RESUMEN
Obesity is a global epidemic elevating the risk of various metabolic disorders. As there is a lack of effective drugs to treat obesity, we combined bioinformatics and reverse network pharmacology in this study to identify effective herbs to treat obesity. We identified 1011 differentially expressed genes (DEGs) of adipose tissue after weight loss by analyzing five expression profiles (GSE103766, GSE35411, GSE112307, GSE43471, and GSE35710) from the Gene Expression Omnibus (GEO) database. We identified 27 hub genes from the protein-protein interaction (PPI) network by performing MCODE using the Search Tool for the Retrieval of Interacting Genes (STRING) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that these hub genes have roles in the extracellular matrix-receptor interaction, cholesterol metabolism, PI3K-Akt signaling pathway, etc. Ten herbs (Aloe, Portulacae Herba, Mori Follum, Silybum Marianum, Phyllanthi Fructus, Pollen Typhae, Ginkgo Semen, Leonuri Herba, Eriobotryae Folium, and Litseae Fructus) targeting the nine hub genes (COL1A1, MMP2, MMP9, SPP1, DNMT3B, MMP7, CETP, COL1A2, and MUC1) using six ingredients were identified as the key herbs. Quercetin and (-)-epigallocatechin-3-gallate were determined to be the key ingredients. Lastly, Ingredients-Targets, Herbs-Ingredients-Targets, and Herbs-Taste-Meridian Tropism networks were constructed using Cytoscape to elucidate this complex relationship. This study could help identify promising therapeutic targets and drugs to treat obesity.
Asunto(s)
Biología Computacional , Metaloproteinasa 2 de la Matriz , Colesterol , Perfilación de la Expresión Génica , Humanos , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 7 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/genética , Farmacología en Red , Obesidad/tratamiento farmacológico , Obesidad/genética , Fosfatidilinositol 3-Quinasas/genética , Mapas de Interacción de Proteínas/genética , Proteínas Proto-Oncogénicas c-akt/genética , QuercetinaRESUMEN
PURPOSE: The purpose of this study was to determine the effect of Euphorbia lunulata Bge extract on the proliferation of human hepatoma HepG2 cell line. METHODS: Different dilutions of Euphorbia lunulata Bge extract were used to treat human hepatoma HepG2 cells. Hoechst 33258 and PI-staining fluorescence microscopy were utilized to observe the nuclear morphological changes of apoptotic cells. Flow cytometry was used to detect the rates of apoptosis and apoptotic peaks. Western blotting was performed to analyze the subcellular distribution of cytochrome C. RESULTS: The Euphorbia lunulata Bge extract was found to inhibit the proliferation of human hepatoma HepG2 cells via a time and concentration-dependent manner. CONCLUSION: Altogether, the results suggest that the Euphorbia lunulata Bge extract is effective in inhibiting the proliferation of human hepatoma HepG2 cells and inducing cell apoptosis. The mechanism may be related to the mitochondrial pathways or cellular apoptosis pathways.