Identification of hub genes and candidate herbal treatment in obesity through integrated bioinformatic analysis and reverse network pharmacology

Abstract

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.

Targeting PI3K/AKT signaling pathway in obesity

“…The first-line antidiabetic drug metformin is a classic example as it is a derivative of the natural compound galegine isolated from Galega officinalis L. (Leguminosae), a plant traditionally used for the treatment of diabetes [111]. The increased research interest in natural compounds that fights against obesity has provided solid evidence that PI3K/AKT pathway modulation is involved in the anti-obesity effect of numerous plant extracts and secondary metabolites [4,7,110]. For instance, extract from Garcinia cambogia Roxb.…”

“…Medicinal plants have been used for centuries as a source of potent bioactive compounds that target specific pathologies. Many studies have highlighted the ability of both plant extracts [1][2][3], or specific secondary metabolites [4][5][6][7] to manipulate the pathophysiological mechanisms involved in obesity development. The potential of natural compounds in obesity management by modulation of different molecular pathways has been previously reviewed in detail [8].…”

Untargeted metabolomics-based network pharmacology reveals fermented brown rice towards anti-obesity efficacy

“…Network pharmacology is a novel and effective approach for investigating the pharmacological process and revealing the functions and behaviors of sophisticated biological systems. Differentially expressed genes (DEGs) and hub genes can be used to study disease-related signaling networks and processes to predict targeted drugs 12 . For almost three decades, molecular docking has been a significant method for drug discovery, leading to the identification and development of many new drugs.…”

The combination of Ephedrae herba and coixol from Coicis semen attenuate adiposity via glucocorticoid receptor regulation

“…For instance, Ma et al extracted meaningful gene sets of human hepatocellular carcinoma (HCC) from a public microarray database to compare the outputs with the therapeutic targets of baicalein, which is a major compound of Scutellaria baicalensis 19 . In a recent study, the bioinformatics analysis results of DEGs obtained from the microarray pro ling data and the NP analysis technique were used to inversely suggest herbal medicine candidates to treat obesity 20 .…”