Ginsenoside Rb1 Ameliorates Heart Failure Ventricular Remodeling by Regulating the Twist1/PGC-1α/PPARα Signaling Pathway

Figures

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  Figure 1. Chemical structure of ginsenoside Rb1.

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  Figure 2. Ginsenoside Rb1 improves cardiac function and myocardial injury in rats with HF. (A) Weight and HWI of rats with HF. (B) Measurement of serum biochemical indicators ANP and BNP (n = 6). (C) Representative M-mode images of echocardiography. (D) Echocardiographic parameters of EF, FS, LVAW(d), LVAW(s), LVPW(d), LVPW(s), LVID(d), LVID(s), LV Vol(d), and LV Vol(s) (n = 5). Compared with the HF group, *** p < 0.001, ** p < 0.01, * p < 0.05. Sham: the sham group; HF: HF model group; HF + valsartan: valsartan treatment group (8 mg/kg); HF + Rb1-L: Rb1 treatment group (40 mg/kg); HF + Rb1-H: Rb1 treatment group (80 mg/kg).

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  Figure 3. Ginsenoside Rb1 can improve the pathological changes of the left ventricle in rats with HF. (A) Pictures of rat hearts. (B) Representative HE-stained myocardial tissue sections (n = 6). Bar = 20 µm (40× original magnification). The yellow arrow indicates the typical pathological changes of myocardial tissue. (C) Representative Masson-stained images of cardiac tissue sections (n = 6). Bar = 20 µm (40× original magnification). The yellow arrow indicates the typical pathological changes of myocardial tissue. (D) Observation on the ultrastructure of the hearts of rats with HF screened by a transmission electron microscope (n = 5). Bar = 2 µm or Bar = 500 nm (10,000× original magnification or 30,000× original magnification, the picture below the red dotted line is an enlargement of the picture above.).

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  Figure 4. Ginsenoside Rb1 can improve myocardial injury in rats with HF. (A) Evaluation of cTnT and ACTN2 expression of cardiac tissues on rats with HF using immunofluorescence. (n = 6). Bar = 20 µm (40× original magnification). (B) Evaluation of cTnT expression in the serum of rats with HF using ELISA method (n = 6). (C–E) Ginsenoside Rb1 regulated ATP content, ETC productivity efficiency, and MMP level in the heart tissue of rats with HF (n = 6). Compared with the HF group, *** p < 0.001, ** p < 0.01, * p < 0.05.

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  Figure 5. (A,B) Evaluation of GLUT4, PPARγ, Twist1, PGC-1α, and PPARα expression on rats with HF with a quantification of the average relative density of WB data. (C–E) Evaluation of Twist1, PGC-1α, and PPARα expression of cardiac tissues on rats with HF by immunohistochemistry. Compared with the HF group, *** p < 0.001, ** p < 0.01, * p < 0.05.

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  Figure 6. Detection of energy metabolism indexes of H9c2 cells: (A) Ginsenoside Rb1 regulated ATP content (n = 6), ETC productivity efficiency (n = 3), and MMP level (n = 3). (B) JC-1 mitochondrial membrane potential staining results. Compared with the ET-1 model group, *** p < 0.001, ** p < 0.01, * p < 0.05.

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  Figure 7. Expression of energy metabolism protein regulated by ginsenoside Rb1 in H9c2 cells was detected by ELISA: (A) Twist1, (B) PGC-1α, (C) PPARα (n = 6). Compared with the ET-1 model group, *** p < 0.001, ** p < 0.01, * p < 0.05.

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  Figure 8. Ginsenoside Rb1 and Twist1 (A) molecular docking results, (B) amino acid residues interaction.

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  Figure 9. Ginsenoside Rb1 alleviates ventricular remodeling in HF by regulating the Twist1/PGC-1α/PPARα signaling pathway. In the hearts of rats with HF, there is an increase in the expression of cTnT and ACTN2. Additionally, there is an elevation in atrial and ventricular pressures, accompanied by an increased secretion of ANP and BNP. Myocardial cell damage occurs, inhibiting glucose transport (reduced GLUT4 synthesis), leading to mitochondrial dysfunction. This dysfunction manifests as a decrease in MMP, reduced ATP synthesis, and decreased ETC productivity efficiency, resulting in disordered energy metabolism. Furthermore, an abnormally high expression of Twist1 is observed, which inhibits the expression of PGC-1α, PPARα, and PPARγ, thereby exacerbating cardiac injury.