Dandelion polyphenols protect against acetaminophen-induced hepatotoxicity in mice via activation of the Nrf-2/HO-1 pathway and inhibition of the JNK signaling pathway

Chin J Nat Med. 2020 Feb;18(2):103-113. doi: 10.1016/S1875-5364(20)30011-X.

Abstract

We investigated the liver protective activity of dandelion polyphenols (DP) against acetaminophen (APAP; Paracetamol)-induced hepatotoxicity. Mice were acclimated for 1 week and randomly divided into the following groups (n = 9 per group): Control, APAP, APAP + DP (100 mg·kg-1), APAP + DP (200 mg·kg-1), and APAP + DP (400 mg·kg-1) groups. Mice were pretreated with DP (100, 200, and 400 mg·kg-1) by oral gavage for 7 d before being treated with 350 mg·kg-1 APAP for 24 h to induced hepatotoxicity. Severe liver injury was observed, and hepatotoxicity was analyzed after 24 h by evaluation of biochemical markers, protein expressions levels, and liver histopathology. Pretreatment with DP was able to restore serum liver characteristics (aspartate transaminase, AST; alanine aminotransferase, ALT; alkaline phosphatase, AKP), improve redox imbalance (superoxide dismutase, SOD; glutathione, GSH; malondialdehyde, MDA), and decrease inflammatory factors (tumor necrosis factor-α, TNF-α; interleukin-1β, IL-1β). Pretreatment with DP also significantly inhibited the expression levels of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, DP pretreatment could inhibit the apoptosis of liver cells caused by APAP through up-regulation of Bcl-2 and down-regulation of Bax and caspase-9 protein. DP also down-regulated p-JNK protein expression levels to inhibit APAP-induced mitochondrial oxidative stress and up-regulated the expression of Nrf-2 and its target gene HO-1. The histopathological staining demonstrated that DP pretreatment could inhibit APAP-induced hepatocyte infiltration, congestion, and necrosis. Our results demonstrate that DP pretreatment could protect against APAP-induced hepatic injury by activating the Nrf-2/HO-1 pathway and inhibition of the intrinsic apoptosis pathway.

Keywords: APAP-induced liver injury; Anti-apoptosis; Anti-inflammation; Dandelion polyphenols; JNK pathways; Nrf-2/HO-1 pathways; Oxidative stress.

MeSH terms

  • Acetaminophen / toxicity*
  • Animals
  • Apoptosis / drug effects
  • Biomarkers / blood
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Disease Models, Animal
  • Heme Oxygenase-1 / metabolism
  • MAP Kinase Signaling System / drug effects*
  • Male
  • Membrane Proteins / metabolism
  • Mice
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress / drug effects
  • Plant Extracts / pharmacology*
  • Polyphenols / pharmacology*
  • Taraxacum / chemistry*

Substances

  • Biomarkers
  • Membrane Proteins
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Plant Extracts
  • Polyphenols
  • Acetaminophen
  • Heme Oxygenase-1
  • Hmox1 protein, mouse