title: Cytoprotection of baicalein against oxidative stress-induced cardiomyocytes injury through the Nrf2/Keap1 pathway.
abstract: Baicalein is one of the major flavonoids found in the root of Scutellaria baicalensis Georgi. Previous studies suggest that baicalein displays protective effect on experimental cardiac models in vitro and in vivo. However, the mode of action remains unclear. Here, we showed that baicalein conferred cardioprotective effect against oxidative stress-induced cell injury in H9c2 cells and human embryonic stem cells-derived cardiomyocytes. Immunoprecipitation with anti-NF-E2-related factor 2 (Nrf2) antibody in baicalein-treated cells demonstrated that baicalein effectively disrupted the association between Nrf2 and Kelch-like epichlorohydrin-associated protein 1 (Keap1). In addition, the unbounded Nrf2 translocated from cytoplasm to nucleus and increased Nrf2/heme oxygenase-1 (HO-1) content in a time-dependent manner. Moreover, antioxidant response element transcriptional activity was enhanced by baicalein treatment, and the Nrf2 siRNA transfection could block the cytoprotective effect of baicalein. Taken together, these results demonstrate that baicalein protected cardiomyocytes against oxidative stress-induced cell injury through the Nrf2/Keap1 pathway.
authors.affiliation: *State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China; †Department of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai, China; ‡Stem Cell and Regenerative Medicine Consortium, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China; and §Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.
authors.forename: Guozhen
authors.initials: G
authors.lastname: Cui
authors.forename: Sharon Chui Wah
authors.initials: SC
authors.lastname: Luk
authors.forename: Ronald Adolphus
authors.initials: RA
authors.lastname: Li
authors.forename: Ken Kwok Keung
authors.initials: KK
authors.lastname: Chan
authors.forename: Si Wan
authors.initials: SW
authors.lastname: Lei
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Huifang
authors.initials: H
authors.lastname: Shen
authors.forename: George Pak Heng
authors.initials: GP
authors.lastname: Leung
authors.forename: Simon Ming Yuen
authors.initials: SM
authors.lastname: Lee
mesh_terms: D000818:Animals; D061745:Antioxidant Response Elements / Q000235:genetics; D002460:Cell Line; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects*; D044950:Flavanones / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D000072019:Kelch-Like ECH-Associated Protein 1; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D013997:Time Factors
chemical_list: D044950:Flavanones; D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; D034741:RNA, Small Interfering; C006680:baicalein; D051547:Heme Oxygenase-1