Polyphenols rich Passiflora leschenaultii leaves modulating Farnesoid X Receptor and Pregnane X Receptor against paracetamol-induced hepatotoxicity in rats

Biomed Pharmacother. 2017 Apr:88:1114-1121. doi: 10.1016/j.biopha.2017.01.156. Epub 2017 Feb 10.

Abstract

The hepatoprotective effect of P. leschenaultii. (DC) leaves was investigated in rats under paracetamol induced oxidative stress. Leaf acetone extract (200 and 400mg/kg) were administered daily via gavage for 14days before paracetamol (2000mg/kg, p.o.) treatment. After the experiment, the levels of serum biochemical parameters and enzymatic antioxidant levels were determined. Furthermore, liver tissues were analyzed histopathologically. Additionally, the molecular docking studies of the identified compounds against PXR and FXR proteins were also performed. The assessment revealed that the acetone extract significantly reduced the elevated levels of SGPT, SGOT and ALP in serum. Moreover, the enzymatic antioxidants such as SOD, CAT and LPO were also retained normally by the plant extract. From histopathological analysis, it was clearly evident that the cellular architecture of plant extract treated rat liver tissues were not affected by the paracetamol induction at the higher dose. The results of docking studies also revealed that the identified compounds showed steric interactions (between nonpolar atoms) with amino acid groups. Collectively, the present study suggests that P. leschenaultii leaves extract protects the liver from paracetamol induced hepatic damage.

Keywords: Caffeic acid; FXR; Hepatoprotective; PXR; Paracetamol; Rutin.

MeSH terms

  • Acetaminophen / adverse effects*
  • Animals
  • Antioxidants / metabolism
  • Biomarkers / blood
  • Body Weight / drug effects
  • Liver Diseases / blood
  • Liver Diseases / drug therapy*
  • Liver Diseases / enzymology
  • Male
  • Molecular Docking Simulation
  • Organ Size / drug effects
  • Passiflora / chemistry*
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Plant Leaves / chemistry*
  • Polyphenols / chemistry
  • Polyphenols / therapeutic use*
  • Pregnane X Receptor
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use
  • Rats, Wistar
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Receptors, Steroid / metabolism*
  • Silymarin / pharmacology
  • Silymarin / therapeutic use

Substances

  • Antioxidants
  • Biomarkers
  • Plant Extracts
  • Polyphenols
  • Pregnane X Receptor
  • Protective Agents
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Silymarin
  • farnesoid X-activated receptor
  • Acetaminophen