Ginsenoside Rb1 ameliorates post-doxorubicin treatment myocardial hypertrophy via CaN/NFATc4/GATA4
Background: Myocardial hypertrophy is a crucial pathological change that occurs during post-anthracycline treatment cardiomyopathy. The effects of ginsenoside Rb1 (Rb1) on anthracycline-induced hypertrophy remain unclear. This study aimed to explore the antihypertrophic effect of Rb1 on post-doxorub...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-09-01
|
| Series: | Journal of Ginseng Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1226845325000958 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849243012117299200 |
|---|---|
| author | Jin-Jin Chang Li-Xia Xu Wen-Jing Yi Huan-Huan Zhang Jun-Wei Zhang Bin Zheng Ping-Ying Fu Rui-Lan He Rui-Xing Wang Jian-Feng Jiang Long-Xin Gui Min-Xia Wu Jun-Jin Lin Zhi-Hong Huang Jia-Lin Song Mo-Jun Lin Hai-Xia Jiao Zhi-Juan Wu |
| author_facet | Jin-Jin Chang Li-Xia Xu Wen-Jing Yi Huan-Huan Zhang Jun-Wei Zhang Bin Zheng Ping-Ying Fu Rui-Lan He Rui-Xing Wang Jian-Feng Jiang Long-Xin Gui Min-Xia Wu Jun-Jin Lin Zhi-Hong Huang Jia-Lin Song Mo-Jun Lin Hai-Xia Jiao Zhi-Juan Wu |
| author_sort | Jin-Jin Chang |
| collection | DOAJ |
| description | Background: Myocardial hypertrophy is a crucial pathological change that occurs during post-anthracycline treatment cardiomyopathy. The effects of ginsenoside Rb1 (Rb1) on anthracycline-induced hypertrophy remain unclear. This study aimed to explore the antihypertrophic effect of Rb1 on post-doxorubicin (DOX) treatment myocardial hypertrophy and underlying mechanism. Methods: Post-DOX treatment myocardial hypertrophy was induced 12 days or 22 h after 15 mg/kg DOX injection in C57BL/6 mice or 2 h DOX (2 μM) incubation in H9c2 cardiomyoblasts. Rb1 was administered 2 days before DOX exposure for 14 consecutive days or 6 h before DOX incubation for 30 h. Heart weight/Body weight (HW/BW), heart weight/tibia length (HW/TL) ratios, echocardiography, WGA staining and the contents of α-SMA, BNP and β-MCH were used to validate myocardial hypertrophy. HE staining, Masson staining, and transmission electron microscopy were performed to assess changes in cardiac morphology. Fluo-3/AM fluorescence was applied to measure the cytosolic free calcium concentration. Western blot, immunohistochemical and immunofluorescence staining were used to assess the expression of CaNBβ/NFATc4/GATA4 signaling. Results: Rb1 significantly decreased the HW/BW, HW/TL and LVd mass/BW ratios, reduced the cardiomyocyte area and the expression of BNP, β-MHC and α-SMA. Rb1 also relieved myocardial fibrosis and subcellar structure changes and improved the cardiac hemodynamics of post-DOX treatment mice. Rb1 decreased post-DOX treatment calcium overload. Consistent with these findings, in vivo and in vitro CaN, NFATc4 and GATA4 overexpression was rectified. Conclusion: Rb1 ameliorated post-doxorubicin treatment myocardial hypertrophy, which may be correlated with CaN/NFAT/GATA4 downregulation. |
| format | Article |
| id | doaj-art-5577bade34624d268ee4bc0f0b1373a5 |
| institution | Kabale University |
| issn | 1226-8453 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Ginseng Research |
| spelling | doaj-art-5577bade34624d268ee4bc0f0b1373a52025-08-20T03:59:37ZengElsevierJournal of Ginseng Research1226-84532025-09-0149558559310.1016/j.jgr.2025.06.003Ginsenoside Rb1 ameliorates post-doxorubicin treatment myocardial hypertrophy via CaN/NFATc4/GATA4Jin-Jin Chang0Li-Xia Xu1Wen-Jing Yi2Huan-Huan Zhang3Jun-Wei Zhang4Bin Zheng5Ping-Ying Fu6Rui-Lan He7Rui-Xing Wang8Jian-Feng Jiang9Long-Xin Gui10Min-Xia Wu11Jun-Jin Lin12Zhi-Hong Huang13Jia-Lin Song14Mo-Jun Lin15Hai-Xia Jiao16Zhi-Juan Wu17The Key Laboratory of Fujian Province Universities on Ion Channel and Signal Transduction in Cardiovascular Diseases, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China; Department of Physiology and Pathophysiology, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China; Department of Pathology, Air Force Medical Center, Beijing, ChinaThe Key Laboratory of Fujian Province Universities on Ion Channel and Signal Transduction in Cardiovascular Diseases, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China; Department of Physiology and Pathophysiology, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China; Department of Pathology, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, Zhejiang, ChinaThe Key Laboratory of Fujian Province Universities on Ion Channel and Signal Transduction in Cardiovascular Diseases, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China; Department