Gastrodin reduces myocardial ischemia/reperfusion injury via transgelin2/CNPase-mediated apoptosis regulation
BackgroundMyocardial ischemia-reperfusion injury (MIRI) frequently occurs during rapid restoration of blood flow in the infarcted myocardium. While Gastrodin (GAS) mitigates MIRI, its mechanism requires further exploration.MethodsWe evaluated GAS effect in SD rats following 45-min left coronary arte...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1604408/full |
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| author | Changyan Li Peng Rao Xiang Liu Xiang Liu Lin Yang Lin Yang Yongliang Jiang Yongliang Jiang Gaosheng Yin Shuangxiu Li Shuangxiu Li Ping Yang Ping Yang Lin Sun |
| author_facet | Changyan Li Peng Rao Xiang Liu Xiang Liu Lin Yang Lin Yang Yongliang Jiang Yongliang Jiang Gaosheng Yin Shuangxiu Li Shuangxiu Li Ping Yang Ping Yang Lin Sun |
| author_sort | Changyan Li |
| collection | DOAJ |
| description | BackgroundMyocardial ischemia-reperfusion injury (MIRI) frequently occurs during rapid restoration of blood flow in the infarcted myocardium. While Gastrodin (GAS) mitigates MIRI, its mechanism requires further exploration.MethodsWe evaluated GAS effect in SD rats following 45-min left coronary artery ligation and reperfusion. GAS (intraperitoneal) was administered preoperatively for 3 days. Triphenyltetrazolium chloride (TTC) staining was used to detect infarct size. The cardiac function was monitored by the Langendorff isolated cardiac perfusion system. Hematoxylin-Eosin (H&E) staining was applied to detect cardiac injury. H9c2 cells underwent oxygen and glucose deprivation (OGD) and were subsequently restored to normal culture conditions, mimicking MIRI. Cell Counting Kit-8 (CCK-8) was used to detect the cytotoxicity of GAS. Myocardial cell injury was determined by detecting lactate dehydrogenase (LDH) level in the medium. The expression of protein was detected by Western blot (WB) and immunofluorescence (IF) assay. Coimmunocoprecipitation (Co-IP), coupled with molecular docking detected the combination among transgelin2 (TG2), and CNPase.ResultsGAS reduced the size of myocardial infarction, alleviated myocardial fiber damage, and ameliorated MIRI-mediated cardiac dysfunction. Mechanistically, GAS inhibited apoptosis by restoring MIRI-altered TG2/CNPase expression. TG2 directly bound and negatively regulated CNPase. CNPase deficiency enhanced MIRI amelioration by reducing apoptosis.ConclusionTaken together, GAS protects against MIRI by modulating apoptosis through the TG2/CNPase pathway, revealing a novel therapeutic target. |
| format | Article |
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| institution | DOAJ |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-72cf27dcfe3e4ab5a34ee1ee70326c052025-08-20T03:11:36ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-07-011610.3389/fphar.2025.16044081604408Gastrodin reduces myocardial ischemia/reperfusion injury via transgelin2/CNPase-mediated apoptosis regulationChangyan Li0Peng Rao1Xiang Liu2Xiang Liu3Lin Yang4Lin Yang5Yongliang Jiang6Yongliang Jiang7Gaosheng Yin8Shuangxiu Li9Shuangxiu Li10Ping Yang11Ping Yang12Lin Sun13Yunnan Key Laboratory of Stem Cell and Regenerative Medicine, School of Rehabilitation, Kunming Medical University, Kunming, ChinaYunnan Key Laboratory of Stem Cell and Regenerative Medicine, School of Rehabilitation, Kunming Medical University, Kunming, ChinaYunnan Key Laboratory of Stem Cell and Regenerative Medicine, School of Rehabilitation, Kunming Medical University, Kunming, ChinaDepartment of Orthopedic Surgery, The First People’s Hospital of Yunnan Province, Kunming, ChinaYunnan Key Laboratory of Stem Cell and Regenerative Medicine, School of Rehabilitation, Kunming Medical University, Kunming, ChinaDepartment of Cardiology, the Second Affiliated Hospital, Kunming Medical University, Kunming, ChinaYunnan Key Laboratory of Stem Cell and Regenerative Medicine, School of Rehabilitation, Kunming Medical