Ginsenoside Rb<sub>1</sub> Ameliorates Heart Failure Ventricular Remodeling by Regulating the Twist1/PGC-1α/PPARα Signaling Pathway
<b>Background:</b> Heart failure (HF), the terminal stage of cardiovascular disease with high morbidity and mortality, remains poorly managed by current therapies. Ventricular remodeling in HF is fundamentally characterized by myocardial fibrosis. While ginsenoside Rb<sub>1</sub...
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2025-03-01
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| author | Ziwei Zhou Zhimin Song Xiaomeng Guo Qi Wang Meijing Li Minyu Zhang Muxin Gong |
| author_facet | Ziwei Zhou Zhimin Song Xiaomeng Guo Qi Wang Meijing Li Minyu Zhang Muxin Gong |
| author_sort | Ziwei Zhou |
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| description | <b>Background:</b> Heart failure (HF), the terminal stage of cardiovascular disease with high morbidity and mortality, remains poorly managed by current therapies. Ventricular remodeling in HF is fundamentally characterized by myocardial fibrosis. While ginsenoside Rb<sub>1</sub> has demonstrated anti-fibrotic effects in HF, the underlying mechanism remains unclear. Twist1, an upstream regulator of energy metabolism factors PGC-1α and PPARα, may attenuate fibrosis by preserving systemic energy homeostasis, suggesting its pivotal role in HF pathogenesis. This study explores ginsenoside Rb<sub>1</sub>′s anti-HF mechanisms through the regulation of ginsenoside Rb<sub>1</sub> on these metabolic regulators. <b>Methods:</b> Sprague Dawley rats were subjected to a ligation of the left anterior descending coronary artery to induce an HF model, followed by ginsenoside Rb<sub>1</sub> treatment for 6 weeks. Therapeutic effects were evaluated through cardiac function assessment, myocardial histopathological staining (HE, Masson, immunofluorescence, immunohistochemistry), mitochondrial morphology observation (transmission electron microscopy), energy metabolism analysis (electron transport chain efficiency, mitochondrial membrane potential, ATP content), and protein expression profiling (Twist1, PGC-1α, PPARα, GLUT4, PPARγ). Additionally, H9c2 cells induced with endothelin-1 to model HF were employed as an in vitro model to further investigate ginsenoside Rb<sub>1</sub>′s regulatory effects on the Twist1/PGC-1α/PPARα signaling pathway. <b>Results:</b> Ginsenoside Rb<sub>1</sub> can restore cardiac function in HF rats, improve mitochondrial function, alleviate energy metabolism disorders, and inhibit ventricular remodeling. By modulating the Twist1/PGC-1α/PPARα signaling pathway, ginsenoside Rb<sub>1</sub> suppressed the abnormal overexpression of Twist1 and maintained normal expression of downstream PGC-1α and PPARα. In vitro experiments further demonstrated that ginsenoside Rb<sub>1</sub> significantly inhibited Twist1 expression in H9c2 cardiomyocytes with HF while promoting PGC-1α and PPARα expression, thereby restoring myocardial energy metabolism and mitigating ventricular remodeling in HF. <b>Conclusions:</b> Ginsenoside Rb<sub>1</sub> can inhibit the upregulation of Twist1 and activate the expression of its downstream PGC-1α and PPARα expression, by modulating the Twist1/PGC-1α/PPARα signaling pathway, alleviating ventricular remodeling in HF patients and improving myocardial energy metabolism dysfunction. Twist1 may be a key target for the treatment of HF. This study not only elucidates the mechanism by which ginsenoside Rb<sub>1</sub> alleviates HF, but also provides new insights into the clinical treatment of HF. |
| format | Article |
| id | doaj-art-8b37c72dcce042e99c00aaf0dc0ac117 |
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| spelling | doaj-art-8b37c72dcce042e99c00aaf0dc0ac1172025-08-20T02:18:20ZengMDPI AGPharmaceuticals1424-82472025-03-0118450010.3390/ph18040500Ginsenoside Rb<sub>1</sub> Ameliorates Heart Failure Ventricular Remodeling by Regulating the Twist1/PGC-1α/PPARα Signaling PathwayZiwei Zhou0Zhimin Song1Xiaomeng Guo2Qi Wang3Meijing Li4Minyu Zhang5Muxin Gong6School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, ChinaSchool of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, ChinaSchool of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, ChinaSchool of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, ChinaSchool of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, ChinaSchool of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, ChinaSchool