Ginsenoside Rg5 alleviates hypoxia-induced myocardial apoptosis by targeting STAT3 to promote Tyr705 phosphorylation
Abstract Background The heart, as the body's blood-pumping organ, is extremely sensitive to changes in oxygen levels. Myocardial injury caused by hypoxia is a challenging issue, and there are currently no definitive specific drugs available for its treatment. Ginsenoside Rg5, one of the main ra...
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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/s13020-025-01128-8 |
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| author | Fang-yang Li Yi-hao Wang Cheng Zhang Wan-yun Dang Ze-kun Wu Zhen-hui Wu Jia-lu Cui Xiang-jun Wu Chun-qi Yang Xue-cong Tian Cheng-rong Xiao Yu-guang Wang Yue Gao |
| author_facet | Fang-yang Li Yi-hao Wang Cheng Zhang Wan-yun Dang Ze-kun Wu Zhen-hui Wu Jia-lu Cui Xiang-jun Wu Chun-qi Yang Xue-cong Tian Cheng-rong Xiao Yu-guang Wang Yue Gao |
| author_sort | Fang-yang Li |
| collection | DOAJ |
| description | Abstract Background The heart, as the body's blood-pumping organ, is extremely sensitive to changes in oxygen levels. Myocardial injury caused by hypoxia is a challenging issue, and there are currently no definitive specific drugs available for its treatment. Ginsenoside Rg5, one of the main rare saponins in ginseng, has shown significant efficacy in treating myocardial injury. This study aims to investigate the role and mechanisms of Rg5 in the treatment of hypoxic myocardial injury. Methods The cardioprotective effect against acute hypoxia of Rg5 was studied by assessing heart function, myocardial injury markers, inflammation, and oxidative stress in C57 mice, as well as apoptosis and reactive oxygen species (ROS) levels in H9c2 cardiomyocytes. Thermal proteome and target validation techniques were used to confirm the target protein of Rg5. The further protective mechanisms against hypoxia-induced damage were explored using immunocoprecipitation, immunofluorescence and rescue experiments in vivo and in vitro. Results The experimental results demonstrated that Rg5 effectively improved cardiac function in mice, reduced inflammation, oxidative stress, and the release of myocardial injury markers, decreased cardiomyocyte apoptosis, and lowered ROS levels. Further, using target protein screening and validation techniques, Signal transducer and activator of transcription 3 (STAT3) was verified as a direct target for Rg5's cardioprotective effect. It was observed that Rg5 specifically promoted the phosphorylation of Tyr705 in STAT3 via the JAK2/STAT3 pathway, leading to the translocation of phosphorylated STAT3 into the nucleus where they induce the expression of anti-apoptotic protein and protect cells from hypoxic damage. Conclusion Rg5 could be a potential therapeutic agent for preventing and treating myocardial hypoxic injury, providing scientific evidence for its application in anti-hypoxic therapy. |
| format | Article |
| id | doaj-art-d95ce1745b304d4dbe611c4b96544ccc |
| institution | OA Journals |
| issn | 1749-8546 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Chinese Medicine |
| spelling | doaj-art-d95ce1745b304d4dbe611c4b96544ccc2025-08-20T02:06:36ZengBMCChinese Medicine1749-85462025-06-0120112210.1186/s13020-025-01128-8Ginsenoside Rg5 alleviates hypoxia-induced myocardial apoptosis by targeting STAT3 to promote Tyr705 phosphorylationFang-yang Li0Yi-hao Wang1Cheng Zhang2Wan-yun Dang3Ze-kun Wu4Zhen-hui Wu5Jia-lu Cui6Xiang-jun Wu7Chun-qi Yang8Xue-cong Tian9Cheng-rong Xiao10Yu-guang Wang11Yue Gao12School of Pharmacy, Guangdong Pharmaceutical UniversityBeijing Institute of Radiation MedicineSchool of Pharmacy, Guangdong Pharmaceutical UniversitySchool of Pharmacy, Guangdong Pharmaceutical UniversitySchool of Pharmacy, Guangdong