Network pharmacology integrated with molecular docking technology to reveal the potential mechanism of Shuganfang against drug-induced liver injury

by Selleckchem | Jan 12 2024

This study aimed to investigate the active composition and mechanism of the Shuganfang (SGF) in treating drug-induced liver injury (DILI) using network pharmacology and molecular docking. The potential active ingredients and targets of SGF were obtained from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) database. DILI-related targets were queried from various databases including GEO, GeneCards, OMIM, NCBI, and DisGeNET. The STRING database was used to establish a protein-protein interaction (PPI) network. DAVID was utilized for conducting gene ontology (GO) function enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses. The data visualization and analysis of herb-ingredient-target and disease-pathway-target-ingredient networks were conducted using Cytoscape software (version 3.7.2). PyMoL and AutoDock software was used to select the best binding target for molecular docking. A total of 177 active ingredients,126 targets and 10112 disease targets were obtained, including 122 intersection targets. The identified potential active ingredients consisted of quercetin, kaempferol, luteolin, tanshinone IIa, nobiletin, isorhamnetin, beta-sitosterol and naringenin. The core targets implicated in the study were IL6, estrogen receptor 1 (ESR1), hypoxia-inducible factor alpha subunit 1 (HIF1A), MYC and vascular endothelial growth factor A (VEGFA). KEGG analysis revealed that the treatment of DILI with SGF mainly acted through apoptosis, the PI3K-Akt signaling pathway, and the tumor necrosis factor (TNF) signaling pathway. Furthermore, the binding affinities between the potential ingredients and the core targets were subsequently confirmed through molecular docking experiments. The findings indicated that the docking outcomes remained consistent and demonstrated a favorable capacity for binding. SGF exerts a therapeutic effect on DILI through multiple active ingredients, multiple targets and multiple pathways. Our findings contribute to a positive investigation and establish a theoretical basis for further extensive exploration of SGF as a potential treatment for DILI in future research.

Comments:

That's an impressive study! It seems like a comprehensive approach was taken to explore the therapeutic potential of Shuganfang (SGF) in treating drug-induced liver injury (DILI) using network pharmacology, molecular docking, and bioinformatic analyses.

The utilization of databases like TCMSP for active ingredients and targets, along with multiple sources for DILI-related targets, helps create a broad understanding of the interactions and mechanisms involved. Constructing protein-protein interaction networks and performing enrichment analyses using tools like STRING and DAVID allows for a deeper comprehension of the pathways and biological processes affected.

Identifying specific active ingredients such as quercetin, kaempferol, luteolin, and others, along with core targets like IL6, ESR1, HIF1A, MYC, and VEGFA, provides valuable insights into the molecular interactions underlying SGF's efficacy in treating DILI.

The KEGG pathway analysis revealing the involvement of apoptosis, the PI3K-Akt signaling pathway, and the TNF signaling pathway in the treatment of DILI with SGF further elucidates the complex mechanisms through which SGF might exert its therapeutic effects.

The validation of binding affinities through molecular docking experiments strengthens the study by providing evidence of potential interactions between the identified active ingredients and core targets.

Overall, this study not only sheds light on the potential mechanisms of SGF in treating DILI but also lays the groundwork for further research and clinical exploration of SGF as a potential therapeutic option for this condition.