Natural product library screening identifies Darutigenol for the treatment of myocardial infarction and ischemia/reperfusion injury
Abstract Introduction Ischemic heart diseases are the leading cause of death worldwide due to the inability of regeneration of adult cardiomyocytes (CMs). Natural products from medical herbs are an important source of innovative drugs for many diseases including cardiovascular diseases. Objectives I...
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BMC
2025-06-01
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| Series: | Chinese Medicine |
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| Online Access: | https://doi.org/10.1186/s13020-025-01141-x |
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| author | Kun Liu Li Zheng Qian-Yu Huang Hong-Ji Li Cheng Li Hui Zhao Ze-Bing Ye Hao Wang Xu-Feng Qi Meng Wang |
| author_facet | Kun Liu Li Zheng Qian-Yu Huang Hong-Ji Li Cheng Li Hui Zhao Ze-Bing Ye Hao Wang Xu-Feng Qi Meng Wang |
| author_sort | Kun Liu |
| collection | DOAJ |
| description | Abstract Introduction Ischemic heart diseases are the leading cause of death worldwide due to the inability of regeneration of adult cardiomyocytes (CMs). Natural products from medical herbs are an important source of innovative drugs for many diseases including cardiovascular diseases. Objectives In this study, we set out to screen novel small-molecule therapies from natural products to protect heart against ischemic injury. Methods High-throughput screening was performed using a natural product library to identify the potential small molecules which can promote survival of CMs under ischemic and ischemic/reperfusion conditions. In addition, myocardial infarction (MI) and ischemia/reperfusion (I/R) mice models were used to evaluate the in vivo effects of the screened candidate. We also applied various analysis including cell viability, qPCR, Western blot, immunofluorescent staining, echocardiography, Masson’s staining, TTC staining, and network pharmacology. Results High-throughput screening showed that the small molecule compound Darutigenol (Dar), derived from the Chinese traditional herb Herba Siegesbeckiae, could significantly promote CM survival and proliferation under ischemic conditions. Moreover, I/R-induced CM apoptosis and ROS generation could be significantly reduced by Dar treatment. In addition, in vivo administration of Dar was able to attenuate MI- and I/R-induced cardiac injury in adult mice by decreasing fibrosis and apoptosis, thereby improving cardiac function. Network pharmacology analysis and molecule docking assay showed that Dar has the highest binding affinity with AKT1 protein. Western blotting assay further revealed that AKT1 activation was significantly enhanced by Dar administration in the infarcted hearts. Conclusions Our data revealed that the small molecule compound Dar, screened from the natural product library in this study, is capable of protecting heart against MI and I/R injury by activating AKT1 pathway. These findings enrich the natural product candidates for cardiovascular disease treatment and provide new insights into potential therapeutic agents for MI and I/R injury. |
| format | Article |
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| institution | Kabale University |
| issn | 1749-8546 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Chinese Medicine |
| spelling | doaj-art-35edfd677f964b0fa5d5f95e8689d5442025-08-20T03:47:16ZengBMCChinese Medicine1749-85462025-06-0120111510.1186/s13020-025-01141-xNatural product library screening identifies Darutigenol for the treatment of myocardial infarction and ischemia/reperfusion injuryKun Liu0Li Zheng1Qian-Yu Huang2Hong-Ji Li3Cheng Li4Hui Zhao5Ze-Bing Ye6Hao Wang7Xu-Feng Qi8Meng Wang9Department of Cardiology, Zhongshan Torch Development Zone People’s HospitalSchool of Environmental Science and Engineering, Guangdong University of TechnologyKey Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Department of Developmental & Regenerative Biology, and Department of Cardiology, The Affiliated Guangdong Second Provincial General Hospital, Jinan UniversityKey Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Department of Developmental & Regenerative Biology, and Department of Cardiology, The Affiliated Guangdong Second Provincial General Hospital, Jinan UniversityKey Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Department of