Frontiers in Pharmacology (Nov 2017)
Calenduloside E Analogues Protecting H9c2 Cardiomyocytes Against H2O2-Induced Apoptosis: Design, Synthesis and Biological Evaluation
- Yu Tian,
- Yu Tian,
- Yu Tian,
- Yu Tian,
- Yu Tian,
- Yu-Yang Du,
- Yu-Yang Du,
- Yu-Yang Du,
- Yu-Yang Du,
- Yu-Yang Du,
- Hai Shang,
- Hai Shang,
- Hai Shang,
- Hai Shang,
- Hai Shang,
- Min Wang,
- Min Wang,
- Min Wang,
- Min Wang,
- Min Wang,
- Zhong-Hao Sun,
- Zhong-Hao Sun,
- Zhong-Hao Sun,
- Zhong-Hao Sun,
- Zhong-Hao Sun,
- Bao-Qi Wang,
- Bao-Qi Wang,
- Bao-Qi Wang,
- Bao-Qi Wang,
- Bao-Qi Wang,
- Bao-Qi Wang,
- Di Deng,
- Di Deng,
- Di Deng,
- Di Deng,
- Di Deng,
- Di Deng,
- Shan Wang,
- Shan Wang,
- Shan Wang,
- Shan Wang,
- Shan Wang,
- Xu-Dong Xu,
- Xu-Dong Xu,
- Xu-Dong Xu,
- Xu-Dong Xu,
- Xu-Dong Xu,
- Gui-Bo Sun,
- Gui-Bo Sun,
- Gui-Bo Sun,
- Gui-Bo Sun,
- Gui-Bo Sun,
- Xiao-Bo Sun,
- Xiao-Bo Sun,
- Xiao-Bo Sun,
- Xiao-Bo Sun,
- Xiao-Bo Sun
Affiliations
- Yu Tian
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Yu Tian
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Yu Tian
- Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Yu Tian
- Zhong Guan Cun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Yu Tian
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Yu-Yang Du
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Yu-Yang Du
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Yu-Yang Du
- Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Yu-Yang Du
- Zhong Guan Cun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Yu-Yang Du
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Hai Shang
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Hai Shang
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Hai Shang
- Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Hai Shang
- Zhong Guan Cun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Hai Shang
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Min Wang
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Min Wang
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Min Wang
- Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Min Wang
- Zhong Guan Cun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Min Wang
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Zhong-Hao Sun
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Zhong-Hao Sun
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Zhong-Hao Sun
- Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Zhong-Hao Sun
- Zhong Guan Cun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Zhong-Hao Sun
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Bao-Qi Wang
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Bao-Qi Wang
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Bao-Qi Wang
- Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Bao-Qi Wang
- Zhong Guan Cun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Bao-Qi Wang
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Bao-Qi Wang
- Center of Research and Development on Life Sciences and Environment Sciences, Harbin University of Commerce, Harbin, China
- Di Deng
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Di Deng
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Di Deng
- Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Di Deng
- Zhong Guan Cun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Di Deng
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Di Deng
- Center of Research and Development on Life Sciences and Environment Sciences, Harbin University of Commerce, Harbin, China
- Shan Wang
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Shan Wang
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Shan Wang
- Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Shan Wang
- Zhong Guan Cun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Shan Wang
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Xu-Dong Xu
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Xu-Dong Xu
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Xu-Dong Xu
- Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Xu-Dong Xu
- Zhong Guan Cun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Xu-Dong Xu
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Gui-Bo Sun
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Gui-Bo Sun
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Gui-Bo Sun
- Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Gui-Bo Sun
- Zhong Guan Cun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Gui-Bo Sun
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Xiao-Bo Sun
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Xiao-Bo Sun
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Xiao-Bo Sun
- Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Xiao-Bo Sun
- Zhong Guan Cun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Xiao-Bo Sun
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- DOI
- https://doi.org/10.3389/fphar.2017.00862
- Journal volume & issue
-
Vol. 8
Abstract
Modulation of apoptosis is therapeutically effective in cardiomyocytes damage. Calenduloside E (CE), a naturally occurring triterpenoid saponin, is a potent anti-apoptotic agent. However, little is known about its synthetic analogues on the protective effects in apoptosis of cardiomyocytes. The present research was performed to investigate the potential protective effect of CE analogues against H2O2-induced apoptosis in H9c2 cardiomyocytes and the underlying mechanisms. Sixteen novel CE anologues have been designed, synthesized and biological evaluation. Among the 16 CE anologues, as well as the positive control CE tested, compound 5d was the most effective in improving cardiomyocytes viability. Pretreatment with anologue 5d inhibited ROS generation, maintained the mitochondrial membrane potential and reduced apoptotic cardiomyocytes. Moreover, exposure to H2O2 significantly increased the levels of Bax, cleaved caspase-3, and cleaved PARP, and decreased the level of Bcl-2, resulting in cell apoptosis. Pretreatment with anologue 5d (0.02–0.5 μg/mL) dose-dependently upregulated antiapoptotic proteins and downregulated proapoptotic proteins mentioned above during H2O2-induced apoptosis. These results suggested that CE analogues provide protection to H9c2 cardiomyocytes against H2O2-induced oxidative stress and apoptosis, most likely via anti-apoptotic mechanism, and provided the basis for the further optimization of the CE analogues.
Keywords
- Calenduloside E (CE) analogues
- triterpenoid saponin
- cardiomyocytes
- apoptosis
- ROS
- anti-apoptotic mechanism
