Ginsenoside Rg1 Prevents Doxorubicin-Induced Cardiotoxicity through the Inhibition of Autophagy and Endoplasmic Reticulum Stress in Mice

Figures

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  Figure 1. (A) Chemical structures of ginsenoside Rg1. (B) Schedule of the experiments. The mice received four doses of doxorubicin (6 mg/kg) or PBS every 3 d, as indicated. (C) Representative echocardiography images of left ventricle, (D) Echocardiographic measurement of EF (ejection fraction), (E) Echocardiographic measurement of fractional shortening (FS). ## p < 0.01 vs C group, ** p < 0.01 vs. DOX group.

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  Figure 2. Protective effects of ginsenoside Rg1 on cardiac morphology and fibrosis in doxorubicin-induced cardiomyopathy. The upper panel represents images with H&E staining; the lower panel indicates cardiac fibrosis with Masson′s Trichrome staining. Scale bar: 100 μm.

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  Figure 3. Rg1 inhibits autophagy in the hearts of mice. (A) Electron microscope images of autophagosome (indicated by arrow, 50,000×) from three groups. (B) Expression of LC3, ATG5 and P62 protein in mouse heart. GAPDH was used as the loading control. # p < 0.05, ## p < 0.01 vs C group, * p < 0.05, ** p < 0.01 vs DOX group.

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  Figure 4. The anti-endoplasmic reticulum stress effects of Rg1 in mice heart. (A) Electron microscope images of ER (indicated by arrow, 50,000×) from three groups. (B) Expression of ATF6, Cleaved ATF6, IRE1, XBP1s, XBP1u and GFAT1 protein in mouse heart. GAPDH was used as the loading control. # p < 0.05, ## p < 0.01 vs. C group, * p < 0.05, ** p < 0.01 vs DOX group.

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  Figure 5. The mechanisms of Rg1 to improve endoplasmic reticulum stress. (A) Expression of TIF1, GRP78 and HRD1 protein in mouse heart. (B) Expression of Pre-rRNA level in mouse heart, GAPDH was used as the loading control. # p < 0.05, ## p < 0.01 vs C group, * p < 0.05 vs DOX group.

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  Figure 6. Effect of Rg1 on the autophagic pathway activated by endoplasmic reticulum stress in mice heart. (A) Expression of p-P70S6K, P70S6K, JNK1 and Beclin1 protein in mouse heart. (B) Expression of FAM134B protein in mouse heart, GAPDH was used as the loading control. # p < 0.05, ## p < 0.01 vs C group, * p < 0.05, ** p < 0.01 vs. DOX group.

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  Figure 7. Schematic diagram of how ginsenoside Rg1 attenuates doxorubicin-induced cardiomyotoxicity through the inhibition of autophagy and endoplasmic reticulum stress in mice.