University, Kunming, ChinaDepartment of Cardiology, the Second Affiliated Hospital, Kunming Medical University, Kunming, ChinaYunnan Key Laboratory of Stem Cell and Regenerative Medicine, School of Rehabilitation, Kunming Medical University, Kunming, ChinaYunnan Key Laboratory of Stem Cell and Regenerative Medicine, School of Rehabilitation, Kunming Medical University, Kunming, ChinaDepartment of Cardiology, the Second Affiliated Hospital, Kunming Medical University, Kunming, ChinaYunnan Key Laboratory of Stem Cell and Regenerative Medicine, School of Rehabilitation, Kunming Medical University, Kunming, ChinaDepartment of Cardiology, the Second Affiliated Hospital, Kunming Medical University, Kunming, ChinaDepartment of Cardiology, the Second Affiliated Hospital, Kunming Medical University, Kunming, ChinaBackgroundMyocardial ischemia-reperfusion injury (MIRI) frequently occurs during rapid restoration of blood flow in the infarcted myocardium. While Gastrodin (GAS) mitigates MIRI, its mechanism requires further exploration.MethodsWe evaluated GAS effect in SD rats following 45-min left coronary artery ligation and reperfusion. GAS (intraperitoneal) was administered preoperatively for 3 days. Triphenyltetrazolium chloride (TTC) staining was used to detect infarct size. The cardiac function was monitored by the Langendorff isolated cardiac perfusion system. Hematoxylin-Eosin (H&E) staining was applied to detect cardiac injury. H9c2 cells underwent oxygen and glucose deprivation (OGD) and were subsequently restored to normal culture conditions, mimicking MIRI. Cell Counting Kit-8 (CCK-8) was used to detect the cytotoxicity of GAS. Myocardial cell injury was determined by detecting lactate dehydrogenase (LDH) level in the medium. The expression of protein was detected by Western blot (WB) and immunofluorescence (IF) assay. Coimmunocoprecipitation (Co-IP), coupled with molecular docking detected the combination among transgelin2 (TG2), and CNPase.ResultsGAS reduced the size of myocardial infarction, alleviated myocardial fiber damage, and ameliorated MIRI-mediated cardiac dysfunction. Mechanistically, GAS inhibited apoptosis by restoring MIRI-altered TG2/CNPase expression. TG2 directly bound and negatively regulated CNPase. CNPase deficiency enhanced MIRI amelioration by reducing apoptosis.ConclusionTaken together, GAS protects against MIRI by modulating apoptosis through the TG2/CNPase pathway, revealing a novel therapeutic target.https://www.frontiersin.org/articles/10.3389/fphar.2025.1604408/fullmyocardial ischemia/reperfusion injuryGastrodinapoptosisCNPasetransgelin2 |
| spellingShingle | Changyan Li Peng Rao Xiang Liu Xiang Liu Lin Yang Lin Yang Yongliang Jiang Yongliang Jiang Gaosheng Yin Shuangxiu Li Shuangxiu Li Ping Yang Ping Yang Lin Sun Gastrodin reduces myocardial ischemia/reperfusion injury via transgelin2/CNPase-mediated apoptosis regulation Frontiers in Pharmacology myocardial ischemia/reperfusion injury Gastrodin apoptosis CNPase transgelin2 |
| title | Gastrodin reduces myocardial ischemia/reperfusion injury via transgelin2/CNPase-mediated apoptosis regulation |
| title_full | Gastrodin reduces myocardial ischemia/reperfusion injury via transgelin2/CNPase-mediated apoptosis regulation |
| title_fullStr | Gastrodin reduces myocardial ischemia/reperfusion injury via transgelin2/CNPase-mediated apoptosis regulation |
| title_full_unstemmed | Gastrodin reduces myocardial ischemia/reperfusion injury via transgelin2/CNPase-mediated apoptosis regulation |
| title_short | Gastrodin reduces myocardial ischemia/reperfusion injury via transgelin2/CNPase-mediated apoptosis regulation |
| title_sort | gastrodin reduces myocardial ischemia reperfusion injury via transgelin2 cnpase mediated apoptosis regulation |
| topic | myocardial ischemia/reperfusion injury Gastrodin apoptosis CNPase transgelin2 |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1604408/full |
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