of Physiology and Pathophysiology, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, ChinaThe Key Laboratory of Fujian Province Universities on Ion Channel and Signal Transduction in Cardiovascular Diseases, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China; Department of Physiology and Pathophysiology, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, ChinaThe Key Laboratory of Fujian Province Universities on Ion Channel and Signal Transduction in Cardiovascular Diseases, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China; Department of Physiology and Pathophysiology, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, ChinaDepartment of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, China; The School of Pharmacy, Fujian Medical University, Fuzhou, Fujian, ChinaThe Key Laboratory of Fujian Province Universities on Ion Channel and Signal Transduction in Cardiovascular Diseases, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China; Department of Physiology and Pathophysiology, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, ChinaThe Key Laboratory of Fujian Province Universities on Ion Channel and Signal Transduction in Cardiovascular Diseases, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China; Department of Physiology and Pathophysiology, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, ChinaThe Key Laboratory of Fujian Province Universities on Ion Channel and Signal Transduction in Cardiovascular Diseases, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China; Department of Physiology and Pathophysiology, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, ChinaThe Key Laboratory of Fujian Province Universities on Ion Channel and Signal Transduction in Cardiovascular Diseases, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China; Department of Physiology and Pathophysiology, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, ChinaThe Key Laboratory of Fujian Province Universities on Ion Channel and Signal Transduction in Cardiovascular Diseases, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, ChinaPublic Technology Service Center, Fujian Medical University, Fuzhou, Fujian, ChinaPublic Technology Service Center, Fujian Medical University, Fuzhou, Fujian, ChinaPublic Technology Service Center, Fujian Medical University, Fuzhou, Fujian, ChinaFujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, China; Corresponding authors. Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, 19 Jinjishan Road, Jinan County, Fuzhou, Fujian Province, 350011, People's Republic of China.The Key Laboratory of Fujian Province Universities on Ion Channel and Signal Transduction in Cardiovascular Diseases, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China; Department of Physiology and Pathophysiology, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China; Corresponding author. Department of Physiology and Pathophysiology, Fujian Medical University, 1 Xueyuan Road, Shangjie Zhen, Minhou County, Fuzhou, Fujian Province, 350122, People's Republic of China.The Key Laboratory of Fujian Province Universities on Ion Channel and Signal Transduction in Cardiovascular Diseases, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China; Department of Physiology and Pathophysiology, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China; Corresponding authors. Department of Physiology and Pathophysiology, Fujian Medical University, 1 Xueyuan Road, Shangjie Zhen, Minhou County, Fuzhou, Fujian Province, 350122, People's Republic of China.The Key Laboratory of Fujian Province Universities on Ion Channel and Signal Transduction in Cardiovascular Diseases, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China; Department of Physiology and Pathophysiology, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China; Corresponding author. Department of Physiology and Pathophysiology, Fujian Medical University, 1 Xueyuan Road, Shangjie Zhen, Minhou County, Fuzhou, Fujian Province, 350122, People's Republic of China.Background: Myocardial hypertrophy is a crucial pathological change that occurs during post-anthracycline treatment cardiomyopathy. The effects of ginsenoside Rb1 (Rb1) on anthracycline-induced hypertrophy remain unclear. This study aimed to explore the antihypertrophic effect of Rb1 on post-doxorubicin (DOX) treatment myocardial hypertrophy and underlying mechanism. Methods: Post-DOX treatment myocardial hypertrophy was induced 12 days or 22 h after 15 mg/kg DOX injection in C57BL/6 mice or 2 h DOX (2 μM) incubation in H9c2 cardiomyoblasts. Rb1 