cardiovascular-agents and puerarin

Topics: Animals; Biological Availability; Caco-2 Cells; Cardiovascular Agents; Diffusion; Disease Models, Animal; Humans; Hydrogen Bonding; Isoflavones; Isoproterenol; Male; Myocardial Ischemia; Nanoparticles; Particle Size; Rats; Rats, Sprague-Dawley; Solubility

Chinese patent medicine Zhixiong Capsule (ZXC) has been used in clinical treatment against blood stasis-induced dizziness and headache for many years in China.. Recent clinical observations demonstrated a good efficacy of ZXC against atherosclerotic plaque formation in carotid arteries. The aims of this study were to verify the plaque-preventing efficacy of ZXC in animals and to investigate the underlying mechanisms.. ZXC (185 mg/kg and 370 mg/kg) was administrated to rabbits which received collar implantation accompanied with high fat diet administration (12 days). The blood-dissolved components of ZXC were identified by an UPLC-QTOF-MS method. The key components and targets of ZXC were then predicted based on network pharmacology analysis and biological investigations.. Compared with vehicle control group, ZXC administration (185 mg/kg) significantly prevented plaque formation and attenuated intima thickening in the collar-implanted carotid arteries, markedly decreased blood lipid level, and increased plasma IL-4 level in rabbits. A total of 23 blood-dissolved components were identified. Four ingredients (namely, kaempferol, daidzein, puerarin, miltirone) along with leech, and three targets (namely, JUN, FOS and TP53) were recognized to play important roles for ZXC bioactivity.. It could be concluded that ZXC could be applied to prevent atherosclerotic plaque formation and intimal thickening in carotid arteries at the current clinical dose.

Topics: Animals; Cardiovascular Agents; Carotid Arteries; Interleukin-4; Isoflavones; Kaempferols; Leeches; Male; Medicine, Chinese Traditional; Plaque, Atherosclerotic; Rabbits

Puerarin is used to treat cardiovascular diseases due to its anti-inflammatory and antifibrotic effects. However, its mechanism of action in atrial fibroblasts is unknown. In this study, we investigated the autophagy pathway and molecular changes in angiotensin II (AngII)-stimulated atrial fibroblasts in response to puerarin treatment. Atrial fibroblasts were cultured and then subjected to stimulation with AngII and puerarin or other chemical drugs (3-MA, CQ, and SP600125). Quantitative real-time polymerase chain reaction and Western blot experiments were used to quantify the expression levels of mRNA and protein. mCherry-GFP-LC3 adenovirus was applied to reflect the autophagic flux. The results showed aggravating levels of autophagy and collagen deposit in the presence of AngII. Puerarin inhibited autophagy and decreased collagen secretion in a dose-dependent manner in atrial fibroblasts. Furthermore, phosphorylation of JNK was down-regulated in response to puerarin, whereas phosphorylation of Akt and mammalian target of rapamycin (mTOR) was upregulated. Interestingly, reduced autophagy and collagen secretion were observed when the JNK signaling pathway was blocked using SP600125. We also observed upregulation of Akt and mTOR phosphorylation in the presence of SP600125. These results suggest that puerarin exerts its antifibrotic effect in atrial fibroblasts partly through the inhibition of autophagy. Furthermore, the mechanism of action of puerarin in fibroblast autophagy seems to be mediated partly through JNK-Akt-mTOR signaling.

Topics: Angiotensin II; Animals; Autophagy; Cardiovascular Agents; Cells, Cultured; Collagen; Dose-Response Relationship, Drug; Fibroblasts; Fibrosis; Heart Atria; Isoflavones; JNK Mitogen-Activated Protein Kinases; Mice; Phosphorylation; Proto-Oncogene Proteins c-akt; Signal Transduction; Time Factors; TOR Serine-Threonine Kinases

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

Puerarin, an isoflavone compound, is an important ingredient in traditional Chinese medicine, which has the good medical effects on hypertension and angina. A new type of separation and purification method for isolating puerarin was developed using chelate complex chromatography. The stationary phase was prepared with silica gel containing 7% of Cu(OAc)2 in the chloroform. After the chloroform was evaporated, it was used as chelate complex chromatographic stationary phase to purify puerarin extractive. Pure puerarin was obtained when a mixture of chloroform and methanol (10:1, v/v) was used as eluent. In comparison with a common silica gel column, the chelate complex chromatographic column was more convenient and efficient. The purity and recovery of puerarin, and column capacity were improved 11%, 12% and 200%, respectively. Under the optimized experimental conditions, the purity of puerarin could be as high as with a recovery of 92%.

Topics: Cardiovascular Agents; Chromatography; Coordination Complexes; Copper; Drugs, Chinese Herbal; Isoflavones; Organometallic Compounds