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Chem Biodivers. 2019 Nov;16(11):e1900400. doi: 10.1002/cbdv.201900400. Epub 2019 Oct 10.

Recent Advances of Natural Polyphenols Activators for Keap1-Nrf2 Signaling Pathway.

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Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, School of Medicine of University of Electronic Science and Technology of China, No. 32 West Second Section First Ring Road, Chengdu, 610072, P. R. China.
Department of Hematology, Miller School of Medicine, University of Miami, Miami, 33136, USA.
Department of Gastrointestinal Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, 610072, P. R. China.


The Keap1-Nrf2/ARE signaling pathway is an important defense system against exogenous and endogenous oxidative stress injury. The dysregulation of the signaling pathway is associated with many diseases, such as cancer, diabetes, and respiratory diseases. Over the years, a wide range of natural products has provided sufficient resources for the discovery of potential therapeutic drugs. Among them, polyphenols possess Nrf2 activation, not only inhibit the production of ROS, inhibit Keap1-Nrf2 protein-protein interaction, but also degrade Keap1 and regulate the Nrf2 related pathway. In fact, with the continuous improvement of natural polyphenols separation and purification technology and further studies on the Keap1-Nrf2 molecular mechanism, more and more natural polyphenols monomer components of Nrf2 activators have been gradually discovered. In this view, we summarize the research status of natural polyphenols that have been found with apparent Nrf2 activation and their action modes. On the whole, this review may guide the design of novel Keap1-Nrf2 activator.


Keap1-Nrf2 signaling pathway; activators; diseases; natural polyphenols


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