The role of Nrf2 in astragaloside IV-mediated antioxidative protection on heart failure
العنوان: | The role of Nrf2 in astragaloside IV-mediated antioxidative protection on heart failure |
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المؤلفون: | Yu-Kun Ren, Li Liu, Kui-Kui Zhang, Yan Liu, Yan-Bo Sui |
المصدر: | Pharmaceutical Biology, Vol 58, Iss 1, Pp 1201-1207 (2020) Pharmaceutical Biology article-version (VoR) Version of Record |
بيانات النشر: | Taylor & Francis Group, 2020. |
سنة النشر: | 2020 |
مصطلحات موضوعية: | Male, Cardiotonic Agents, NF-E2-Related Factor 2, Myocardial Infarction, Pharmaceutical Science, RM1-950, Pharmacology, medicine.disease_cause, 030226 pharmacology & pharmacy, 01 natural sciences, Antioxidants, Cell Line, Rats, Sprague-Dawley, 03 medical and health sciences, Astragaloside IV, 0302 clinical medicine, Drug Discovery, mental disorders, medicine, Animals, oxidative stress, transcriptional activation, Myocytes, Cardiac, keap-1, Heart Failure, Mechanism (biology), business.industry, Stroke Volume, General Medicine, Saponins, medicine.disease, Survival Analysis, Triterpenes, Rats, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, Complementary and alternative medicine, Echocardiography, Heart failure, ho-1, Molecular Medicine, Therapeutics. Pharmacology, business, Heme Oxygenase-1, Oxidative stress, Signal Transduction, Research Article |
الوصف: | Context Heart failure is one of the most serious diseases worldwide. Astragaloside IV (ASI) is widely used in the treatment of cardiovascular diseases. Objective To elucidate the antioxidative mechanism of ASI in a rat model of left coronary artery ligation. Materials and methods Left coronary artery of Sprague–Dawley rats was ligated to establish the model of heart failure, and then vehicle (saline) or ASI (1 mg/kg/day) was orally administered to the rats (n = 15) for 6 weeks. Echocardiography was used to evaluate the cardiac function. Myocardial infarct size was measured by triphenyltetrazolium chloride staining. Oxidative stress in the ventricular myocardium was determined. Molecular mechanisms were investigated by Western blot and chromatin immunoprecipitation. Results ASI improved the cardiac function, especially ejection fraction (75.27 ± 5.75% vs. 36.26 ± 4.14%) and fractional shortening (45.39 ± 3.66% vs. 17.88 ± 1.32%), and reduced the infarct size of left ventricle (20.69 ± 2.98% vs. 39.11 ± 3.97%). ASI maintained the levels of glutathione, catalase and superoxide dismutase and prevented the leakage of creatine kinase. In addition, ASI induced the protein expression of Nrf2 (1.97-fold) and HO-1 (2.79-fold), while reduced that of Keap-1 (0.77-fold) in the ventricular myocardium. In H9c2 cells, a rat cardiomyocyte cell line, ASI induced the translocation of Nrf2 from cytoplasm to nucleus, followed by transcriptional activation of NQO-1 (8.27-fold), SOD-2 (3.27-fold) and Txn-1 (9.83-fold) genes. Discussion and conclusions ASI prevented heart failure by counteracting oxidative stress through the Nrf2/HO-1 pathway. Application in clinical practice warrants further investigation. |
اللغة: | English |
تدمد: | 1744-5116 1388-0209 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1dbccb9e71e352259d6314fb580e6c40 https://doaj.org/article/f640f2adf07542d7b83338f010f5b2d2 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....1dbccb9e71e352259d6314fb580e6c40 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 17445116 13880209 |
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