Antihypertensive Effects of Diosmetin in Hypertension-Induced Cardiovascular Abnormalities in Rats

Figures

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  Figure 1. Chemical structure of diosmetin.

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  Figure 2. Experimental designs of the study. 2K-1C; two-kidney, one clip, DT20; diosmetin (20 mg/kg), DT40; diosmetin (40 mg/kg), T5; telmisartan (5 mg/kg).

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  Figure 3. Systolic blood pressure (SBP) in all groups. The data are expressed as mean ± SEMs. 2K-1C; two-kidney, one clip, DT20; diosmetin (20 mg/kg), DT40; diosmetin (40 mg/kg), T5; telmisartan (5 mg/kg). *p< 0.05 versus Sham + Vehicle, # p< 0.05 versus 2K-1C + Vehicle, † p< 0.05 versus 2K-1C + DT20, ‡ p< 0.05 versus 2K-1C + DT40.

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  Figure 4. The vasoconstriction responses to an electrical field stimulation (A) and norepinephrine (B) in the mesenteric bed of all experimental groups. The results are depicted as mean ± SEMs. 2K-1C, two-kidney, one clip; DT20, diosmetin (20 mg/kg); DT40, diosmetin (40 mg/kg); T5, telmisartan (5mg/kg). * p< 0.05 versus Sham + Vehicle, # p< 0.05 versus 2K-1C + Vehicle, †p< 0.05 versus 2K-1C + DT20.

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  Figure 5. The responses to acetylcholine (A) and sodium nitroprusside (B) in the mesenteric bed and acetylcholine (C) and sodium nitroprusside (D) in aortic rings. The data are expressed as mean ± SEMs. 2K-1C, two-kidney, one clip; DT20, diosmetin (20 mg/kg); DT40, diosmetin (40 mg/kg); T5, telmisartan (5mg/kg). * p< 0.05 versus Sham + Vehicle, # p< 0.05 versus 2K-1C + Vehicle, †p< 0.05 versus 2K-1C + DT20.

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  Figure 6. Representative image of cardiac tissue stained with H&E (Double-headed arrow indicates cardiac wall thickness in all groups of experiments) (A). The semiquantitative assessment of cardiac remodeling is shown by left ventricular wall thickness (B), cross-sectional areas (C), and LV luminal areas (D). The data are expressed as mean ± SEMs. 2K-1C, two-kidney, one clip; DT20, diosmetin (20 mg/kg); DT40, diosmetin (40 mg/kg); T5, telmisartan (5mg/kg). * p< 0.05 versus Sham + Vehicle, #p< 0.05 versus 2K-1C + Vehicle, †p< 0.05 versus 2K-1C + DT20.

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  Figure 7. Representative figure of aortic section stain with H&E (Double-headed arrow indicates vascular wall thickness in all groups of experiments) (A). The quantitative analysis of vascular remodeling is indicated by wall thickness (B), cross-sectional areas (C), luminal diameter (D), and wall/lumen ratio (E). The data are expressed as mean ± SEMs. 2K-1C, two-kidney, one clip; DT20, diosmetin (20 mg/kg); DT40, diosmetin (40 mg/kg); T5, telmisartan (5mg/kg). * p< 0.05 versus Sham + Vehicle, # p< 0.05 versus 2K-1C + Vehicle, †p< 0.05 versus 2K-1C + DT20.

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  Figure 8. Serum angiotensin-converting enzyme (ACE) activity (A), plasma angiotensin II (Ang II) levels (B), and plasma angiotensin 1–7 (Ang-(1-7)) levels (C). The data are expressed as mean ± SEMs. 2K-1C, two-kidney, one clip; DT20, diosmetin (20 mg/kg); DT40, diosmetin (40 mg/kg); T5, telmisartan (5mg/kg). * p< 0.05 versus Sham + Vehicle, # p< 0.05 versus 2K-1C + Vehicle, †p< 0.05 versus 2K-1C + DT20.

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  Figure 9. Effects of diosmetin or telmisartan on O2•- production in the vascular (A), heart (B), kidney (C), and plasma malondialdehyde (MDA) levels (D). Levels of plasma catalase (CAT) activity (E) in all groups of rats. The data are expressed as mean ± SEMs. 2K-1C, two-kidney, one clip; DT20, diosmetin (20 mg/kg); DT40, diosmetin (40 mg/kg); T5, telmisartan (5mg/kg). * p< 0.05 versus Sham + Vehicle, # p< 0.05 versus 2K-1C + Vehicle, †p< 0.05 versus 2K-1C + DT20.

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  Figure 10. Representative Western blot images of membranes detected with chemiluminescence (A). Effects of diosmetin or telmisartan on AT1R (B), TGF-β (C), and MasR (D) protein expression in cardiac tissue collected from 2K-1C hypertensive rats. The data are expressed as mean ± SEMs. 2K-1C, two-kidney, one clip; DT20, diosmetin (20 mg/kg); DT40, diosmetin (40 mg/kg); T5, telmisartan (5 mg/kg). * p< 0.05 versus Sham + Vehicle, # p< 0.05 versus 2K-1C + Vehicle, †p< 0.05 versus 2K-1C + DT20.

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  Figure 11. Representative Western blot images of membranes detected with chemiluminescence (A). Effects of diosmetin or telmisartan on AT1R (B), TGF-β (C), and MasR (D) protein expression in aorta tissue collected from all groups. The data are expressed as mean ± SEMs. 2K-1C, two-kidney, one clip; DT20, diosmetin (20 mg/kg); DT40, diosmetin (40 mg/kg); T5, telmisartan (5mg/kg). * p< 0.05 versus Sham + Vehicle, # p< 0.05 versus 2K-1C + Vehicle, †p< 0.05 versus 2K-1C + DT20.

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  Figure 12. Molecular interactions between diosmetin and human ACE (PDB ID: 1UZE). (A) Superimposition of the docking pose of diosmetin and the crystallographic pose of enalaprilat at the catalytic domain. (B) Three-dimensional visualization of diosmetin binding at the active site. (C) Two-dimensional diagram summarizing key molecular interactions. (D) Heatmap comparing binding interactions of diosmetin and enalaprilat, with residues shown as columns and compounds as rows; dot size and color indicate interaction strength.