Identification of hub genes and candidate herbal treatment in obesity through integrated bioinformatic analysis and reverse network pharmacology
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Updated: Aug 26, 2025

Network Pharmacology Prediction and Metabolomics Validation of the Mechanism of Fructus Phyllanthi against Hyperlipidemia
Published on: April 7, 2023
Yuxing Tai1, Hongying Tian1, Xiaoqian Yang2
1Changchun University of Chinese Medicine, Changchun, 130117, China.
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.
Insights
This study identifies ten key herbs and two potent ingredients for obesity treatment by analyzing gene expression and network pharmacology. These findings offer new therapeutic targets and natural drug candidates for combating the global obesity epidemic.
Area of Science:
- Genomics and Bioinformatics
- Pharmacology
- Metabolic Disorders
Background:
- Obesity is a global health crisis with limited effective pharmaceutical treatments.
- Identifying novel therapeutic strategies for obesity is crucial for public health.
Purpose of the Study:
- To identify effective herbs and active ingredients for obesity treatment using bioinformatics and reverse network pharmacology.
- To elucidate the complex relationships between herbs, ingredients, and therapeutic targets for obesity.
Main Methods:
- Analyzed adipose tissue gene expression data from five GEO datasets to identify differentially expressed genes (DEGs).
- Constructed a protein-protein interaction (PPI) network to identify 27 hub genes using MCODE and STRING.
- Performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses.
- Identified ten key herbs targeting nine hub genes with six active ingredients, including Quercetin and (-)-epigallocatechin-3-gallate.
- Utilized Cytoscape to construct network models (Ingredients-Targets, Herbs-Ingredients-Targets, Herbs-Taste-Meridian Tropism).
Main Results:
- Identified 1011 DEGs in adipose tissue post-weight loss.
- Discovered 27 hub genes involved in pathways like extracellular matrix-receptor interaction and cholesterol metabolism.
- Pinpointed ten specific herbs and nine key target genes (e.g., COL1A1, MMP2, CETP) for obesity.
- Confirmed Quercetin and (-)-epigallocatechin-3-gallate as primary active ingredients.
Conclusions:
- This study provides a comprehensive network pharmacology approach to identify natural compounds for obesity.
- The identified herbs and ingredients represent promising therapeutic candidates for obesity management.
- The findings offer potential new targets and drug discovery avenues for metabolic disorders.
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