Identification of baicalein as a ferroptosis inhibitor by natural product library screening

Yangchun Xie, Xinxin Song, Xiaofang Sun, Jin Huang, Meizuo Zhong, Michael T. Lotze, Herbert J. Zeh, Rui Kang, Daolin Tang

Research output: Contribution to journalArticlepeer-review

144 Scopus citations


Ferroptosis, a novel form of regulated cell death, is characterized by oxidative injury from iron accumulation and lipid peroxidation. In a natural product library screening for ferroptosis inhibitor, we found that baicalein is a potent inhibitor of erastin-induced ferroptosis in pancreatic cancer cells. Baicalein (also termed 5,6,7-trihydroxyflavone) is a flavonoid originally obtained from the roots of Scutellaria baicalensis and Scutellaria lateriflora. We showed that baicalein exhibits remarkable anti-ferroptosis activity compared with well-known ferroptosis inhibitors such as ferrostatin-1, liproxstatin-1, deferoxamine mesylate, and β-mercaptoethanol. At the biochemistry level, baicalein limits erastin-induced ferrous iron production, glutathione depletion, and lipid peroxidation. At the protein level, baicalein suppresses erastin-mediated degradation of glutathione peroxidase 4, a phospholipid hydroperoxidase that protects cells against membrane lipid peroxidation. Thus, baicalein enhances cellular anti-ferroptosis capacity and could be a potential therapeutic agent for ferroptosis-associated tissue injury.

Original languageEnglish (US)
Pages (from-to)775-780
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number4
StatePublished - May 13 2016
Externally publishedYes


  • Baicalein
  • Ferroptosis
  • GPX4
  • Lipid peroxidation
  • Natural product

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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