title: Identification of baicalein as a ferroptosis inhibitor by natural product library screening.
abstract: 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.
authors.affiliation: The Center for DAMP Biology, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Yangchun
authors.initials: Y
authors.lastname: Xie
authors.affiliation: The Center for DAMP Biology, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Song
authors.affiliation: The Center for DAMP Biology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510510, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Meizuo
authors.initials: M
authors.lastname: Zhong
authors.affiliation: The Center for DAMP Biology, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Lotze
authors.affiliation: The Center for DAMP Biology, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors.forename: Herbert J
authors.initials: HJ
authors.lastname: Zeh
authors.affiliation: The Center for DAMP Biology, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Kang
authors.affiliation: The Center for DAMP Biology, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA; The Center for DAMP Biology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510510, China. Electronic address: tangd2@upmc.edu.
authors.forename: Daolin
authors.initials: D
authors.lastname: Tang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001665:Binding Sites; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000737:chemistry* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011485:Protein Binding
chemical_list: D005419:Flavonoids; C413305:baicilein; D007501:Iron; D005978:Glutathione
keywords: Baicalein; Ferroptosis; GPX4; Lipid peroxidation; Natural product