ABSTRACT
Objective:To study the mechanism of astragaloside Ⅳ in the treatment of ischemic stroke by means of network pharmacology. Method:The targets of astragaloside Ⅳ were predicted using Swiss Target Prediction platform, and the targets of ischemic stroke were retrieved using GeneCards, Therapeutic Target Database (TTD), Traditional Chinese Medicine Integrated Database (TCMID) and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) databases. The potential targets of astragaloside Ⅳ acting on ischemic stroke were obtained by the intersection of the targets of astragaloside Ⅳ and ischemic stroke. STRING platform was used to build protein-protein interaction (PPI) network, and eigenvalues were calculated through network topology analysis to screen core targets. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the related targets in DAVID database. Finally, molecular docking verification was conducted to further clarify the core targets of astragaloside Ⅳ acting on ischemic stroke. Result:The 44 common targets were obtained after the intersection of the targets of astragaloside Ⅳ and ischemic stroke. PPI network topology analysis showed that RAC-alpha serine/threonine-protein kinase (Akt1), renin (REN), epidermal growth factor receptor (EGFR), vascular endothlial growth factor A (VEGFA) and neuronal proto-oncogene tyrosine-protein kinase (SRC) were the core targets of astragaloside Ⅳ in the treatment of ischemic stroke. Enrichment analysis results of KEGG pathway showed that the pathways of astragaloside Ⅳ acting on ischemic stroke involved the neuroactive ligand-receptor interaction pathway, cGMP-PKG signaling pathway, calcium signaling pathway, Rap1 signaling pathway, PI3K/Akt signaling pathway, etc. Conclusion:Astragaloside Ⅳ may promote angiogenesis and inhibit platelet activity by acting on Akt1, REN, EGFR, VEGFA, SRC, thus improving cerebral blood flow. It can also inhibit the apoptosis of ischemic brain tissue cells and inflammation to reduce the damage of nerve function, and finally treat ischemic stroke. This study provides ideas and guidance for further exploring the mechanism of astragaloside Ⅳ in the treatment of ischemic stroke.
ABSTRACT
For rheumatoid arthritis, glucocorticoids or immunosuppressive agents are currently used in clinical treatment, but long-term use of these drugs has large side effect on humans, and immunosuppressive agents are expensive. To a certain extent, its wide application is limited. The treatment of rheumatoid arthritis with traditional Chinese medicine(TCM) has a long history and little toxic and side effect, but its specific mechanism of action needs further exploration. The process of autophagy is an active biological process in which cells themselves are stimulated by the outside world through intracellular signal transduction to maintain a stable internal environment. Its abnormality is involved in the occurrence of many diseases. At present, studies have shown that abnormal autophagy is closely related to the occurrence and development of rheumatoid arthritis, which can interfere with the pathological changes of RA pannus formation, synovial inflammation and bone destruction and affect the disease process. In recent years, many studies have found that traditional Chinese medicine and its active ingredients can affect the pathological development of rheumatoid arthritis by regulating autophagy. This article investigates the relevant literature on the intervention of rheumatoid arthritis by regulating autophagy through using TCM, with a view to providing new ideas for basic research, new drug development and clinical treatment of rheumatoid arthritis.