angiotensin-i and puerarin

Puerarin is an active ingredient of pueraria, which has been developed for puerarin injections, used in the treatment of cardiovascular diseases including arrhythmia, myocardial ischemia and hypertension. However, the molecular mechanisms of puerarin on ischemia/reperfusion (I/R)‑induced myocardial apoptosis in diabetic rats are not fully understood. The present study aimed to investigate whether puerarin can attenuate I/R‑induced myocardial apoptosis in diabetic rats, and to investigate the underlying mechanism. A hemodynamic analyzing system was employed to analyze the left ventricular developed pressure (LVDP), the left ventricular end‑systolic interior dimension (LVIDs) and the left ventricular end diastolic interior dimension (LVIDd). ELISA kits were used to analyze malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor‑α (TNF‑α) and interleukin (IL)‑6 levels, NO production and caspase‑3 activity. Nuclear factor (NF)‑κB, ascular endothelial growth factor A (VEGFA), angiotensin (Ang)‑I, phosphorylated (p)‑endothelial nitric oxide synthase protein expression was analyzed using western blot analysis. Puerarin significantly reduced the myocardial infarct area, and increased left ventricular developed pressure in diabetic rats with myocardial I/R. Oxidative stress, inflammation and nuclear factor‑κB protein expression were significantly reduced by puerarin. Furthermore, puerarin activated the protein expression levels of VEGFA and Ang‑I, and increased nitric oxide production, phosphorylated‑endothelial nitric oxide synthase protein expression and caspase‑3 activity. These results demonstrated that the myocardial protective effect of puerarin serves to reduce myocardial I/R injury, via upregulation of VEGFA/Ang‑1 and suppression of apoptosis, in diabetic rats with myocardial I/R.

Topics: Angiotensin I; Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Cardiovascular Agents; Diabetes Mellitus, Experimental; Isoflavones; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Oxidative Stress; Rats; Rats, Sprague-Dawley; Up-Regulation; Vascular Endothelial Growth Factor A; Vasodilator Agents

This study aimed to investigate the effect of combination of felodipine+puerarin on ACE2-Ang (1-7)-Mas axis, and to explore the protective effect of the combination against kidney in renovascular hypertensive rats. Goldblatt rats were randomly divided into 5 groups as follows: 4 groups which were treated with felodipine (Felo), puerarin (Pue), Felo+Pue, and Felo+captopril (Cap), respectively, and a control group of animals that were administrated with distilled water. Contents of Ang II and Ang (1-7) in renal tissues were determined by ELISA kit. The mRNA expression of ACE2/Mas and ACE/AT1 in kidneys was analyzed by RT-PCR. After 8weeks of treatment, compared with Goldblatt group, Felo+Pue reduced SBP, DBP and HR (p<0.01 or p<0.05), ameliorated renal interstitial fibrosis, decreased the level of Ang II and increased that of Ang (1-7), upregulated mRNA expression of ACE2 and Mas, decreased that of ACE and AT1, and downregulated protein expression of TGF-β1 in kidneys (p<0.01). Compared with Felo group, Felo+Pue decreased DBP and HR more markedly, attenuated fibrosis, decreased Ang II levels and increased those of Ang (1-7), upregulated mRNA expression of ACE2 in bilateral kidneys and that of Mas in ischemic kidney, downregulated that of ACE in bilateral kidneys and that of AT1 in ischemic kidney, and decreased expression of TGF-β1 protein significantly. In a word, a combination of Felo+Pue has a more efficient therapeutic effect on DBP and HR, and contributes to a better protection against renal interstitial fibrosis.

Topics: Angiotensin I; Angiotensin-Converting Enzyme 2; Animals; Drug Therapy, Combination; Felodipine; Hypertension, Renovascular; Isoflavones; Kidney; Peptide Fragments; Peptidyl-Dipeptidase A; Proto-Oncogene Mas; Proto-Oncogene Proteins; Rats; Rats, Sprague-Dawley; Receptors, G-Protein-Coupled; Vasodilator Agents