Sinomenine Confers Protection Against Myocardial Ischemia Reperfusion Injury by Preventing Oxidative Stress, Cellular Apoptosis, and Inflammation
Sinomenine (SIN), an alkaloid extracted from the root of S. acutum. sinomenine, has been shown to have antiarrhythmic, antioxidant, and anti-inflammatory effects in myocardial ischemia-reperfusion injury (MIRI) ex vivo. In this study, we investigated the cardioprotective effects of SIN in an in vivo...
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.922484/full |
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| author | Boyu Xia Qi Li Jingjing Wu Xiaomei Yuan Fei Wang Xu Lu Chao Huang Koulong Zheng Rongrong Yang Le Yin Kun Liu Qingsheng You |
| author_facet | Boyu Xia Qi Li Jingjing Wu Xiaomei Yuan Fei Wang Xu Lu Chao Huang Koulong Zheng Rongrong Yang Le Yin Kun Liu Qingsheng You |
| author_sort | Boyu Xia |
| collection | DOAJ |
| description | Sinomenine (SIN), an alkaloid extracted from the root of S. acutum. sinomenine, has been shown to have antiarrhythmic, antioxidant, and anti-inflammatory effects in myocardial ischemia-reperfusion injury (MIRI) ex vivo. In this study, we investigated the cardioprotective effects of SIN in an in vivo mouse model of MIRI. Adult male C57BL/6J mice received SIN (80 mg/kg) for 5 days and underwent 30 min of percutaneous occlusion of the left anterior descending artery (LAD) followed by 24 h of reperfusion. Results showed that pretreatment with SIN significantly reduced myocardial infarct size and concentrations of markers of cardiac injury and improved left ventricular ejection fraction (EF) and shortening fraction (FS) in MIRI mice. The SIN pretreatment prevented the MIRI-induced decrease in the expression levels of Bcl-2, increase in the expression levels of caspase-3, caspase-9, and Bax, and increase in the number of TUNEL-positive cells in ischemic heart tissue. It was also found that pretreatment with SIN prevented the MIRI-induced oxidative stress imbalance in ischemic heart tissue, as shown by the increase in total antioxidant capacity (T-AOC) and glutathione (GSH) and the decrease in malondialdehyde (MDA), reactive oxygen species (ROS), and dihydroethidium (DHE) density. Further studies showed that the stimulus of cardiac ischemia/reperfusion caused a remarkable increase in the expression levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) mRNA in ischemic heart tissue, which was effectively prevented by pretreatment with SIN. These results demonstrate that SIN can attenuate MIRI-induced cardiac injury in vivo by preventing oxidative stress, inflammation, and apoptosis. |
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| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-12T12:20:25Z |
| publishDate | 2022-06-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-cc6a44071a2a4b7390f5df0796b296a52022-12-22T03:33:19ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-06-011310.3389/fphar.2022.922484922484Sinomenine Confers Protection Against Myocardial Ischemia Reperfusion Injury by Preventing Oxidative Stress, Cellular Apoptosis, and InflammationBoyu Xia0Qi Li1Jingjing Wu2Xiaomei Yuan3Fei Wang4Xu Lu5Chao Huang6Koulong Zheng7Rongrong Yang8Le Yin9Kun Liu10Qingsheng You11Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, ChinaDepartment of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, ChinaDepartment of Cardiology, Suzhou Kowloon Hospital of Shanghai Jiaotong University School of Medicine, Suzhou, ChinaDepartment of Cardiology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, ChinaDepartment of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, ChinaDepartment of Pharmacology, School of Pharmacy, Nantong University, Nantong, ChinaDepartment of Pharmacology, School of Pharmacy, Nantong University, Nantong, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Nantong University, Nantong, ChinaDepartment of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, ChinaDepartment of Cardiology, Tongzhou People’s Hospital, Nantong, ChinaDepartment of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, ChinaDepartment of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, ChinaSinomenine (SIN), an alkaloid extracted from the root of S. acutum. sinomenine, has been shown to have antiarrhythmic, antioxidant, and anti-inflammatory effects in myocardial ischemia-reperfusion injury (MIRI) ex vivo. In this study, we investigated the cardioprotective effects of SIN in an in vivo mouse model of MIRI. Adult male C57BL/6J mice received SIN (80 mg/kg) for 5 days and underwent 30 min of percutaneous occlusion of the left anterior descending artery (LAD) followed by 24 h of reperfusion. Results showed that pretreatment with SIN significantly reduced myocardial infarct size and concentrations of markers of cardiac injury and improved left ventricular ejection fraction (EF) and shortening fraction (FS) in MIRI mice. The SIN pretreatment prevented the MIRI-induced decrease in the expression levels of Bcl-2, increase in the expression levels of caspase-3, caspase-9, and Bax, and increase in the number of TUNEL-positive cells in ischemic heart tissue. It was also found that pretreatment with SIN prevented the MIRI-induced oxidative stress imbalance in ischemic heart tissue, as shown by the increase in total antioxidant capacity (T-AOC) and glutathione (GSH) and the decrease in malondialdehyde (MDA), reactive oxygen species (ROS), and dihydroethidium (DHE) density. Further studies showed that the stimulus of cardiac ischemia/reperfusion caused a remarkable increase in the expression levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) mRNA in ischemic heart tissue, which was effectively prevented by pretreatment with SIN. These results demonstrate that SIN can attenuate MIRI-induced cardiac injury in vivo by preventing oxidative stress, inflammation, and apoptosis.https://www.frontiersin.org/articles/10.3389/fphar.2022.922484/fullsinomenineischemia reperfusion injuryoxidative stressinflammationapoptosis |
| spellingShingle | Boyu Xia Qi Li Jingjing Wu Xiaomei Yuan Fei Wang Xu Lu Chao Huang Koulong Zheng Rongrong Yang Le Yin Kun Liu Qingsheng You Sinomenine Confers Protection Against Myocardial Ischemia Reperfusion Injury by Preventing Oxidative Stress, Cellular Apoptosis, and Inflammation Frontiers in Pharmacology sinomenine ischemia reperfusion injury oxidative stress inflammation apoptosis |
| title | Sinomenine Confers Protection Against Myocardial Ischemia Reperfusion Injury by Preventing Oxidative Stress, Cellular Apoptosis, and Inflammation |
| title_full | Sinomenine Confers Protection Against Myocardial Ischemia Reperfusion Injury by Preventing Oxidative Stress, Cellular Apoptosis, and Inflammation |
| title_fullStr | Sinomenine Confers Protection Against Myocardial Ischemia Reperfusion Injury by Preventing Oxidative Stress, Cellular Apoptosis, and Inflammation |
| title_full_unstemmed | Sinomenine Confers Protection Against Myocardial Ischemia Reperfusion Injury by Preventing Oxidative Stress, Cellular Apoptosis, and Inflammation |
| title_short | Sinomenine Confers Protection Against Myocardial Ischemia Reperfusion Injury by Preventing Oxidative Stress, Cellular Apoptosis, and Inflammation |
| title_sort | sinomenine confers protection against myocardial ischemia reperfusion injury by preventing oxidative stress cellular apoptosis and inflammation |
| topic | sinomenine ischemia reperfusion injury oxidative stress inflammation apoptosis |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.922484/full |
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