Hepatoprotectivity of Panduratin A against liver damage: In vivo demonstration with a rat model of cirrhosis induced by thioacetamide

APMIS. 2018 Sep;126(9):710-721. doi: 10.1111/apm.12878. Epub 2018 Jul 29.

Abstract

This experiment evaluated Panduratin A (PA), a chalcone isolated from Boesenbergia rotunda rhizomes, for its hepatoprotectivity. Rats were subjected to liver damage induced by intra-peritoneal injection of thioacetamide (TAA). PA was tested first for its acute toxicity and then administered by oral gavage at doses 5, 10, and 50 mg/kg to rats. At the end of the 8th week, livers from all rats were excised and evaluated ex vivo. Measurements included alkaline phosphatase (AP), alanine transaminase (ALT), aspartate transaminase (AST) and gamma-glutamyl transferase (GGT), serum platelet-derived growth factor (PDGF) and transforming growth factor (TGF-β1), and hepatic metalloproteinase enzyme (MMP-2) and its inhibitor extracellular matrix protein (TIMP-1). Oxidative stress was measured by liver malondialdehyde (MDA) and nitrotyrosine levels, urinary 8-hydroxy 2- deoxyguanosine (8-OH-dG), and hepatic antioxidant enzyme activities. The immunohistochemistry of TGF-β1 was additionally performed. PA revealed safe dose of 250 mg/kg on experimental rats and positive effect on the liver. The results suggested reduced hepatic stellate cells (HSCs) activity as verified from the attenuation of serum PDGF and TGF-β1, hepatic MMP-2 and TIMP-1, and oxidative stress. The extensive data altogether conclude that PA treatment could protect the liver from the progression of cirrhosis through a possible mechanism inhibiting HSCs activity.

Keywords: Boesenbergia rotunda; Hepatoprotectivity; Panduratin A; cirrhosis; thioacetamide.

MeSH terms

  • Animals
  • Chalcones / therapeutic use*
  • Female
  • Hepatic Stellate Cells / drug effects
  • Liver Cirrhosis, Experimental / drug therapy*
  • Liver Cirrhosis, Experimental / metabolism
  • Male
  • Platelet-Derived Growth Factor / analysis
  • Protective Agents / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Thioacetamide
  • Transforming Growth Factor beta1 / blood

Substances

  • Chalcones
  • Platelet-Derived Growth Factor
  • Protective Agents
  • Transforming Growth Factor beta1
  • Thioacetamide
  • panduratin A