Potential Mechanism by which Eriodictyol Protects against Doxorubicininduced Cardiotoxicity based on Network

Chunmeng Qin1,2, Mei Sun1, Feng Lv1

  • 1Department of Pharmacy, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, 401120, China.

Abstract

Insights

Eriodictyol (ERD) may protect against doxorubicin-induced cardiotoxicity (DIC) by targeting multiple pathways, particularly the ROS pathway. This study elucidates ERD's protective mechanisms for potential clinical use.

Area of Science:

  • Pharmacology
  • Computational Biology
  • Cardiovascular Research

Background:

  • Doxorubicin (DOX) is a vital chemotherapy drug, but its use is limited by cardiotoxicity (DIC).
  • Eriodictyol (ERD) exhibits cardioprotective properties, yet its mechanism against DIC remains unclear.

Purpose of the Study:

  • To investigate the underlying mechanisms of eriodictyol's protective effects against doxorubicin-induced cardiotoxicity.
  • To identify key molecular targets and pathways involved in ERD's cardioprotection.

Main Methods:

  • Utilized network pharmacology by integrating data from multiple databases (TCMSP, PharmMaper, etc.) to identify ERD and DIC targets.
  • Constructed a protein-protein interaction network and performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses.
  • Validated interactions using molecular docking and molecular dynamics simulations.

Main Results:

  • Identified 43 intersecting ERD-DIC targets, highlighting 6 key targets.
  • Functional enrichment analysis revealed significant involvement in biological processes, cellular components, and molecular functions.
  • Molecular docking and dynamics simulations confirmed strong binding affinities between ERD and critical targets, especially within the ROS pathway.

Conclusions:

  • Systematic network pharmacology analysis suggests ERD mitigates DIC via multiple targets and pathways.
  • The ROS pathway is identified as a potentially crucial mediator of ERD's cardioprotective effects.
  • Findings offer a foundation for further research and clinical application of ERD in managing DIC.

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