title: Cardioprotective effects of Notoginsenoside R1 against ischemia/reperfusion injuries by regulating oxidative stress- and endoplasmic reticulum stress- related signaling pathways.
abstract: BACKGROUND
  Recent reports suggested the involvement of oxidative stress- and endoplasmic reticulum stress (ERS)-associated pathways in the progression of ischemia/reperfusion (I/R) injury. Notoginsenoside R1 (NGR1) is a novel saponin isolated from P. notoginseng, which has a history of prevention and treatment of cardiovascular diseases.
  
  
  OBJECTIVE
  We aimed to examine the cardioprotective effects of NGR1 on I/R-induced heart dysfunction ex vivo and in vitro.
  
  
  METHODS
  H9c2 cadiomyocytes were incubated with NGR1 for 24 h and exposed to hypoxia/reoxygenation. Isolated rat hearts were perfused by NGR1 for 15 min and then subjected to global ischemia/reperfusion. Hemodynamic parameters were monitored as left ventricular systolic pressure (LVSP), heart rate, and maximal rate of increase and decrease of left ventricular pressure (± dP/dt max/min).
  
  
  RESULTS
  NGR1 pretreatment prevents cell apoptosis and delays the onset of ERS by decreasing the protein expression levels of ERS-responsive proteins GRP78, P-PERK, ATF6, IRE, and inhibiting the expression of pro-apoptosis proteins CHOP, Caspase-12, and P-JNK. Besides, NGR1 scavenges free radical, and increases the activity of antioxidase. NGR1 inhibits Tunicamycin-induced cell death and cardiac dysfunction.
  
  
  CONCLUSIONS
  We elucidated the significant cardioprotective effects of NGR1 against I/R injuries, and demonstrated the involvement of oxidative stress and ERS in the protective effects of NGR1.
authors.affiliation: Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100193, China.|Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, China.|Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, China.
authors.forename: Yingli
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100193, China.|Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, China.|Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, China.
authors.forename: Guibo
authors.initials: G
authors.lastname: Sun
authors.affiliation: Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100193, China.|Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, China.|Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100193, China.|Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, China.|Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100193, China.|Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, China.|Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, China.
authors.forename: Rongchang
authors.initials: R
authors.lastname: Chen
authors.affiliation: Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100193, China.|Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, China.|Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100193, China.|Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, China.|Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, China.
authors.forename: Qidi
authors.initials: Q
authors.lastname: Ai
authors.affiliation: Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Harbin, 150040, China.
authors.forename: Na
authors.initials: N
authors.lastname: Xing
authors.affiliation: Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100193, China.|Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, China.|Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D036145:Ginsenosides / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D036145:Ginsenosides; C072936:notoginsenoside R1