Synergistic effect of cyanidin and PPAR agonist against nonalcoholic steatohepatitis-mediated oxidative stress-induced cytotoxicity through MAPK and Nrf2 transduction pathways

Ping Hsiao Shih, Sam Long Hwang, Chi Tai Yeh, Gow Chin Yen

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28 Citations (Scopus)


Nonalcoholic steatohepatitis (NASH) is caused by an elevation in oxidative stress, which might further lead to hepatic fibrogenesis. Importantly, both peroxisome proliferator-activated receptor (PPAR) and nuclear factor erythroid 2-related factor 2 (Nrf2) play roles in modulating oxidative stress-mediated hepatic dysfunction. The objective of this study was to investigate the mechanisms of the multifunctional effects of cyanidin on regulating antioxidant enzymes and oxidative stress-induced hepatotoxicity. The data indicated that cyanidin-mediated antioxidant enzyme expression involved the extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) pathways and Nrf2 activation. Furthermore, the synergistic effect of cyanidin and the PPAR agonist, troglitazone, on Nrf2-PPAR activation, was also observed. Besides, treatment of cyanidin and troglitazone abolished H 2O 2-induced downregulation of genes involved in lipid metabolism. In addition, H 2O 2-mediated cytotoxicity, which was caused by inducing ROS formation and apoptotic cell death, was also ameliorated upon cyanidin and troglitazone stimulation. In conclusion, mitogen-activated protein kinases (MAPKs) and the transcription factor Nrf2 played regulatory roles in cyanidin-mediated antioxidant enzyme activation. Furthermore, the combination of cyanidin and troglitazone activated PPARγ-Nrf2 and improved H 2O 2-mediated perturbation of genes involved in lipid metabolism. These data suggested that cyanidin and PPAR agonists might have synergistic benefits against metabolic dysfunction-related oxidative damage.

Original languageEnglish
Pages (from-to)2924-2933
Number of pages10
JournalJournal of Agricultural and Food Chemistry
Issue number11
Publication statusPublished - Mar 21 2012



  • anthocyanidin
  • chronic nonalcoholic fatty liver disease
  • oxidative stress
  • synergistic effect
  • thiazolidinedione

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Chemistry(all)

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