Related Experiment Video
Updated: May 10, 2025
In Vivo Detection and Analysis of Rb Protein SUMOylation in Human Cells
Published on: November 2, 2017
Ginsenoside Rb1 Ameliorates Heart Failure Ventricular Remodeling by Regulating the Twist1/PGC-1α/PPARα Signaling
Ziwei Zhou1, Zhimin Song1, Xiaomeng Guo1
1School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China.
Insights
Ginsenoside Rb1 improves heart failure (HF) by regulating the Twist1/PGC-1α/PPARα pathway, reducing fibrosis and restoring energy metabolism. This natural compound offers new therapeutic insights for HF treatment.
Area of Science:
- Cardiovascular Disease Research
- Molecular Mechanisms of Heart Failure
- Natural Product Therapeutics
Background:
- Heart failure (HF) is a severe cardiovascular condition with high mortality, inadequately addressed by current treatments.
- Myocardial fibrosis and impaired energy metabolism characterize ventricular remodeling in HF.
- Ginsenoside Rb1 shows anti-fibrotic potential, but its mechanism in HF requires elucidation.
Purpose of the Study:
- To investigate the underlying mechanisms of ginsenoside Rb1's therapeutic effects in heart failure.
- To explore the role of ginsenoside Rb1 in regulating the Twist1/PGC-1α/PPARα signaling pathway.
- To assess ginsenoside Rb1's impact on energy metabolism and ventricular remodeling in HF models.
Main Methods:
- Established a rat model of heart failure via coronary artery ligation, followed by ginsenoside Rb1 treatment.
- Evaluated cardiac function, myocardial histology, mitochondrial morphology, and energy metabolism markers.
- Utilized an in vitro H9c2 cell model to confirm ginsenoside Rb1's effects on the Twist1/PGC-1α/PPARα pathway.
Main Results:
- Ginsenoside Rb1 treatment restored cardiac function, improved mitochondrial efficiency, and alleviated energy metabolism disorders in HF rats.
- The compound modulated the Twist1/PGC-1α/PPARα pathway by suppressing Twist1 overexpression and normalizing PGC-1α and PPARα levels.
- In vitro studies confirmed that ginsenoside Rb1 inhibited Twist1 and promoted PGC-1α/PPARα expression in HF cardiomyocytes.
Conclusions:
- Ginsenoside Rb1 alleviates ventricular remodeling and improves myocardial energy metabolism in heart failure by modulating the Twist1/PGC-1α/PPARα pathway.
- Twist1 emerges as a potential key therapeutic target for heart failure treatment.
- This study provides novel insights into the clinical application of ginsenoside Rb1 for managing heart failure.
Abstract:
Background: 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 Rb1 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 Rb1's anti-HF mechanisms through the regulation of ginsenoside Rb1 on these metabolic regulators. Methods: Sprague Dawley rats were subjected to a ligation of the left anterior descending coronary artery to induce an HF model, followed by ginsenoside Rb1 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 Rb1's regulatory effects on the Twist1/PGC-1α/PPARα signaling pathway. Results: Ginsenoside Rb1 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 Rb1 suppressed the abnormal overexpression of Twist1 and maintained normal expression of downstream PGC-1α and PPARα. In vitro experiments further demonstrated that ginsenoside Rb1 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. Conclusions: Ginsenoside Rb1 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 Rb1 alleviates HF, but also provides new insights into the clinical treatment of HF.
