Danshenol A Alleviates Hypertension-Induced Cardiac Remodeling by Ameliorating Mitochondrial Dysfunction and Suppressing Reactive Oxygen Species Production

Figures

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  Figure 1. Effects of DA treatment on blood pressure and cardiac function during administration for 12 consecutive weeks: (a) SBP; (b) DBP; (c) MBP; (d) EF; (e) FS; (f) image of ultrasound cardiogram. n = 7. ###P < 0.001 vs. WKY, ##P < 0.01 vs. WKY, and #P < 0.05 vs. WKY; ∗∗∗P < 0.001 vs. SHR, ∗∗P < 0.01 vs. SHR, and ∗P < 0.05 vs. SHR.

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  Figure 2. Effect of DA treatment on the serum biochemical index at 12 weeks. (a) Cardiac function index including CK, CK-MB, and LDH; (b) hepatic function index including AST and ALT; (c) renal function index including Cr and BUN. ###P < 0.001 vs. WKY, ##P < 0.01 vs. WKY, and #P < 0.05 vs. WKY; ∗∗∗P < 0.001 vs. SHR, ∗∗P < 0.01 vs. SHR, and ∗P < 0.05 vs. SHR.

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  Figure 3. Effects of KXF treatment on cardiac remodeling. (a) Masson staining images under 200x magnification and the areas of collagen deposition were indicated by the black arrow; (b) HW/BW; (c) CVF. Results are presented as the mean ± SEM (∗P < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001 vs. SHR; ###P < 0.001 vs. WKY).

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  Figure 4. KEGG analysis of signaling pathways related to DA on cardiac remodeling. (a) Flow chart of reverse molecular docking using PharmMapper. (b) Significant enrichment of protein targets in the network diagram.

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  Figure 5. Changes in mitochondrial morphology and mitochondrial complex activity. (a) Ultrastructural analysis of myocardium under 8000x magnification and the areas of the mitochondrion were marked by the black arrow. (b–e) Maximal activities of complexes I-IV in cardiac mitochondria. ###P < 0.001 vs. WKY, ##P < 0.01 vs. WKY, and #P < 0.05 vs. WKY; ∗∗∗P < 0.001 vs. SHR, ∗∗P < 0.01 vs. SHR, and ∗P < 0.05 vs. SHR.

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  Figure 6. (a, b) ATP, ADP, and AMP concentrations and energy charge in the myocardium. (c–e) Oxidative stress indexes of MDA, ROS, and 4-HNE concentrations in the myocardium. ###P < 0.001 vs. WKY, ##P < 0.01 vs. WKY, and #P < 0.05 vs. WKY; ∗∗∗P < 0.001 vs. SHR, ∗∗P < 0.01 vs. SHR, and ∗P < 0.05 vs. SHR.

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  Figure 7. Effect of DA on cardiomyocyte apoptosis. (a, b) Ang II-induced cell apoptosis rate was quantified by flow cytometry. (c–e) Western blot analysis of apoptosis-related proteins: Bcl-2 and Bax in each groups. ###P < 0.001 vs. WKY, ##P < 0.01 vs. WKY, and #P < 0.05 vs. WKY; ∗∗∗P < 0.001 vs. SHR, ∗∗P < 0.01 vs. SHR, and ∗P < 0.05 vs. SHR.

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  Figure 8. Mechanism of DA ameliorates cardiac remodeling involved in mitochondrial redox signaling pathways in the myocardium. Protein expression of (a, b) p-Ras, Ras, p-Raf, and Raf; (c, d) p-Mek, Mek, p-Erk, and Erk; and (e, f) Ask1, p-Jnk, Jnk, p-p38, and p38 in the myocardium. Results are presented as the mean ± SEM (∗P < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001 vs. SHR; ∗P < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001 vs. Ang II; ###P < 0.001 vs. WKY and CON).

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  Figure 9. Mechanism of DA ameliorates cardiac remodeling involved in mitochondrial redox signaling pathways in cardiomyocytes. Protein expression of (a, b) p-Ras, Ras, p-Raf, and Raf; (c, d) p-Mek, Mek, p-Erk, and Erk; and (e, f) Ask1, p-Jnk, Jnk, p-p38, and p38 in cardiomyocytes. Results are presented as the mean ± SEM (∗P < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001 vs. SHR; ∗P < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001 vs. Ang II; ###P < 0.001 vs. WKY and CON).