was administered 2 days before DOX exposure for 14 consecutive days or 6 h before DOX incubation for 30 h. Heart weight/Body weight (HW/BW), heart weight/tibia length (HW/TL) ratios, echocardiography, WGA staining and the contents of α-SMA, BNP and β-MCH were used to validate myocardial hypertrophy. HE staining, Masson staining, and transmission electron microscopy were performed to assess changes in cardiac morphology. Fluo-3/AM fluorescence was applied to measure the cytosolic free calcium concentration. Western blot, immunohistochemical and immunofluorescence staining were used to assess the expression of CaNBβ/NFATc4/GATA4 signaling. Results: Rb1 significantly decreased the HW/BW, HW/TL and LVd mass/BW ratios, reduced the cardiomyocyte area and the expression of BNP, β-MHC and α-SMA. Rb1 also relieved myocardial fibrosis and subcellar structure changes and improved the cardiac hemodynamics of post-DOX treatment mice. Rb1 decreased post-DOX treatment calcium overload. Consistent with these findings, in vivo and in vitro CaN, NFATc4 and GATA4 overexpression was rectified. Conclusion: Rb1 ameliorated post-doxorubicin treatment myocardial hypertrophy, which may be correlated with CaN/NFAT/GATA4 downregulation.http://www.sciencedirect.com/science/article/pii/S1226845325000958Ginsenoside Rb1Post-doxorubicin treatmentMyocardial hypertrophyFibrosisCaN/NFATc4/GATA4 |
| spellingShingle | Jin-Jin Chang Li-Xia Xu Wen-Jing Yi Huan-Huan Zhang Jun-Wei Zhang Bin Zheng Ping-Ying Fu Rui-Lan He Rui-Xing Wang Jian-Feng Jiang Long-Xin Gui Min-Xia Wu Jun-Jin Lin Zhi-Hong Huang Jia-Lin Song Mo-Jun Lin Hai-Xia Jiao Zhi-Juan Wu Ginsenoside Rb1 ameliorates post-doxorubicin treatment myocardial hypertrophy via CaN/NFATc4/GATA4 Journal of Ginseng Research Ginsenoside Rb1 Post-doxorubicin treatment Myocardial hypertrophy Fibrosis CaN/NFATc4/GATA4 |
| title | Ginsenoside Rb1 ameliorates post-doxorubicin treatment myocardial hypertrophy via CaN/NFATc4/GATA4 |
| title_full | Ginsenoside Rb1 ameliorates post-doxorubicin treatment myocardial hypertrophy via CaN/NFATc4/GATA4 |
| title_fullStr | Ginsenoside Rb1 ameliorates post-doxorubicin treatment myocardial hypertrophy via CaN/NFATc4/GATA4 |
| title_full_unstemmed | Ginsenoside Rb1 ameliorates post-doxorubicin treatment myocardial hypertrophy via CaN/NFATc4/GATA4 |
| title_short | Ginsenoside Rb1 ameliorates post-doxorubicin treatment myocardial hypertrophy via CaN/NFATc4/GATA4 |
| title_sort | ginsenoside rb1 ameliorates post doxorubicin treatment myocardial hypertrophy via can nfatc4 gata4 |
| topic | Ginsenoside Rb1 Post-doxorubicin treatment Myocardial hypertrophy Fibrosis CaN/NFATc4/GATA4 |
| url | http://www.sciencedirect.com/science/article/pii/S1226845325000958 |
| work_keys_str_mv | AT jinjinchang ginsenosiderb1amelioratespostdoxorubicintreatmentmyocardialhypertrophyviacannfatc4gata4 AT lixiaxu ginsenosiderb1amelioratespostdoxorubicintreatmentmyocardialhypertrophyviacannfatc4gata4 AT wenjingyi ginsenosiderb1amelioratespostdoxorubicintreatmentmyocardialhypertrophyviacannfatc4gata4 AT huanhuanzhang ginsenosiderb1amelioratespostdoxorubicintreatmentmyocardialhypertrophyviacannfatc4gata4 AT junweizhang ginsenosiderb1amelioratespostdoxorubicintreatmentmyocardialhypertrophyviacannfatc4gata4 AT binzheng ginsenosiderb1amelioratespostdoxorubicintreatmentmyocardialhypertrophyviacannfatc4gata4 AT pingyingfu ginsenosiderb1amelioratespostdoxorubicintreatmentmyocardialhypertrophyviacannfatc4gata4 AT ruilanhe ginsenosiderb1amelioratespostdoxorubicintreatmentmyocardialhypertrophyviacannfatc4gata4 AT ruixingwang ginsenosiderb1amelioratespostdoxorubicintreatmentmyocardialhypertrophyviacannfatc4gata4 AT jianfengjiang ginsenosiderb1amelioratespostdoxorubicintreatmentmyocardialhypertrophyviacannfatc4gata4 AT longxingui ginsenosiderb1amelioratespostdoxorubicintreatmentmyocardialhypertrophyviacannfatc4gata4 AT minxiawu ginsenosiderb1amelioratespostdoxorubicintreatmentmyocardialhypertrophyviacannfatc4gata4 AT junjinlin ginsenosiderb1amelioratespostdoxorubicintreatmentmyocardialhypertrophyviacannfatc4gata4 AT zhihonghuang ginsenosiderb1amelioratespostdoxorubicintreatmentmyocardialhypertrophyviacannfatc4gata4 AT jialinsong ginsenosiderb1amelioratespostdoxorubicintreatmentmyocardialhypertrophyviacannfatc4gata4 AT mojunlin ginsenosiderb1amelioratespostdoxorubicintreatmentmyocardialhypertrophyviacannfatc4gata4 AT haixiajiao ginsenosiderb1amelioratespostdoxorubicintreatmentmyocardialhypertrophyviacannfatc4gata4 AT zhijuanwu ginsenosiderb1amelioratespostdoxorubicintreatmentmyocardialhypertrophyviacannfatc4gata4 |