Puerarin pretreatment provides protection against myocardial ischemia/reperfusion injury via inhibiting excessive autophagy and apoptosis by modulation of HES1
Abstract The study aimed to elucidate the underlying pharmacological mechanism of the traditional Chinese medicine Pue in ameliorating myocardial ischemia-reperfusion injury (MIRI), a critical clinical challenge exacerbated by reperfusion therapy. In vivo MIRI and in vitro anoxia/reoxygenation (A/R)...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-024-84808-z |
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| author | Yong Yuan Songqing Lai Tie Hu Fajia Hu Chenchao Zou Xiuqi Wang Ming Fang Jichun Liu Huang Huang |
| author_facet | Yong Yuan Songqing Lai Tie Hu Fajia Hu Chenchao Zou Xiuqi Wang Ming Fang Jichun Liu Huang Huang |
| author_sort | Yong Yuan |
| collection | DOAJ |
| description | Abstract The study aimed to elucidate the underlying pharmacological mechanism of the traditional Chinese medicine Pue in ameliorating myocardial ischemia-reperfusion injury (MIRI), a critical clinical challenge exacerbated by reperfusion therapy. In vivo MIRI and in vitro anoxia/reoxygenation (A/R) models were constructed. The results demonstrated that Pue pretreatment effectively alleviated MIRI, as manifested by diminishing the levels of serum CK-MB and LDH, mitigating the extent of myocardial infarction and enhancing cardiac functionality. Additionally, Pue significantly alleviated histopathological damage in MIRI-treated myocardium, as evidenced by HE staining and TUNEL assay. In vitro, Pue pretreatment significantly alleviated A/R-induced damage by decreasing LDH levels, increasing cellular activity, inhibiting autophagic lysosomal overactivation, inhibiting oxidative stress (ROS, LIP ROS, MDA), increasing antioxidant defense (SOD, GSH-Px), and increasing P62 protein expression while decreasing LC3II/I ratio. Furthermore, Pue inhibited apoptosis and maintained mitochondrial homeostasis by up-regulating the expression of Hairy and Enhancer of Split-1 (HES1) protein, which was crucial for its cardioprotective effects. Nevertheless, the cardioprotective efficacy of Pue pretreatment was negated via the knockdown of HES1 protein expression via pAD/HES1-shRNA transfection. In conclusion, Pue effectively ameliorated HES1-mediated MIRI-induced autophagy, apoptosis, and mitochondrial dysfunction. |
| format | Article |
| id | doaj-art-3234d6ca6399468e9bb77d2829c9a4ab |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-3234d6ca6399468e9bb77d2829c9a4ab2025-01-05T12:14:17ZengNature PortfolioScientific Reports2045-23222025-01-0115111510.1038/s41598-024-84808-zPuerarin pretreatment provides protection against myocardial ischemia/reperfusion injury via inhibiting excessive autophagy and apoptosis by modulation of HES1Yong Yuan0Songqing Lai1Tie Hu2Fajia Hu3Chenchao Zou4Xiuqi Wang5Ming Fang6Jichun Liu7Huang Huang8Department of Cardiovascular Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Cardiovascular Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Cardiovascular Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Cardiovascular Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Cardiovascular Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Cardiovascular Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Emergency, Gaoxin Branch of The First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Cardiovascular Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Cardiovascular Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityAbstract The study aimed to elucidate the underlying pharmacological mechanism of the traditional Chinese medicine Pue in ameliorating myocardial ischemia-reperfusion injury (MIRI), a critical clinical challenge exacerbated by reperfusion therapy. In vivo MIRI and in vitro anoxia/reoxygenation (A/R) models were constructed. The results demonstrated that Pue pretreatment effectively alleviated MIRI, as manifested by diminishing the levels of serum CK-MB and LDH, mitigating the extent of myocardial infarction and enhancing cardiac functionality. Additionally, Pue significantly alleviated histopathological damage in MIRI-treated myocardium, as evidenced by HE staining and TUNEL assay. In vitro, Pue pretreatment significantly alleviated A/R-induced damage by decreasing LDH levels, increasing cellular activity, inhibiting autophagic lysosomal overactivation, inhibiting oxidative stress (ROS, LIP ROS, MDA), increasing antioxidant defense (SOD, GSH-Px), and increasing P62 protein expression while decreasing LC3II/I ratio. Furthermore, Pue inhibited apoptosis and maintained mitochondrial homeostasis by up-regulating the expression of Hairy and Enhancer of Split-1 (HES1) protein, which was crucial for its cardioprotective effects. Nevertheless, the cardioprotective efficacy of Pue pretreatment was negated via the knockdown of HES1 protein expression via pAD/HES1-shRNA transfection. In conclusion, Pue effectively ameliorated HES1-mediated MIRI-induced autophagy, apoptosis, and mitochondrial dysfunction.https://doi.org/10.1038/s41598-024-84808-zMyocardial ischemia/reperfusion injuryPuerarinHES1AutophagyApoptosis |
| spellingShingle | Yong Yuan Songqing Lai Tie Hu Fajia Hu Chenchao Zou Xiuqi Wang Ming Fang Jichun Liu Huang Huang Puerarin pretreatment provides protection against myocardial ischemia/reperfusion injury via inhibiting excessive autophagy and apoptosis by modulation of HES1 Scientific Reports Myocardial ischemia/reperfusion injury Puerarin HES1 Autophagy Apoptosis |
| title | Puerarin pretreatment provides protection against myocardial ischemia/reperfusion injury via inhibiting excessive autophagy and apoptosis by modulation of HES1 |
| title_full | Puerarin pretreatment provides protection against myocardial ischemia/reperfusion injury via inhibiting excessive autophagy and apoptosis by modulation of HES1 |
| title_fullStr | Puerarin pretreatment provides protection against myocardial ischemia/reperfusion injury via inhibiting excessive autophagy and apoptosis by modulation of HES1 |
| title_full_unstemmed | Puerarin pretreatment provides protection against myocardial ischemia/reperfusion injury via inhibiting excessive autophagy and apoptosis by modulation of HES1 |
| title_short | Puerarin pretreatment provides protection against myocardial ischemia/reperfusion injury via inhibiting excessive autophagy and apoptosis by modulation of HES1 |
| title_sort | puerarin pretreatment provides protection against myocardial ischemia reperfusion injury via inhibiting excessive autophagy and apoptosis by modulation of hes1 |
| topic | Myocardial ischemia/reperfusion injury Puerarin HES1 Autophagy Apoptosis |
| url | https://doi.org/10.1038/s41598-024-84808-z |
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