Injection of YiQiFuMai powder protects against heart failure via inhibiting p38 and ERK1/2 MAPKs activation

Figures

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  Figure 1.. Identification of main components in 20190314 batches of YQFM. (1) Ginsenoside Re; (2) ginsenoside Rg1; (3) ginsenoside Rf; (4) ginsenoside Rb1; (5) notoginsenoside R2; (6) ginsenoside F3; (7) ginsenoside Rc; (8) ginsenoside Rg2; (9) ginsenoside Rb2; (10) ginsenoside Rg2; (11) ginsenoside Ro; (12) ginsenoside Rb3; (13) 20(S)-ginsenoside Rh1; (14) (20S)-ginsenoside Rd; (15) ginsenoside Rg6; (16) 20(s)-ginsenoside F2; (17) schizandrin A; (18) ginsenoside Rh4; (19) taiwanschirin D; (20) angeloylgomisin Q; (21) ginsenoside Rg3; (22) schizandrol B; (23) tigloylgomisin H; (24) ginsenoside Rk1; (25) ginsenoside Rg5; (26) alpha-linolenic acid; (27) conjugated linoleic acid.

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  Figure 2.. Kinases complying with inhibition rates ≥40 shown on the human kinome dendrogram. The top kinases inhibited by YQFM were determined using the KinaseProfiler of DiscoverX (red triangle). The 39 kinase-disease association therapeutic area of cardiovascular disease were developed by built-in data Sources of KinMap (OrangeRed circle). The figure was generated by using an online KinMap program (http://kinhub.org/kinmap/).

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  Figure 3.. Effects of YQFM on MAPKs signalling cascades in H9c2 cardiomyocytes. (A) Representative Western blotting images of activation status of three major branches of MAPKs in H9c2 cardiomyocytes treatment with increasing concentrations of YQFM, and p38 inhibitors SB203580. (B) Immunofluorescence staining demonstrating the effects of 2 mg/mL YQFM on P-p38 MAPK, P-ERK1/2, p38 and ERK1/2 expression in H9c2 cardiomyocytes. Scale bars = 30–50 μm.

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  Figure 4.. Echocardiogram analysis showing YQFM improvement of LV function in HFrEF rats. Serial echocardiographic measurements of (A) Left ventricular volume at end-diastole, (B) left ventricular volume at end-systolic, (D) left ventricular internal diameter at end-diastole and (E) left ventricular internal diameter at end-systole in the sham, control and YQFM group rat hearts before and after treatment. LV echocardiogram parameters included (C) ejection fraction (EF) and (F) fractional shortening (FS) were calculated as indicated (sham n ≥ 8, model n ≥ 17, YQFM n ≥ 8). Data are indicated as mean ± SD, ***p < 0.0001, **p < 0.01, *p < 0.05 and nsp > 0.05.

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  Figure 5.. Effects of YQFM on MAPKs signalling cascades in rats with HFrEF induced by LAD permanent ligation. (A) Immunofluorescence staining demonstrating P-p38 and P-ERK1/2 expression and localization in sham, control and YQFM group hearts. Western blotting images (B) and quantitative densitometry analysis of P-p38/p38 (C), P-ERK1/2/ERK1/2 (D), P-JNK/JNK (E), MEK3/6 normalized to GAPDH (F), MEK1/2 normalized to GAPDH (G) and MEK5 normalized to GAPDH (H) from LV tissue homogenates in HFrEF rats; n = 3 per group. Data are indicated as mean ± SD, ***p < 0.0001, **p < 0.01, *p < 0.05 and nsp > 0.05.

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  Figure 6.. Effects of YQFM on cardiac fibrosis in rats with HFrEF. (A) Representative H&E-stained and Masson-stained whole-heart images of sham, control and YQFM group hearts at day 56 after surgery (scale bars = 1000 μm). (B) Fibrosis area (%) of sham, control and YQFM group hearts at day 56 after surgery (sham n = 8, model n = 12, YQFM n = 8; data are indicated as mean ± SD).