Qingda granule prevents obesity-induced hypertension and cardiac dysfunction by inhibiting adverse Akt signaling activation

Figures

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  Figure 1. QDG attenuates HFFD-induced blood pressure elevation. (A) Changes in bodyweight over time in HFFD-fed mice administered with saline, QDG-L or QDG-H. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001 for HFFD vs. Normal Diet group, #p < 0.05, ##p < 0.01, ###p < 0.001 for HFFD + QDG-L vs. Normal Diet group, †p < 0.05, ††p < 0.01, †††p < 0.001 for HFFD + QDG-H vs. Normal Diet group, n.s., no significance. Normal Diet, n = 17; HFFD, n = 18; HFFD + QDG-L, n = 12; HFFD + QDG-H, n = 12. Complete list of statistical analyses are detailed in Supplementary Table 1. (B–D) Changes in blood pressures over time in HFFD-fed mice administered with saline, QDG-L or QDG-H, including systolic blood pressure (SBP) (B), diastolic blood pressure (DBP) (C), and mean arterial blood pressure (MAP) (D). ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001 for Normal Diet group vs. HFFD, #p < 0.05, ##p < 0.01, ###p < 0.001 for HFFD + QDG-L vs. HFFD, †p < 0.05, ††p < 0.01, †††p < 0.001 for HFFD + QDG-H vs. HFFD, n.s., no significance. Data are presented as mean ± sem. Normal Diet, n = 12; HFFD, n = 10; HFFD + QDG-L, n = 13; HFFD + QDG-H, n = 13. Complete list of statistical analyses are detailed in Supplementary Table 1. (E–G) Peak blood…

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  Figure 2. QDG prevents HFFD-induced cardiac dysfunction. (A–D) Echocardiography assessment of cardiac function in mice administered with saline, QDG-L or QDG-H following induction of HFFD for 16 weeks, with ejection fraction (EF%) (A), fractional shortening (FS%) (B) parameters, representative M-mode echocardiographic images of LV end-systolic and end-diastolic dimensions (C), and summary table of cardiac function measurements (D). ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001. Data are presented as mean ± sem. Normal Diet, n = 15; HFFD, n = 13; HFFD + QDG-L, n = 13; HFFD + QDG-H, n = 13. Complete list of statistical analyses are detailed in Supplementary Table 1. LVID; d, left ventricular internal dimension; diastolic; LVID; s, left ventricular internal dimension.

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  Figure 3. QDG prevents HFFD-induced cardiac hypertrophy. (A) Heart weight/tibia length ratio (HW:TL) in mice administrated with saline, QDG-L or QDG-H following induction of HFFD for 16 weeks. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001. Data are presented as mean ± sem. Normal Diet, n = 11; HFFD, n = 6; HFFD + QDG-L, n = 4; HFFD + QDG-H, n = 4. Complete list of statistical analyses are detailed in Supplementary Table 1. (B–C) Echocardiography assessment of heart LV wall thickness in mice administered with saline, QDG-L or QDG-H following induction of HFFD for 16 weeks, showing interventricular septum thickness (IVS) (B) and LV posterior wall thickness (LVPW) (C) parameters. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001. Data are presented as mean ± sem. Normal Diet, n = 15; HFFD, n = 13; HFFD + QDG-L, n = 13; HFFD + QDG-H, n = 13. Complete list of statistical analyses are detailed in Supplementary Table 1. (D–E) Representative H&E images (D) and quantification of cardiomyocyte cross-sectional area (E) of hearts in mice administered with saline, QDG-L or QDG-H following induction of HFFD for 16 weeks. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001. Data are presented as mean ± sem. Normal Diet, n = 5; HFFD, n = 6;…

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  Figure 4. QDG inhibits adverse activation of Akt signaling pathway during long-term HFFD induction. (A–C) Representatives immunoblots (A) and quantification (B–C) showing expressions of β-MHC/α-MHC and Collagen I levels in mice administrated with saline, QDG-L or QDG-H following induction of HFFD for 16 weeks. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001. n = 3 for each group. Raw uncropped images are shown in Supplementary Material 1.(D) Real-time PCR analysis showing relative mRNA expression of GDF15 in heart tissue after 16 weeks of HFFD diet induction. β-actin was used as the loading control. Data are presented as mean ± sem. ∗p < 0.05, ∗∗∗p < 0.001. Normal Diet, n = 4; HFFD, n = 6; HFFD + QDG-L, n = 6; HFFD + QDG-H, n = 7. Complete list of statistical analyses are detailed in Supplementary Table 1. (E–F) Representatives immunoblots (E) and quantification (F) showing expressions of p-Akt/Ak levels in mice administrated with saline, QDG-L or QDG-H following induction of HFFD for 16 weeks. β-actin was used as the loading control. Data are presented as mean ± sem. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001. n = 3 for each group. Raw uncropped images are shown in Supplementary Material 1.

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  Figure 5. Long-term use of QDG has no observable side effects. (A) Representative images in mice administrated with saline, QDG-L or QDG-H following induction of HFFD for 16 weeks. (B–C) Muscle weight (B) and grip strength (C) in mice administrated with saline, QDG-L or QDG-H following induction of HFFD for 16 weeks. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001. Data are presented as mean ± sem. Normal Diet, n = 15; HFFD, n = 14; HFFD + QDG-L, n = 13; HFFD + QDG-H, n = 13. Complete list of statistical analyses are detailed in Supplementary Table 1. (D–H) Fat weight (D), and serum triglycerides (TG) (E), total cholesterol (TC) (F), low density lipoprotein cholesterol (LDL-C) (G), high-density lipoprotein cholesterol (HDL-C) (H) in mice administrated with saline, QDG-L or QDG-H following induction of HFFD for 16 weeks. n.s., no significance, ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001. Data are presented as mean ± sem. Normal Diet, n = 11; HFFD, n = 10; HFFD + QDG-L, n = 10; HFFD + QDG-H, n = 13. Complete list of statistical analyses are detailed in Supplementary Table 1. (I–K) Mean daily food intake (I), water intake (J) and fasted blood glucose levels (K) in mice administrated with saline, QDG-L or QDG-H…

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  Figure 6. QDG prevents obesity-induced organ damage. (A–D) Serum biochemical liver function markers Alanine aminotransferase (ALT) (A), aspartate transaminase (AST) (B), and kidney function markers blood urine nitrogen (BUN) (C) and creatinine (D) in mice administrated with saline, QDG-L or QDG-H following induction of HFFD for 16 weeks. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001. Data are presented as mean ± sem. Normal Diet, n = 10; HFFD, n = 19; HFFD + QDG-L, n = 10; HFFD + QDG-H, n = 12. Complete list of statistical analyses are detailed in Supplementary Table 1.