title: The effects of ginsenoside Rb1 on JNK in oxidative injury in cardiomyocytes.
abstract: Reactive oxygen species (ROS) can induce oxidative injury via iron interactions (i.e. Fenton chemistry and hydroxyl radical formation). Our prior work suggested that American ginseng berry extract and ginsenoside Re were highly cardioprotective against oxidant stress. To extend this study, we evaluated the protective effect of protopanaxadiol-type ginsenoside Rb1 (gRb1) on H(2)O(2)-induced oxidative injury in cardiomyocytes and explored the ROS-mediated intracellular signaling mechanism. Cultured embryonic chick cardiomyocytes (4-5 day) were used. Cell death was assessed by propidium iodide and lactate dehydrogenase release. Pretreatment with gRb1 (0.01, 0.1, or 1 μM) for 2 h and concurrent treatment with H(2)O(2) (0.5 mM) for 2 h resulted in a dose-dependent reduction of cell death, 36.6 ± 2.9% (n = 12, p < 0.05), 30.5 ± 5.1% (n = 12, p < 0.05) and 28.6 ± 3.1% (n = 12, p < 0.01) respectively, compared to H(2)O(2)-exposed cells (48.2 ± 3.3%, n = 12). This cardioprotective effect of gRb1 was associated with attenuated intracellular ROS generation as measured by 6-carboxy-2', 7'-dichlorodihydrofluorescein diacetate, preserved the mitochondrial membrane potential as determined using JC-1. In the ESR study, gRb1 exhibited the scavenging DPPH and hydroxyl radical activities. Furthermore, our data showed the increased JNK phosphorylation (p-JNK) in H(2)O(2)-exposed cells was suppressed by the pretreatment with gRb 1 (1 μM) (p < 0.01). Co-treatment of gRb1 with a specific inhibitor of JNK SP600125 (10 μM) further reduced the p-JNK and enhanced the cell survival after H(2)O(2) exposure. Collectively, our results suggest that gRb1 conferred cardioprotection that was mediated via attenuating ROS and suppressing ROS-induced JNK activation.
authors.affiliation: Department of Emergency Medicine, University of Illinois Hospital & Health Sciences System, Chicago, IL 60612, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Zuo-Hui
authors.initials: ZH
authors.lastname: Shao
authors.forename: Jing-Tian
authors.initials: JT
authors.lastname: Xie
authors.forename: Chong-Zhi
authors.initials: CZ
authors.lastname: Wang
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Ramachandran
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Yin
authors.forename: Han
authors.initials: H
authors.lastname: Aung
authors.forename: Chang-Qing
authors.initials: CQ
authors.lastname: Li
authors.forename: Gina
authors.initials: G
authors.lastname: Qin
authors.forename: Terry
authors.initials: T
authors.lastname: Vanden Hoek
authors.forename: Chun-Su
authors.initials: CS
authors.lastname: Yuan
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D019610:Cytoprotection; D004578:Electron Spin Resonance Spectroscopy; D004789:Enzyme Activation; D016166:Free Radical Scavengers / Q000494:pharmacology*; D036145:Ginsenosides / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000633:toxicity; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000873:Anthracenes; D016166:Free Radical Scavengers; D036145:Ginsenosides; D016877:Oxidants; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; C432165:pyrazolanthrone; C442759:ginsenoside Rb1; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D048031:JNK Mitogen-Activated Protein Kinases