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Physalin A regulates the Nrf2 pathway through ERK and p38 for induction of detoxifying enzymes

Ji Min Shin1,2, Kyung-Mi Lee1, Hee Ju Lee3

  • 1Natural Products Research Center, Korea Institute of Science and Technology (KIST) Gangneung Institute of Natural Products, Gangneung, Gangwon-do, 25451, Republic of Korea.

BMC Complementary and Alternative Medicine
|May 11, 2019
PubMed
Abstract

Insights

Physalin A activates the Nrf2 pathway, increasing detoxifying enzyme expression. This suggests physalin A is a potential chemopreventive agent for liver diseases and cancer.

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Cancer Research

Background:

  • Physalin A, a compound from Physalis alkekengi var. franchetii, possesses known pharmacological properties.
  • The specific role of physalin A in cancer chemoprevention via the Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway remains underexplored.

Purpose of the Study:

  • To investigate the effects of physalin A on cancer chemoprevention mechanisms.
  • To elucidate the involvement of the Nrf2 pathway in physalin A's action.

Main Methods:

  • Utilized Hepa-1c1c7 and HepG2 cell lines for experiments.
  • Assessed quinone reductase (QR) activity and Nrf2 target gene transcription using reporter assays.
  • Employed real-time PCR, western blotting, and immunocytochemistry to analyze gene expression and protein localization, including Nrf2 and kinase activity.

Main Results:

  • Physalin A significantly induced QR activity, a key Nrf2-dependent enzyme.
  • Physalin A treatment increased the expression of Nrf2 and its downstream target genes in HepG2 cells.
  • Activation of Nrf2 by physalin A was found to be regulated by ERK and p38 kinases.

Conclusions:

  • Physalin A enhances the expression of detoxifying enzymes through the activation of the Nrf2 pathway.
  • These findings indicate physalin A's potential as a chemopreventive agent for liver diseases and cancer.
Keywords:
Cancer chemopreventionExtracellular signal-regulated kinaseNF-E2-related factor 2Physalin AQuinone reductasep38 mitogen-activated protein kinase

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