Ehretia laevis mitigates paracetamol- induced hepatotoxicity by attenuating oxidative stress and inflammation in rats

Int Immunopharmacol. 2024 Dec 25;143(Pt 3):113565. doi: 10.1016/j.intimp.2024.113565. Epub 2024 Nov 5.

Abstract

Hepatotoxicity is caused due to intake of drug or any chemical above the therapeutic range or as overdose. Current therapies for the management of hepatotoxicity are associated with several side effects. The present study was envisaged to explore the hepatoprotective potential of Ehretia laevis (E. laevis) in paracetamol (PCM) induced hepatotoxicity. All the plant extracts and fractions were evaluated for antioxidant and antiproliferative potential using various in vitro assays. Hepatotoxicity was induced in rats using a standardized single oral dose of PCM (3 g/kg). The aqueous fraction of E. laevis (AFEL) exhibited significant antioxidant and antiproliferative activity as compared to methanol extract of E. laevis (MEEL) in vitro. Moreover, treatment with AFEL (25, 50 and 100 mg/kg) decreased serum hepatic markers, attenuate the oxidative stress, inflammation and histopathological changes. LC-MS analysis of AFEL showed the presence of rutin, quercetin and kaempferol. Rutin was found to be in higher concentration, therefore it was docked on TNF-α. Its overall binding mode supports its capability to make complex with TNF-α. The finding of the study suggested significant antioxidant, antiproliferative, and hepatoprotective potential of E. laevis in paracetamol induced hepatotoxicity which could be attributed to the presence of various polyphenols.

Keywords: Antiproliferative; DNA nicking; E. laevis; Hepatotoxicity; Inflammation; Polyphenols.

MeSH terms

  • Acetaminophen*
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Antioxidants* / pharmacology
  • Antioxidants* / therapeutic use
  • Cell Proliferation / drug effects
  • Chemical and Drug Induced Liver Injury* / drug therapy
  • Chemical and Drug Induced Liver Injury* / metabolism
  • Chemical and Drug Induced Liver Injury* / pathology
  • Humans
  • Inflammation / drug therapy
  • Liver* / drug effects
  • Liver* / metabolism
  • Liver* / pathology
  • Male
  • Oxidative Stress* / drug effects
  • Plant Extracts* / pharmacology
  • Plant Extracts* / therapeutic use
  • Rats
  • Rats, Wistar
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Acetaminophen
  • Plant Extracts
  • Antioxidants
  • Anti-Inflammatory Agents
  • Tumor Necrosis Factor-alpha