title: Natural antioxidant-isoliquiritigenin ameliorates contractile dysfunction of hypoxic cardiomyocytes via AMPK signaling pathway.
abstract: Isoliquiritigenin (ISL), a simple chalcone-type flavonoid, is derived from licorice compounds and is mainly present in foods, beverages, and tobacco. Reactive oxygen species (ROS) is a critical factor involved in modulating cardiac stress response signaling during ischemia and reperfusion. We hypothesize that ISL as a natural antioxidant may protect heart against ischemic injury via modulating cellular redox status and regulating cardioprotective signaling pathways. The fluorescent probe H2DCFDA was used to measure the level of intracellular ROS. The glucose uptake was determined by 2-deoxy-D-glucose-(3)H accumulation. The IonOptix System measured the contractile function of isolated cardiomyocytes. The results demonstrated that ISL treatment markedly ameliorated cardiomyocytes contractile dysfunction caused by hypoxia. ISL significantly stimulated cardioprotective signaling, AMP-activated protein kinase (AMPK), and extracellular signal-regulated kinase (ERK) signaling pathways. The ROS fluorescent probe H2DCFDA determination indicated that ISL significantly reduced cardiac ROS level during hypoxia/reoxygenation. Moreover, ISL reduced the mitochondrial potential (Δψ) of isolated mouse cardiomyocytes. Taken together, ISL as a natural antioxidant demonstrated the cardioprotection against ischemic injury that may attribute to the activation of AMPK and ERK signaling pathways and balance of cellular redox status.
authors.affiliation: Institute of Physiology, School of Basic Medicine Sciences, Lanzhou University, Lanzhou 730000, China ; Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo-SUNY University of New York, Buffalo, NY 14214, USA.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Zhu
authors.forename: Xiuying
authors.initials: X
authors.lastname: Zhang
authors.forename: Yina
authors.initials: Y
authors.lastname: Ma
authors.forename: Wenguang
authors.initials: W
authors.lastname: Li
authors.forename: Ji-Mei
authors.initials: JM
authors.lastname: Chen
authors.forename: Hui-Ming
authors.initials: HM
authors.lastname: Guo
authors.forename: Richard
authors.initials: R
authors.lastname: Bucala
authors.forename: Jian
authors.initials: J
authors.lastname: Zhuang
authors.forename: Ji
authors.initials: J
authors.lastname: Li
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000737:chemistry*; D002118:Calcium / Q000378:metabolism; D015687:Cell Hypoxia; D002478:Cells, Cultured; D047188:Chalcones / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury; D015398:Signal Transduction
chemical_list: D000975:Antioxidants; D047188:Chalcones; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; C040920:isoliquiritigenin; D048049:Extracellular Signal-Regulated MAP Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose; D002118:Calcium