plants traditionally used under rigorously well-conducted scientific investigations in vitro, in vivo, or in silico, has contributed significantly to the improvement of human health, with many pharmaceuticals deriving from botanicals [ 5 – 7 ].…”

Identification and Pharmacological Activities of Secondary Metabolites of Phytochemicals

“…to possess antithrombotic and anticoagulant activities [5][6]. Tetramethylpyrazine extracted from Chuanxiong rhizome has been used for treatment of Ischemic stroke [7][8][9]. Quinine extracted from Cinchona tree are used in the treatment of malaria and has served as a source of many other drugs.…”

Exploration of Fuzheng Yugan Mixture on COVID-19 based on network pharmacology and molecular docking

“…Network pharmacology can integrate Chinese medicine, Chinese medicine ingredients and component targets to build the herbal-component-target network. [ 12 , 13 ] This network involved in the analysis has laid the foundation of active ingredients and mechanism of Chinese herbal compound. Molecular docking technology can predict the binding stability between drug and receptor by predicting the interaction mode and binding energy between receptor and drug molecules, which can be used as an important tool for drug screening and design.…”