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1.
Medicine (Baltimore) ; 103(12): e37592, 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38518018

ABSTRACT

Bronchial asthma (BA) is a chronic respiratory disease closely related to immune system dysregulation. Traditional Chinese medicine has long adopted the strategy of Sanao decoction in the treatment of bronchial asthma. However, due to the multi-target and multi-pathway characteristics of Chinese herbal medicine, we are still unclear about the specific mechanism of Sanao decoction in treating bronchial asthma. To investigate the mechanism of action of Sanao decoction in the treatment of BA using a network pharmacology approach and preliminary validation by molecular docking technology. Traditional Chinese medicine systems pharmacology database and analysis platform and UniProt databases were used to search the active ingredients and targets of Sanao decoction, and BA-related targets were screened according to GeneCards and online Mendelian inheritance in man database databases. The intersection targets were imported into the STRING database to construct a protein-protein interaction network, and Cytoscape 3.9.1 software was used to screen out hub genes. This study also constructed a "drug-ingredient-target" visual network diagram. Gene Ontology and Kyoto Encyclopedia of Genomes enrichment analysis was performed on targets in the protein-protein interaction network using the ClusterProfiler package in R, with a P value < .05. Autodock software was used for molecular docking to complete the preliminary verification of core components and targets. A total of 73 active compounds and 308 targets of Sanao decoction, including 1640 BA-related disease targets, were retrieved from mainstream databases. Gene Ontology analysis and Kyoto encyclopedia of genes and genomes enrichment analysis suggested that Sanao decoction plays a role in the treatment of BA through signaling pathways such as PI3K-Akt, MAPK, and IL-17 signaling pathway. The 9 core goals represent the main elements related to Sanao decoction in the treatment of BA. Subsequently, the molecular docking results showed that most of the active compounds of Sanao decoction have strong binding efficiency with the hub gene. Sanao decoction has a key impact on BA through multiple channels. In summary, this intricate network reflects the potential of Sanao decoction in treating BA, a multifactorial disease. In addition, this study laid the foundation for further in vivo and in vitro experimental research and expanded the clinical application of Sanao decoction.


Subject(s)
Asthma , Bronchial Diseases , Drugs, Chinese Herbal , Humans , Molecular Docking Simulation , Network Pharmacology , Phosphatidylinositol 3-Kinases , Asthma/drug therapy , Asthma/genetics , Databases, Genetic , Medicine, Chinese Traditional , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use
2.
Oncol Rep ; 45(6)2021 06.
Article in English | MEDLINE | ID: mdl-33846811

ABSTRACT

The aim of the present study was to investigate the synergistic effect of LY294002 (a PI3K inhibitor) and ABT199 (a BCL2 inhibitor) on the cell cycle in acute myeloid leukemia (AML). The optimal concentration and duration of combined LY294002 and ABT199 were determined in human erythroleukemia (K562), promyelocytic leukemia (HL60) and myeloid leukemia (KG1a) cell lines. The mRNA and protein expression levels of cell cycle­related molecules, including S­phase kinase­associated protein 2 (Skp2), p27, BCL2, Bax, cleaved caspase 3 (caspase­3) and caspase 9 (caspase­9) were detected via reverse transcription­quantitative PCR and western blot analysis, respectively. At the molecular level, LY294002 and ABT199 combination treatment significantly downregulated Skp2, Bcl2, procaspase­3 and procaspase­9 expression levels, but markedly upregulated p27, Bax, cleaved caspase­3 and caspase­9 expression levels in K562, HL­60 and KG1a cells. The results of the present study demonstrated that LY294002 and ABT199 combination treatment may serve as a novel therapeutic strategy for AML.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Cell Cycle/drug effects , Chromones/pharmacology , Leukemia, Myeloid, Acute/drug therapy , Morpholines/pharmacology , Sulfonamides/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bridged Bicyclo Compounds, Heterocyclic/therapeutic use , Cell Cycle/genetics , Chromones/therapeutic use , Dose-Response Relationship, Drug , Drug Synergism , Gene Expression Regulation, Leukemic/drug effects , HL-60 Cells , Humans , K562 Cells , Morpholines/therapeutic use , Phosphoinositide-3 Kinase Inhibitors/pharmacology , Phosphoinositide-3 Kinase Inhibitors/therapeutic use , Sulfonamides/therapeutic use
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