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

详细信息    查看全文

• 作者：Yangchun Xie^a ; ^b ; Xinxin Song^a ; Xiaofang Sun^c ; Jin Huang^b ; Meizuo Zhong^b ; Michael T. Lotze^a ; Herbert J. Zeh 3rd^a ; Rui Kang^a ; Daolin Tang^a ; ^c ; ^{tangd2@upmc.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Natural product ; Baicalein ; Ferroptosis ; GPX4 ; Lipid peroxidation
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2016
• 出版时间：13 May 2016
• 年：2016
• 卷：473
• 期：4
• 页码：775-780
• 全文大小：1528 K

文摘

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.