Hepatoprotective effect of artichoke leaf extracts in comparison with silymarin on acetaminophen-induced hepatotoxicity in mice

J Immunoassay Immunochem. 2020;41(1):84-96. doi: 10.1080/15321819.2019.1692029. Epub 2019 Nov 18.


Acetaminophen is a common analgesic-antipyretic agent, which is safe in therapeutic doses but in higher doses can produce hepatic necrosis. The aim of this study is to investigate the hepatoprotective effects of artichoke, silymarin, and both agents in acetaminophen-induced liver damage in mice. Forty male mice were divided into five main groups, (1) control (2) Acetaminophen (APAP) (3) Artichoke leaf extracts (ALE) and APAP (4) silymarin and APAP group (5) ALE, silymarin and APAP groups. Blood samples were collected for the measurement of liver enzymes (ALT, AST, and ALP). The liver was excised, weighed and dissected into two parts, one used for measurement of malondialdehyde (MDA) and glutathione reductase, and the other part used for histopathological examination and assessment of proliferative cell nuclear antigen (PCNA) immunohistochemical expression. APAP group showed a significant increase in liver weight, ALT, AST, ALP, MDA, and PCNA expression with a significant decrease in glutathione reductase in comparison to control group. All these parameters were significantly improved in the three treated groups when compared to APAP group. APAP group showed marked portal inflammation and parenchyma necrosis. Co-administration of ALE and/or silymarin to acetaminophen treated mice showed a significant reduction in PCNA expression compared to APAP group. Both ALE and silymarin co-treatment showed a significant decrease in PCNA percentage to a level near to control group. Artichoke and/or silymarin are suggested to protect against acetaminophen-induced hepatotoxicity in mice by ameliorating liver enzymes, antioxidant effect, decreasing liver damage and proliferation.Abbreviation: ALT, alanine transaminase. AST, aspartate transaminase. ALP, alkaline phosphatase.MDA, malondialdehyde. PCNA, proliferative cell nuclear antigen.

Keywords: Artichoke; PCNA; acetaminophen; hepatotoxicity; immunohistochemistry; silymarin.

Publication types

  • Comparative Study

MeSH terms

  • Acetaminophen
  • Animals
  • 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
  • Cynara scolymus / chemistry*
  • Immunohistochemistry
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Leaves / chemistry*
  • Protective Agents / chemistry
  • Protective Agents / isolation & purification
  • Protective Agents / pharmacology*
  • Silymarin / chemistry
  • Silymarin / pharmacology*


  • Plant Extracts
  • Protective Agents
  • Silymarin
  • Acetaminophen