Aconitine promotes ROS-activated P38/MAPK/Nrf2 pathway to inhibit autophagy and promote myocardial injury
Abstract Background Aconitine has cardiotoxicity, but the mechanism of cardiotoxicity induced by aconitine is limited. The aim of this study was to investigate the mechanism of myocardial injury induced by aconitine. Methods Using aconitine, ROS inhibitor N-acetylcysteine(NAC), the autophagy activit...
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| Format: | Article |
| Language: | English |
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BMC
2024-12-01
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| Series: | Journal of Cardiothoracic Surgery |
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| Online Access: | https://doi.org/10.1186/s13019-024-03149-0 |
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| author | Chunai Yang Jinxiao Fu Fenshuang Zheng Yangshan Fu Xueqiong Duan Ruiling Zuo Junbo Zhu |
| author_facet | Chunai Yang Jinxiao Fu Fenshuang Zheng Yangshan Fu Xueqiong Duan Ruiling Zuo Junbo Zhu |
| author_sort | Chunai Yang |
| collection | DOAJ |
| description | Abstract Background Aconitine has cardiotoxicity, but the mechanism of cardiotoxicity induced by aconitine is limited. The aim of this study was to investigate the mechanism of myocardial injury induced by aconitine. Methods Using aconitine, ROS inhibitor N-acetylcysteine(NAC), the autophagy activitor Rapamycin (Rap) or the P38/MAPK pathway activitor Dehydrocorydaline treats H9C2 cells. CCK-8 assay was used to assay cell proliferation activity. Flow Cytometry was used to detect cell apoptosis. Dichloro-dihydrofluorescein diacetate was used to detect ROS levels. The expression of LC3 was detected by Immunofluorescence Staining. Western blotting detected the expression of related proteins. The mRNA levels of inflammatory factors were detected by RT-qPCR. Results Aconitine inhibits cardiomyocyte proliferation, induces apoptosis and secretion of inflammatory factors. Aconitine activates the P38/MAPK/Nrf2 pathway, induces ROS increase, and promotes autophagy. NAC can inhibit proliferation inhibition, apoptosis, inflammation and P38/MAPK/Nrf2 pathway activation induced by aconitine. Rap and P38 activators can partially recover the effects of NAC on proliferation, apoptosis, inflammation and autophagy of cardiomyocytes. Conclusion Aconitine promotes ROS-activated P38/MAPK/Nrf2 pathway to inhibit autophagy and promote myocardial injury. |
| format | Article |
| id | doaj-art-ddc377090a0f4ee3adab53f9c8c7a4c9 |
| institution | Kabale University |
| issn | 1749-8090 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Cardiothoracic Surgery |
| spelling | doaj-art-ddc377090a0f4ee3adab53f9c8c7a4c92024-12-22T12:46:59ZengBMCJournal of Cardiothoracic Surgery1749-80902024-12-0119111410.1186/s13019-024-03149-0Aconitine promotes ROS-activated P38/MAPK/Nrf2 pathway to inhibit autophagy and promote myocardial injuryChunai Yang0Jinxiao Fu1Fenshuang Zheng2Yangshan Fu3Xueqiong Duan4Ruiling Zuo5Junbo Zhu6Department of Emergency, The Affiliated Hospital of Yunnan UniversityDepartment of Geriatric Medicine, The Affiliated Hospital of Yunnan UniversityDepartment of Emergency, The Affiliated Hospital of Yunnan UniversityDepartment of Emergency, The Affiliated Hospital of Yunnan UniversityDepartment of Emergency, The Affiliated Hospital of Yunnan UniversityDepartment of Emergency, The Affiliated Hospital of Yunnan UniversityDepartment of Emergency, The Affiliated Hospital of Yunnan UniversityAbstract Background Aconitine has cardiotoxicity, but the mechanism of cardiotoxicity induced by aconitine is limited. The aim of this study was to investigate the mechanism of myocardial injury induced by aconitine. Methods Using aconitine, ROS inhibitor N-acetylcysteine(NAC), the autophagy activitor Rapamycin (Rap) or the P38/MAPK pathway activitor Dehydrocorydaline treats H9C2 cells. CCK-8 assay was used to assay cell proliferation activity. Flow Cytometry was used to detect cell apoptosis. Dichloro-dihydrofluorescein diacetate was used to detect ROS levels. The expression of LC3 was detected by Immunofluorescence Staining. Western blotting detected the expression of related proteins. The mRNA levels of inflammatory factors were detected by RT-qPCR. Results Aconitine inhibits cardiomyocyte proliferation, induces apoptosis and secretion of inflammatory factors. Aconitine activates the P38/MAPK/Nrf2 pathway, induces ROS increase, and promotes autophagy. NAC can inhibit proliferation inhibition, apoptosis, inflammation and P38/MAPK/Nrf2 pathway activation induced by aconitine. Rap and P38 activators can partially recover the effects of NAC on proliferation, apoptosis, inflammation and autophagy of cardiomyocytes. Conclusion Aconitine promotes ROS-activated P38/MAPK/Nrf2 pathway to inhibit autophagy and promote myocardial injury.https://doi.org/10.1186/s13019-024-03149-0AconitineROSAutophagyP38/MAPK/Nrf2 pathwayMyocardial injury |
| spellingShingle | Chunai Yang Jinxiao Fu Fenshuang Zheng Yangshan Fu Xueqiong Duan Ruiling Zuo Junbo Zhu Aconitine promotes ROS-activated P38/MAPK/Nrf2 pathway to inhibit autophagy and promote myocardial injury Journal of Cardiothoracic Surgery Aconitine ROS Autophagy P38/MAPK/Nrf2 pathway Myocardial injury |
| title | Aconitine promotes ROS-activated P38/MAPK/Nrf2 pathway to inhibit autophagy and promote myocardial injury |
| title_full | Aconitine promotes ROS-activated P38/MAPK/Nrf2 pathway to inhibit autophagy and promote myocardial injury |
| title_fullStr | Aconitine promotes ROS-activated P38/MAPK/Nrf2 pathway to inhibit autophagy and promote myocardial injury |
| title_full_unstemmed | Aconitine promotes ROS-activated P38/MAPK/Nrf2 pathway to inhibit autophagy and promote myocardial injury |
| title_short | Aconitine promotes ROS-activated P38/MAPK/Nrf2 pathway to inhibit autophagy and promote myocardial injury |
| title_sort | aconitine promotes ros activated p38 mapk nrf2 pathway to inhibit autophagy and promote myocardial injury |
| topic | Aconitine ROS Autophagy P38/MAPK/Nrf2 pathway Myocardial injury |
| url | https://doi.org/10.1186/s13019-024-03149-0 |
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