Qili Qiangxin,a compound herbal medicine formula,alleviates hypoxia-reoxygenation-induced apoptotic and autophagic cell death via suppression of ROS/AMPK/mTOR pathway in vitro |
| |
| Institution: | 1. Department of Cardiology, the First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510632, Guangdong Province, China;2. College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong Province, China;1. Department of Acupuncture, Baoshan Branch of Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201999, China;2. Department of Acupuncture, Baoshan Hospital of Integrated Traditional Chinese Medicine and Western Medicine, Shanghai 201999, China;1. School of Pharmacy, Faculty of Medicine and Health, the University of Sydney, Sydney, New South Wales 2006, Australia;2. The Australian Research Centre in Complementary and Integrative Medicine, School of Public Health, the University of Technology, Sydney, New South Wales 2007, Australia;3. Institute for Sustainable Futures, the University of Technology, Sydney, New South Wales 2007, Australia;4. The Woolcock Institute of Medical Research, the University of Sydney, Sydney, New South Wales 2037, Australia;5. Sydney Medical School, Faculty of Medicine and Health, the University of Sydney, Sydney, New South Wales 2006, Australia;6. Department of Respiratory & Sleep Medicine, Royal Prince Alfred Hospital, Camperdown, New South Wales 2050, Australia;1. School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan Province, China;2. Department of Rehabilitation Medicine, The Second People’s Hospital of Chengdu, Chengdu 610017, Sichuan Province, China;3. Department of Rehabilitation Medicine, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen 518107, Guangdong Province, China;4. Department of Rehabilitation Medicine, Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou 350003, Fujian Province, China;1. Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand;2. Research Institute for Human High Performance and Health Promotion (HHP & HP), Khon Kaen University, Khon Kaen 40002, Thailand;3. The PhD Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 11031, Taiwan, China;4. Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan, China;1. Department of Immunology and Hematology, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia;2. Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah 7607, Saudi Arabia;3. Clinical Nutrition Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah 7607, Saudi Arabia;4. Clinical Pathology Department, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt;1. Division of Endocrinology and Metabolism and Diabetes Centre, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636 Thessaloniki, Greece;2. Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece |
| |
| Abstract: | ObjectiveQili Qiangxin (QLQX), a compound herbal medicine formula, is used effectively to treat congestive heart failure in China. However, the molecular mechanisms of the cardioprotective effect are still unclear. This study explores the cardioprotective effect and mechanism of QLQX using the hypoxia-reoxygenation (H/R)-induced myocardial injury model.MethodsThe main chemical constituents of QLQX were analyzed using high-performance liquid chromatography-evaporative light-scattering detection. The model of H/R-induced myocardial injury in H9c2 cells was developed to simulate myocardial ischemia–reperfusion injury. Apoptosis, autophagy, and generation of reactive oxygen species (ROS) were measured to assess the protective effect of QLQX. Proteins related to autophagy, apoptosis and signalling pathways were detected using Western blotting.ResultsApoptosis, autophagy and the excessive production of ROS induced by H/R were significantly reduced after treating the H9c2 cells with QLQX. QLQX treatment at concentrations of 50 and 250 μg/mL caused significant reduction in the levels of LC3II and p62 degradation (P < 0.05), and also suppressed the AMPK/mTOR signalling pathway. Furthermore, the AMPK inhibitor Compound C (at 0.5 μmol/L), and QLQX (250 μg/mL) significantly inhibited H/R-induced autophagy and apoptosis (P < 0.01), while AICAR (an AMPK activator, at 0.5 mmol/L) increased cardiomyocyte apoptosis and autophagy and abolished the anti-apoptotic effect of QLQX. Similar phenomena were also observed on the expressions of apoptotic and autophagic proteins, demonstrating that QLQX reduced the apoptosis and autophagy in the H/R-induced injury model via inhibiting the AMPK/mTOR pathway. Moreover, ROS scavenger, N-Acetyl-L-cysteine (NAC, at 2.5 mmol/L), significantly reduced H/R-triggered cell apoptosis and autophagy (P < 0.01). Meanwhile, NAC treatment down-regulated the ratio of phosphorylation of AMPK/AMPK (P < 0.01), which showed a similar effect to QLQX.ConclusionQLQX plays a cardioprotective role by alleviating apoptotic and autophagic cell death through inhibition of the ROS/AMPK/mTOR signalling pathway. |
| |
| Keywords: | Herbal medicine Qili Qiangxin formula Hypoxia–reoxygenation Reactive oxygen species Autophagy Apoptosis AMPK/mTOR pathway |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