Developmental & Regenerative Biology, and Department of Cardiology, The Affiliated Guangdong Second Provincial General Hospital, Jinan UniversityKey Laboratory of Regenerative Medicine of Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong KongDepartment of Cardiology, The Affiliated Guangdong Second Provincial General Hospital, Jinan UniversityDepartment of Anesthesiology & Clinical Research Center, The First Affiliated Hospital, Jinan UniversityKey Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Department of Developmental & Regenerative Biology, and Department of Cardiology, The Affiliated Guangdong Second Provincial General Hospital, Jinan UniversityDepartment of Cardiology, Zhongshan Torch Development Zone People’s HospitalAbstract Introduction Ischemic heart diseases are the leading cause of death worldwide due to the inability of regeneration of adult cardiomyocytes (CMs). Natural products from medical herbs are an important source of innovative drugs for many diseases including cardiovascular diseases. Objectives In this study, we set out to screen novel small-molecule therapies from natural products to protect heart against ischemic injury. Methods High-throughput screening was performed using a natural product library to identify the potential small molecules which can promote survival of CMs under ischemic and ischemic/reperfusion conditions. In addition, myocardial infarction (MI) and ischemia/reperfusion (I/R) mice models were used to evaluate the in vivo effects of the screened candidate. We also applied various analysis including cell viability, qPCR, Western blot, immunofluorescent staining, echocardiography, Masson’s staining, TTC staining, and network pharmacology. Results High-throughput screening showed that the small molecule compound Darutigenol (Dar), derived from the Chinese traditional herb Herba Siegesbeckiae, could significantly promote CM survival and proliferation under ischemic conditions. Moreover, I/R-induced CM apoptosis and ROS generation could be significantly reduced by Dar treatment. In addition, in vivo administration of Dar was able to attenuate MI- and I/R-induced cardiac injury in adult mice by decreasing fibrosis and apoptosis, thereby improving cardiac function. Network pharmacology analysis and molecule docking assay showed that Dar has the highest binding affinity with AKT1 protein. Western blotting assay further revealed that AKT1 activation was significantly enhanced by Dar administration in the infarcted hearts. Conclusions Our data revealed that the small molecule compound Dar, screened from the natural product library in this study, is capable of protecting heart against MI and I/R injury by activating AKT1 pathway. These findings enrich the natural product candidates for cardiovascular disease treatment and provide new insights into potential therapeutic agents for MI and I/R injury.https://doi.org/10.1186/s13020-025-01141-xDrug screeningDarutigenolMyocardial infarctionIschemic/reperfusion injury |
| spellingShingle | Kun Liu Li Zheng Qian-Yu Huang Hong-Ji Li Cheng Li Hui Zhao Ze-Bing Ye Hao Wang Xu-Feng Qi Meng Wang Natural product library screening identifies Darutigenol for the treatment of myocardial infarction and ischemia/reperfusion injury Chinese Medicine Drug screening Darutigenol Myocardial infarction Ischemic/reperfusion injury |
| title | Natural product library screening identifies Darutigenol for the treatment of myocardial infarction and ischemia/reperfusion injury |
| title_full | Natural product library screening identifies Darutigenol for the treatment of myocardial infarction and ischemia/reperfusion injury |
| title_fullStr | Natural product library screening identifies Darutigenol for the treatment of myocardial infarction and ischemia/reperfusion injury |
| title_full_unstemmed | Natural product library screening identifies Darutigenol for the treatment of myocardial infarction and ischemia/reperfusion injury |
| title_short | Natural product library screening identifies Darutigenol for the treatment of myocardial infarction and ischemia/reperfusion injury |
| title_sort | natural product library screening identifies darutigenol for the treatment of myocardial infarction and ischemia reperfusion injury |
| topic | Drug screening Darutigenol Myocardial infarction Ischemic/reperfusion injury |
| url | https://doi.org/10.1186/s13020-025-01141-x |
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