The role of Nrf2 in astragaloside IV-mediated antioxidative protection on heart failure.

CONTEXT: Heart failure is one of the most serious diseases worldwide. Astragaloside IV (ASI) is widely used in the treatment of cardiovascular diseases. OBJECTIVE: To elucidate the antioxidative mechanism of ASI in a rat model of left coronary artery ligation. MATERIALS AND METHODS: Left coronary artery of Sprague-Dawley rats was ligated to establish the model of heart failure, and then vehicle (saline) or ASI (1 mg/kg/day) was orally administered to the rats (n = 15) for 6 weeks. Echocardiography was used to evaluate the cardiac function. Myocardial infarct size was measured by triphenyltetrazolium chloride staining. Oxidative stress in the ventricular myocardium was determined. Molecular mechanisms were investigated by Western blot and chromatin immunoprecipitation. RESULTS: ASI improved the cardiac function, especially ejection fraction (75.27 ± 5.75% vs. 36.26 ± 4.14%) and fractional shortening (45.39 ± 3.66% vs. 17.88 ± 1.32%), and reduced the infarct size of left ventricle (20.69 ± 2.98% vs. 39.11 ± 3.97%). ASI maintained the levels of glutathione, catalase and superoxide dismutase and prevented the leakage of creatine kinase. In addition, ASI induced the protein expression of Nrf2 (1.97-fold) and HO-1 (2.79-fold), while reduced that of Keap-1 (0.77-fold) in the ventricular myocardium. In H9c2 cells, a rat cardiomyocyte cell line, ASI induced the translocation of Nrf2 from cytoplasm to nucleus, followed by transcriptional activation of NQO-1 (8.27-fold), SOD-2 (3.27-fold) and Txn-1 (9.83-fold) genes. DISCUSSION AND CONCLUSIONS: ASI prevented heart failure by counteracting oxidative stress through the Nrf2/HO-1 pathway. Application in clinical practice warrants further investigation.

Preclinical study of Shen Qi Li Xin formula in improving the development of chronic heart failure.

Chronic heart failure (CHF) is a common clinical heart disease. In recent years, traditional Chinese medicines have shown good outcomes in CHF treatment. We aimed to explore the therapeutic effect of Shen Qi Li Xin formula (SQLXF) in CHF. CHF rats were treated with SQLXF at the doses of 8.48, 16.96, and 33.92 g/kg/d once a day for 4 weeks by intragastric administration. The hemodynamic and cardiac function parameters of the rats were monitored by conduction echocardiography. In our results, SQLXF treatment at the doses of 16.96 and 33.92 g/kg/d significantly improved the haemodynamics and cardiac function of CHF rats by enhancing the levels of LVSP, +dp/dtmax, -dp/dtmax, LVEF and LVFS and reducing the levels of LVEDP, LVEDD and LVESD. SQLXF treatment at 16.96 and 33.92 g/kg/d also attenuated the damage of myocardial tissues in CHF rats. In addition, compared with normal rats, the number of pericytes was reduced in myocardial tissues of CHF rats. SQLXF treatment at the doses of 16.96 and 33.92 g/kg/d obviously increased the number of pericytes and proliferation of endothelial cells and promoted angiogenesis in myocardial tissues of CHF rats. In vitro, SQLXF impaired low-oxygen-induced inhibition of cell viability and promotion of apoptosis in primary pericytes. Importantly, SQLXF enhanced the adhesion ability of pericytes to endothelial cells. In conclusion, SQLXF improved myocardial injury in CHF rats by enhancing the interaction between pericytes and endothelial cells, suggesting that SQLXF may be a potential drug for CHF treatment.

A self-calibrated luminescent thermometer based on nanodiamond-Eu/Tb hybrid materials.

Luminescent hybrid materials based on nanodiamonds (NDs) and rare earth ions have been successfully synthesized by covalently modifying NDs with pyromellitic acid (PMA) which is capable of coordinating to Eu3+ and Tb3+ ions. With NDs acting as a host matrix, the PMA and rare earth ions serve as an organic sensitizer and activator, respectively, yielding a highly bright hybrid composite. Interestingly, for the co-doped hybrid composites ND-PMA-Eu/Tb, the intensity ratio of the two emissions, 5D4→7F5 transition (Tb3+) to 5D0→7F2 transition (Eu3+), is linearly related to temperature in the range from 77 K to 277 K. Therefore, the hybrid could be developed as a self-calibrated ratiometric luminescent thermometer due to its temperature-dependent luminescence performance.