Pharmaceutical UniversityBeijing Institute of Radiation MedicineBeijing Institute of Radiation MedicineBeijing Institute of Radiation MedicineBeijing Institute of Radiation MedicineBeijing Institute of Radiation MedicineBeijing Institute of Radiation MedicineBeijing Institute of Radiation MedicineSchool of Pharmacy, Guangdong Pharmaceutical UniversityAbstract Background The heart, as the body's blood-pumping organ, is extremely sensitive to changes in oxygen levels. Myocardial injury caused by hypoxia is a challenging issue, and there are currently no definitive specific drugs available for its treatment. Ginsenoside Rg5, one of the main rare saponins in ginseng, has shown significant efficacy in treating myocardial injury. This study aims to investigate the role and mechanisms of Rg5 in the treatment of hypoxic myocardial injury. Methods The cardioprotective effect against acute hypoxia of Rg5 was studied by assessing heart function, myocardial injury markers, inflammation, and oxidative stress in C57 mice, as well as apoptosis and reactive oxygen species (ROS) levels in H9c2 cardiomyocytes. Thermal proteome and target validation techniques were used to confirm the target protein of Rg5. The further protective mechanisms against hypoxia-induced damage were explored using immunocoprecipitation, immunofluorescence and rescue experiments in vivo and in vitro. Results The experimental results demonstrated that Rg5 effectively improved cardiac function in mice, reduced inflammation, oxidative stress, and the release of myocardial injury markers, decreased cardiomyocyte apoptosis, and lowered ROS levels. Further, using target protein screening and validation techniques, Signal transducer and activator of transcription 3 (STAT3) was verified as a direct target for Rg5's cardioprotective effect. It was observed that Rg5 specifically promoted the phosphorylation of Tyr705 in STAT3 via the JAK2/STAT3 pathway, leading to the translocation of phosphorylated STAT3 into the nucleus where they induce the expression of anti-apoptotic protein and protect cells from hypoxic damage. Conclusion Rg5 could be a potential therapeutic agent for preventing and treating myocardial hypoxic injury, providing scientific evidence for its application in anti-hypoxic therapy.https://doi.org/10.1186/s13020-025-01128-8Ginsenoside Rg5Stat3Tyr705 phosphorylationHypoxiaMyocardial apoptosis |
| spellingShingle | Fang-yang Li Yi-hao Wang Cheng Zhang Wan-yun Dang Ze-kun Wu Zhen-hui Wu Jia-lu Cui Xiang-jun Wu Chun-qi Yang Xue-cong Tian Cheng-rong Xiao Yu-guang Wang Yue Gao Ginsenoside Rg5 alleviates hypoxia-induced myocardial apoptosis by targeting STAT3 to promote Tyr705 phosphorylation Chinese Medicine Ginsenoside Rg5 Stat3 Tyr705 phosphorylation Hypoxia Myocardial apoptosis |
| title | Ginsenoside Rg5 alleviates hypoxia-induced myocardial apoptosis by targeting STAT3 to promote Tyr705 phosphorylation |
| title_full | Ginsenoside Rg5 alleviates hypoxia-induced myocardial apoptosis by targeting STAT3 to promote Tyr705 phosphorylation |
| title_fullStr | Ginsenoside Rg5 alleviates hypoxia-induced myocardial apoptosis by targeting STAT3 to promote Tyr705 phosphorylation |
| title_full_unstemmed | Ginsenoside Rg5 alleviates hypoxia-induced myocardial apoptosis by targeting STAT3 to promote Tyr705 phosphorylation |
| title_short | Ginsenoside Rg5 alleviates hypoxia-induced myocardial apoptosis by targeting STAT3 to promote Tyr705 phosphorylation |
| title_sort | ginsenoside rg5 alleviates hypoxia induced myocardial apoptosis by targeting stat3 to promote tyr705 phosphorylation |
| topic | Ginsenoside Rg5 Stat3 Tyr705 phosphorylation Hypoxia Myocardial apoptosis |
| url | https://doi.org/10.1186/s13020-025-01128-8 |
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