Nrf2 activation by SK-119 attenuates oxidative stress, UVB, and LPS-Induced damage

Shirin Kahremany, Ilana Babaev, Raanan Gvirtz, Navit Ogen-Stern, Salome Azoulay-Ginsburg, Hanoch Senderowitz, Guy Cohen, Arie Gruzman

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Background/Aims: The Nrf2 signaling pathway plays a pivotal role in neutralizing excess reactive oxygen species formation and therefore enhancing the endogenous cellular protection mechanism. Thus, activating this pathway may provide therapeutic options against oxidative stress-related disorders. We have recently applied a computer-aided drug design approach to the design and synthesis of novel Nrf2 enhancers. The current study was aimed at investigating the potential beneficial impact of (E)-5-oxo-1-(4-((2,4,6-trihydroxybenzylidene)amino)phenyl)pyrrolidine-3-carboxylic acid (SK-119) in skin oxidative damage models. Methods: SK-119, tested initially in PC-12 cells, attenuated oxidative stress-induced cytotoxicity concomitantly with Nrf2 activation. The potential impact of this compound was evaluated in skin-based disease models both in vitro (HaCaT cells) and ex vivo (human skin organ culture). Results: The data clearly showed the marked anti-inflammatory and photoprotection properties of the compound; SK-119-treated cells or tissues displayed a reduction in cytokine secretion induced by lipopolysaccharides (LPS) in a manner comparable with dexamethasone. In addition, topical application of SK-119 was able to block UVB-induced oxidative stress and attenuated caspase-mediated apoptosis, DNA adduct formation, and the concomitant cellular damage. Conclusion: These results indicate that SK-119 is an Nrf2 activator that can be used as a prototype molecule for the development of novel treatments of dermatological disorders related to oxidative stress.

Original languageEnglish
Pages (from-to)173-181
Number of pages9
JournalSkin Pharmacology and Physiology
Issue number4
StatePublished - 1 Jul 2019

Bibliographical note

Publisher Copyright:
© 2019 S. Karger AG, Basel.


  • LPS-induced damage
  • Nrf2 activator
  • SK-119
  • UVB


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