Cardiac Protection of a Novel Lupane-Type Triterpenoid from Injuries Induced by Hypoxia–Reperfusion
Myocardial ischemia–reperfusion injury (MIRI) leads to cardiac remodeling and heart failure associated with acute myocardial infarction, which is one of the leading causes of death worldwide. Betulinic acid (BA), a widely distributed lupane-type triterpenoid, has been reported to possess antioxidati...
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| Format: | Article |
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MDPI AG
2022-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/16/9473 |
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| author | Beibei Guo Jiaxin Cao Yi Liu Yuhang Wang Yi Qian Guangtong Chen Weizhong Zhu |
| author_facet | Beibei Guo Jiaxin Cao Yi Liu Yuhang Wang Yi Qian Guangtong Chen Weizhong Zhu |
| author_sort | Beibei Guo |
| collection | DOAJ |
| description | Myocardial ischemia–reperfusion injury (MIRI) leads to cardiac remodeling and heart failure associated with acute myocardial infarction, which is one of the leading causes of death worldwide. Betulinic acid (BA), a widely distributed lupane-type triterpenoid, has been reported to possess antioxidative activity and inhibit apoptosis in MIRI. Due to the low bioavailability and water insolubility of BA, a previous study found a series of BA-derivative compounds by microbial transformation. In this study, we observe whether there are anti-MIRI effects of BTA07, a BA derivative, on cardiac injuries induced by hypoxia/reoxygenation (H/R) in adult rat cardiomyocytes in vitro and in Langendorff-perfused hearts ex vivo, and further explore its mechanism of cardioprotection to find more efficient BA derivatives. The hemodynamic parameters of isolated hearts were monitored and recorded by a Lab Chart system. The markers of oxidative stress and apoptosis in isolated hearts and adult rat cardiomyocytes (ARCMs) were evaluated. The expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X (Bax), protein kinase B (Akt) and phospho-Akt (pAkt, Ser473) induced by H/R were detected via Western blot. The Langendorff experiments showed that BTA07 improves hemodynamic parameters, reduces myocardium damage and infarct size, inhibits levels of myocardial tissue enzymes lactate dehydrogenase (LDH) and creatine kinase (CK) in the coronary outflow and reduces oxidative stress and the activation of caspase-3 in the myocardium. In vitro, BTA07 reduced cell death and caspase-3 activation and inhibited reactive oxygen species (ROS) generation. Furthermore, the protective effects of BTA07 were attenuated by inhibition of the PI3K/Akt signaling pathway with LY294002 in ARCMs. BTA07 protects ARCMs and isolated hearts from hypoxia–reperfusion partly by inhibiting oxidative stress and cardiomyocyte apoptosis. |
| first_indexed | 2024-03-09T04:18:03Z |
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| language | English |
| last_indexed | 2024-03-09T04:18:03Z |
| publishDate | 2022-08-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7cd07bb0072d43d4afab836fcb09405f2023-12-03T13:50:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012316947310.3390/ijms23169473Cardiac Protection of a Novel Lupane-Type Triterpenoid from Injuries Induced by Hypoxia–ReperfusionBeibei Guo0Jiaxin Cao1Yi Liu2Yuhang Wang3Yi Qian4Guangtong Chen5Weizhong Zhu6Department of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, ChinaDepartment of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, ChinaDepartment of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, ChinaDepartment of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, ChinaDepartment of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, ChinaDepartment of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, ChinaDepartment of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, ChinaMyocardial ischemia–reperfusion injury (MIRI) leads to cardiac remodeling and heart failure associated with acute myocardial infarction, which is one of the leading causes of death worldwide. Betulinic acid (BA), a widely distributed lupane-type triterpenoid, has been reported to possess antioxidative activity and inhibit apoptosis in MIRI. Due to the low bioavailability and water insolubility of BA, a previous study found a series of BA-derivative compounds by microbial transformation. In this study, we observe whether there are anti-MIRI effects of BTA07, a BA derivative, on cardiac injuries induced by hypoxia/reoxygenation (H/R) in adult rat cardiomyocytes in vitro and in Langendorff-perfused hearts ex vivo, and further explore its mechanism of cardioprotection to find more efficient BA derivatives. The hemodynamic parameters of isolated hearts were monitored and recorded by a Lab Chart system. The markers of oxidative stress and apoptosis in isolated hearts and adult rat cardiomyocytes (ARCMs) were evaluated. The expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X (Bax), protein kinase B (Akt) and phospho-Akt (pAkt, Ser473) induced by H/R were detected via Western blot. The Langendorff experiments showed that BTA07 improves hemodynamic parameters, reduces myocardium damage and infarct size, inhibits levels of myocardial tissue enzymes lactate dehydrogenase (LDH) and creatine kinase (CK) in the coronary outflow and reduces oxidative stress and the activation of caspase-3 in the myocardium. In vitro, BTA07 reduced cell death and caspase-3 activation and inhibited reactive oxygen species (ROS) generation. Furthermore, the protective effects of BTA07 were attenuated by inhibition of the PI3K/Akt signaling pathway with LY294002 in ARCMs. BTA07 protects ARCMs and isolated hearts from hypoxia–reperfusion partly by inhibiting oxidative stress and cardiomyocyte apoptosis.https://www.mdpi.com/1422-0067/23/16/9473triterpenoidscardiac protectionoxidative stressPI3K/Akt |
| spellingShingle | Beibei Guo Jiaxin Cao Yi Liu Yuhang Wang Yi Qian Guangtong Chen Weizhong Zhu Cardiac Protection of a Novel Lupane-Type Triterpenoid from Injuries Induced by Hypoxia–Reperfusion International Journal of Molecular Sciences triterpenoids cardiac protection oxidative stress PI3K/Akt |
| title | Cardiac Protection of a Novel Lupane-Type Triterpenoid from Injuries Induced by Hypoxia–Reperfusion |
| title_full | Cardiac Protection of a Novel Lupane-Type Triterpenoid from Injuries Induced by Hypoxia–Reperfusion |
| title_fullStr | Cardiac Protection of a Novel Lupane-Type Triterpenoid from Injuries Induced by Hypoxia–Reperfusion |
| title_full_unstemmed | Cardiac Protection of a Novel Lupane-Type Triterpenoid from Injuries Induced by Hypoxia–Reperfusion |
| title_short | Cardiac Protection of a Novel Lupane-Type Triterpenoid from Injuries Induced by Hypoxia–Reperfusion |
| title_sort | cardiac protection of a novel lupane type triterpenoid from injuries induced by hypoxia reperfusion |
| topic | triterpenoids cardiac protection oxidative stress PI3K/Akt |
| url | https://www.mdpi.com/1422-0067/23/16/9473 |
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