of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China<b>Background:</b> Heart failure (HF), the terminal stage of cardiovascular disease with high morbidity and mortality, remains poorly managed by current therapies. Ventricular remodeling in HF is fundamentally characterized by myocardial fibrosis. While ginsenoside Rb<sub>1</sub> has demonstrated anti-fibrotic effects in HF, the underlying mechanism remains unclear. Twist1, an upstream regulator of energy metabolism factors PGC-1α and PPARα, may attenuate fibrosis by preserving systemic energy homeostasis, suggesting its pivotal role in HF pathogenesis. This study explores ginsenoside Rb<sub>1</sub>′s anti-HF mechanisms through the regulation of ginsenoside Rb<sub>1</sub> on these metabolic regulators. <b>Methods:</b> Sprague Dawley rats were subjected to a ligation of the left anterior descending coronary artery to induce an HF model, followed by ginsenoside Rb<sub>1</sub> treatment for 6 weeks. Therapeutic effects were evaluated through cardiac function assessment, myocardial histopathological staining (HE, Masson, immunofluorescence, immunohistochemistry), mitochondrial morphology observation (transmission electron microscopy), energy metabolism analysis (electron transport chain efficiency, mitochondrial membrane potential, ATP content), and protein expression profiling (Twist1, PGC-1α, PPARα, GLUT4, PPARγ). Additionally, H9c2 cells induced with endothelin-1 to model HF were employed as an in vitro model to further investigate ginsenoside Rb<sub>1</sub>′s regulatory effects on the Twist1/PGC-1α/PPARα signaling pathway. <b>Results:</b> Ginsenoside Rb<sub>1</sub> can restore cardiac function in HF rats, improve mitochondrial function, alleviate energy metabolism disorders, and inhibit ventricular remodeling. By modulating the Twist1/PGC-1α/PPARα signaling pathway, ginsenoside Rb<sub>1</sub> suppressed the abnormal overexpression of Twist1 and maintained normal expression of downstream PGC-1α and PPARα. In vitro experiments further demonstrated that ginsenoside Rb<sub>1</sub> significantly inhibited Twist1 expression in H9c2 cardiomyocytes with HF while promoting PGC-1α and PPARα expression, thereby restoring myocardial energy metabolism and mitigating ventricular remodeling in HF. <b>Conclusions:</b> Ginsenoside Rb<sub>1</sub> can inhibit the upregulation of Twist1 and activate the expression of its downstream PGC-1α and PPARα expression, by modulating the Twist1/PGC-1α/PPARα signaling pathway, alleviating ventricular remodeling in HF patients and improving myocardial energy metabolism dysfunction. Twist1 may be a key target for the treatment of HF. This study not only elucidates the mechanism by which ginsenoside Rb<sub>1</sub> alleviates HF, but also provides new insights into the clinical treatment of HF.https://www.mdpi.com/1424-8247/18/4/500heart failureTwist homolog 1 (Twist1)ginsenoside Rb<sub>1</sub>myocardial energy metabolism disorder |
| spellingShingle | Ziwei Zhou Zhimin Song Xiaomeng Guo Qi Wang Meijing Li Minyu Zhang Muxin Gong Ginsenoside Rb<sub>1</sub> Ameliorates Heart Failure Ventricular Remodeling by Regulating the Twist1/PGC-1α/PPARα Signaling Pathway Pharmaceuticals heart failure Twist homolog 1 (Twist1) ginsenoside Rb<sub>1</sub> myocardial energy metabolism disorder |
| title | Ginsenoside Rb<sub>1</sub> Ameliorates Heart Failure Ventricular Remodeling by Regulating the Twist1/PGC-1α/PPARα Signaling Pathway |
| title_full | Ginsenoside Rb<sub>1</sub> Ameliorates Heart Failure Ventricular Remodeling by Regulating the Twist1/PGC-1α/PPARα Signaling Pathway |
| title_fullStr | Ginsenoside Rb<sub>1</sub> Ameliorates Heart Failure Ventricular Remodeling by Regulating the Twist1/PGC-1α/PPARα Signaling Pathway |
| title_full_unstemmed | Ginsenoside Rb<sub>1</sub> Ameliorates Heart Failure Ventricular Remodeling by Regulating the Twist1/PGC-1α/PPARα Signaling Pathway |
| title_short | Ginsenoside Rb<sub>1</sub> Ameliorates Heart Failure Ventricular Remodeling by Regulating the Twist1/PGC-1α/PPARα Signaling Pathway |
| title_sort | ginsenoside rb sub 1 sub ameliorates heart failure ventricular remodeling by regulating the twist1 pgc 1α pparα signaling pathway |
| topic | heart failure Twist homolog 1 (Twist1) ginsenoside Rb<sub>1</sub> myocardial energy metabolism disorder |
| url | https://www.mdpi.com/1424-8247/18/4/500 |
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