Eugenol Promotes Immune Function and Survival Rate in Cecal Ligation Puncture Induced Sepsis Rat Model by Targeting A2A Receptor to Regulate Oxidative Stress Pathway

J Biochem Mol Toxicol. 2025 Sep;39(9):e70481. doi: 10.1002/jbt.70481.

Abstract

This study investigates the potential protective effects of eugenol on cecal ligation puncture (CLP) induced sepsis rat model. CLP was used to induce sepsis in rats and then treated with eugenol at doses of 25 and 50 mg/kg, i.p. for a duration of 7 days. Effects of eugenol was observed on survival rates, markers of oxidative stress, inflammatory cells, and markers in rats. Further network pharmacology study was performed to assess the possible targets for eugenol in the management of sepsis. An interaction study of selected proteins, that is, ADORA2A and HDAC8, with eugenol was observed with a docking study. The eugenol-treated group showed an improvement in the survival rate in the sepsis group of rats. Treatment with eugenol ameliorates oxidative stress, inflammatory mediators, and cells in sepsis rats. Histopathological changes (spleen and lung tissue) were observed to be ameliorates in group of rats treated with eugenol versus the sepsis group. Network pharmacology suggest the 14 common target of interaction between eugenol and sepsis, which was further observed for immunomodulation molecular pathway of sepsis with STRING pathway and gene ontology study. Docking study shows binding strength of ADORA2A-eugenol and HDAC8-eugenol complex was observed to be -6.5 and -5.6 kcal/mol, respectively. Data of investigation concludes that eugenol enhances survival rate in sepsis in rats by reducing inflammation and oxidative stress, as it promotes the immune cell function and neutrophil trapping to xenobiotics and is digested by enhancing oxidative stress in immune cells.

Keywords: eugenol; immune cells; inflammation; oxidative stress; sepsis; survival rate.

MeSH terms

  • Animals
  • Cecum* / injuries
  • Cecum* / surgery
  • Disease Models, Animal
  • Eugenol* / pharmacology
  • Eugenol* / therapeutic use
  • Ligation
  • Male
  • Molecular Docking Simulation
  • Oxidative Stress* / drug effects
  • Punctures
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Adenosine A2A* / chemistry
  • Receptor, Adenosine A2A* / metabolism
  • Sepsis* / drug therapy
  • Sepsis* / immunology
  • Sepsis* / metabolism
  • Sepsis* / pathology
  • Survival Rate

Substances

  • Eugenol
  • Receptor, Adenosine A2A