Baicalein modulates Nrf2/Keap1 system in both Keap1-dependent and Keap1-independent mechanisms

Si Qin, Fangming Deng, Weiguo Wu, Liwen Jiang, Takaaki Yamashiro, Satoshi Yano, De Xing Hou*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

Baicalein, a major component of Scutellaria baicalensis Georgi (Huang Qin), is widely used in the traditional Chinese medicine. However, the mechanisms underlying cancer chemoprevention are still not clear. The present study aimed to clarify how baicalein modulate Nrf2/Keap1 system to exert its cytoprotection and cancer chemoprevention. In the upstream cellular signaling, baicalein stimulated the phosphorylation of MEK1/2, AKT and JNK1/2, which were demonstrated to be essential for baicalein-induced Nrf2 expression by their inhibitors. Immunoprecipitation with Nrf2 found that baicalein increased the amount of phosphorylated MEK1/2, AKT and JNK1/2 bound to Nrf2, and also stabilized Nrf2 protein by inhibiting the ubiquitination and proteasomal turnover of Nrf2. Simultaneously, baicalein down-regulated Keap1 by stimulating modification and degradation of Keap1 without affecting the dissociation of Keap1-Nrf2. Silencing Nrf2 using Nrf2 siRNA markedly reduced the ARE activity under both baseline and baicalein-induced conditions. Thus, baicalein positively modulate Nrf2/Keap1 system through both Keap1-independent and -dependent pathways. These finding provide an insight to understand the mechanisms of baicalein in cytoprotection and cancer chemoprevention.

Original languageEnglish
Pages (from-to)53-61
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume559
DOIs
Publication statusPublished - 2014 Oct 1
Externally publishedYes

Keywords

  • Baicalein
  • Keap1 modification
  • Nrf2 ubiquitination
  • Nrf2/Keap1 system

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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