Active ingredients and molecular targets of Taraxacum mongolicum against hepatocellular carcinoma: network pharmacology, molecular docking, and molecular dynamics simulation analysis

PeerJ. 2022 Jul 18:10:e13737. doi: 10.7717/peerj.13737. eCollection 2022.

Abstract

Background: Taraxacum mongolicum (TM) is a widely used herb. Studies have reported that TM exhibits growth-inhibitory and apoptosis-inducing on multiple tumors, including hepatocellular carcinoma (HCC). The active ingredients, targets, and molecular mechanisms of TM against HCC need to be further elucidated.

Methods: We identified the active ingredients and targets of TM via HERB, PubChem, SwissADME, SwissTargetPrediction, and PharmMapper. We searched HCC targets from GeneCards, Comparative Toxicogenomics Database (CTD), and DisGeNET. Then, the intersection of drug targets and disease targets was uploaded to the STRING database to construct protein-protein interactions (PPI) networking whose topology parameters were analyzed in Cytoscape software to screen hub targets. Next, we used Metascape for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and we employed AutoDock vina, AMBER18 and PyMOL software along with several auxiliary tools for molecular docking and molecular dynamics (MD) simulation. Finally, based on the in silico findings, cellular experiments were conducted to investigate the effect of TM on HSP90AA1 gene expression.

Results: A total of 228 targets and 35 active ingredients were identified. Twenty two hub targets were selected through PPI networking construction for further investigation. The enrichment analysis showed that protein kinase binding, mitogenactivated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways were mainly involved. Molecular docking and MD simulation results supported good interaction between HSP90 protein and Austricin/Quercetin. The in vitro assay showed that TM inhibited the proliferation of HepG2 cells and the expression of HSP90AA1 gene.

Conclusions: This study is the first to use network pharmacology, molecular docking, MD simulation and cellular experiments to elucidate the active ingredients, molecular targets, and key biological pathways responsible for TM anti-HCC, providing a theoretical basis for further research.

Keywords: Hepatocellular carcinoma; Molecular docking; Molecular dynamics simulation; Network pharmacology; Taraxacum Mongolicum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular* / drug therapy
  • Liver Neoplasms* / drug therapy
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Network Pharmacology
  • Phosphatidylinositol 3-Kinases
  • Protein Kinases
  • Taraxacum*

Substances

  • Phosphatidylinositol 3-Kinases
  • Protein Kinases

Grants and funding

This work was supported by the Sichuan Province Key R&D Plan Project (No. 2020YFS0301) and the Sichuan Province Applied Basic Research Project (2021YJ0253). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.