title: Salvianolic Acid A Protects H9c2 Cells from Arsenic Trioxide-Induced Injury via Inhibition of the MAPK Signaling Pathway.
abstract: OBJECTIVE
  This study aimed to investigate whether Salvianolic acid A (Sal A) conferred cardiac protection against Arsenic trioxide (ATO)-induced cardiotoxicity in H9c2 cells by inhibiting MAPK pathways activation.
  
  
  METHODS
  H9c2 cardiac cells were exposed to 10 µM ATO for 24 h to induce cytotoxicity. The cells were pretreated with Sal A for 4 h before exposure to ATO. Cell viability was determined utilizing the MTT assay. The percentage of apoptosis was measured by a FITC-Annexin V/PI apoptosis kit for flow cytometry. Mitochondrial membrane potential (∆Ψm) was detected by JC-1. The intracellular ROS levels were measured using an Image-iTTM LIVE Green Reactive Oxygen Species Detection Kit. The apoptosis-related proteins and the MAPK signaling pathways proteins expression were quantified by Western blotting.
  
  
  RESULTS
  Sal A pretreatment increased cell viability, suppressed ATO-induced mitochondrial membrane depolarization, and significantly altered the apoptotic rate by enhancing endogenous antioxidative enzyme activity and ROS generation. Signal transduction studies indicated that Sal A suppressed the ATO-induced activation of the MAPK pathway. More importantly, JNK, ERK, and p38 inhibitors mimicked the cytoprotective activity of Sal A against ATO-induced injury in H9c2 cells by increasing cell viability, up-regulating Bcl-2 protein expression, and down-regulating both Bax and caspase-3 protein expression.
  
  
  CONCLUSIONS
  Sal A decreases the ATO-induced apoptosis and necrosis of H9c2 cells, and the underlying mechanisms of this protective effect of Sal A may be connected with the MAPK pathways.
authors.affiliation: Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.|Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, China.|Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, China.|Key Laboratory of efficacy evaluation of Chinese Medicine against glyeolipid metabolism disorder disease, State Administration of Traditional Chinese Medicine, Beijing, China.
authors.forename: Jing-Yi
authors.initials: JY
authors.lastname: Zhang
authors.affiliation: Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.|Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, China.|Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, China.|Key Laboratory of efficacy evaluation of Chinese Medicine against glyeolipid metabolism disorder disease, State Administration of Traditional Chinese Medicine, Beijing, China.
authors.forename: Gui-Bo
authors.initials: GB
authors.lastname: Sun
authors.affiliation: Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.|Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, China.|Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, China.|Key Laboratory of efficacy evaluation of Chinese Medicine against glyeolipid metabolism disorder disease, State Administration of Traditional Chinese Medicine, Beijing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.|Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, China.|Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, China.|Key Laboratory of efficacy evaluation of Chinese Medicine against glyeolipid metabolism disorder disease, State Administration of Traditional Chinese Medicine, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.|Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, China.|Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, China.|Key Laboratory of efficacy evaluation of Chinese Medicine against glyeolipid metabolism disorder disease, State Administration of Traditional Chinese Medicine, Beijing, China.
authors.forename: Yu-Yang
authors.initials: YY
authors.lastname: Du
authors.affiliation: Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.|Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, China.|Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, China.|Key Laboratory of efficacy evaluation of Chinese Medicine against glyeolipid metabolism disorder disease, State Administration of Traditional Chinese Medicine, Beijing, China.
authors.forename: Ying-Li
authors.initials: YL
authors.lastname: Yu
authors.affiliation: Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.|Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, China.|Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, China.|Key Laboratory of efficacy evaluation of Chinese Medicine against glyeolipid metabolism disorder disease, State Administration of Traditional Chinese Medicine, Beijing, China.
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals; D002109:Caffeic Acids; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007773:Lactates; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009336:Necrosis; D010087:Oxides / Q000633:toxicity*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D001152:Arsenicals; C000617196:Bcl2 protein, rat; D002109:Caffeic Acids; D002316:Cardiotonic Agents; D007773:Lactates; D010087:Oxides; D019253:Proto-Oncogene Proteins c-bcl-2; C066201:salvianolic acid A; D048049:Extracellular Signal-Regulated MAP Kinases; D000077237:Arsenic Trioxide
keywords: Apoptosis; Arsenic trioxide; Cardiotoxicity; MAPK; Oxidative stress; Salvianolic acid A