Context: Heart failure (HF) is one of the most serious diseases worldwide. Astragaloside IV (ASI) is widely used for the treatment of cardiovascular disease in China. Objective: To evaluate the protective effect of ASI on the HF in a Sprague-Dawley rat model of left coronary artery ligation, and investigate the angiogenesis-related mechanisms. Materials and methods: Left coronary artery was ligated to induce a rat model of HF, and the rats were treated with vehicle (saline) or different doses of ASI (0.1, 0.3 and 1 mg/kg/day) by oral gavage for 6 weeks. Cardiac function was evaluated by echocardiography. Infarct size was determined by triphenyltetrazolium chloride staining. Cardiac vascular density was analyzed by microangiography. Real-time PCR, Western blot and chromatin immunoprecipitation were performed to investigate the mechanisms. Results: ASI treatment improved the body weight and survival rate of HF rats, as well as the cardiac function of HF rats, with significantly improved ejection fraction (75.27 ± 5.75% vs. 36.26 ± 4.14%) and fractional shortening (45.39 ± 3.66% vs. 17.88 ± 1.32%). ASI reduced the infarct size of the HF rats by 47%. ASI promoted angiogenesis, with increased vascular density (2.08fold) and induced mRNA expression of CD31 (1.81-fold) and VEGF (2.70-fold) in the ischemic heart. Furthermore, ASI induced the phosphorylation of JAK (1.89-fold) and STAT3 (2.95-fold), as well as the activity of VEGF promoter which was regulated by STAT3. Discussion and conclusions: ASI alleviated HF by promoting angiogenesis through JAK-STAT3 pathway, providing novel alternative strategies to prevent HF in the future.

This study retrospectively evaluated the effectiveness and safety of traditional Chinese medicine Shenqilixin Formula (SQLXF) as an adjunctive intervention for treating patients with chronic heart failure (CHF).This retrospective study included 135 patients with CHF. They were allocated to a treatment group or a control group according to the different treatments they received. Seventy five patients in the treatment group underwent SQLXF plus routine treatment, while 60 subjects in the control group received routine treatment only. The primary outcome was cardiac function. It was measured by the left ventricular end diastolic diameter (LVDD), left ventricular ejection fraction (LVEF), cardiac output (CO), every cardiac output (ECO), and cardiac index (CI). The secondary outcome included motor function. It was measured by the standard 6-MinuteWalk Test (6MWT). In addition, adverse events (AEs) were also recorded.Compared to subjects in the control group, patients in the treatment group revealed greater effectiveness in cardiac function, measured by LVEF (P < .05), CO (P < .05), and ECO (P < .05), and motor function, measured by the 6MWT scale (P < .05). Moreover, no significant differences of AEs were found between the 2 groups.SQLXF as an adjunctive therapy to routine treatment may help to improve both cardiac and motor function in patients with CHF.

Diabetes, a disease with high prevalence in China, is a major risk factor of cardiovascular disease. Hesperidin is a flavanone glycoside with anti-hyperglycemic and anti-hyperlipidemic activities. Therefore, the present study aimed to investigate the potential preventive effect of hesperidin against type 2 diabetes mellitus (T2DM) using a rat model of alloxan and high fat diet (HFD)-induced insulin resistance. Male Sprague Dawley rats were orally administered with 100 mg/kg hesperidin or vehicle (sodium carboxy methyl cellulose) for 35 days. Insulin resistance was induced by feeding animals a HFD for 3 weeks (from day 7) and then with an alloxan injection on day 28. Results from the in vivo study demonstrated that hesperidin improved fasting serum glucose (from 19.8 to 10.6 mmol/l) without changing the fasting insulin level, suggesting that hesperidin prevented the development of insulin resistance and diabetes by improving insulin sensitivity. In the oral glucose tolerance test, the development of impaired glucose tolerance was also prevented by hesperidin treatment. Hesperidin was found to regulate glycolysis and gluconeogenesis by enhancing the activity of glucokinase, inducing the phosphorylation of insulin receptor (IR) and phosphoinositide-dependent kinase 1 (PDK1), while decreasing the activity of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase in the liver. In a cell-based assay, hesperidin increased glucose uptake in primary rat adipocytes. Collectively, the present study identified the potent preventive effect of hesperidin against HFD-induced insulin resistance by activating the IR/PDK1 pathway. The current results may provide a potential strategy lacking sides effects to improve metabolic health and reduce risks.

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 ¼ 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.

Background Our previous study proved that Shen Qi Li Xin formula (SQLXF) improved the heart function of chronic heart failure (CHF) patients, while the action mechanism remains unclear. Methods H&E staining and TUNEL staining were performed to measure myocardial damages. Western blot was used to examine the expression of proteins. Moreover, CCK-8 assay and flow cytometry were used to measure cell viability and cell apoptosis, respectively. Concentrations of ATP and ROS in cells, and mitochondrial membrane potential (MMP) were detected to estimate oxidative stress. Results In vivo, we found that SQLXF improved cardiac hemodynamic parameters, reduced LDH, CK-MB and BNP production, and attenuated myocardial damages in CHF rats. Besides, SQLXF promoted mitochondrial fusion-related proteins expression and inhibited fission-related proteins expression in CHF rats and oxygen glucose deprivation/reoxygenation (OGD/R)-induced cardiac myocytes (CMs). In vitro, our data show that certain dose of SQLXF inhibited OGD/R-induced CMs apoptosis, cell viability decreasing and oxidative stress. Conclusion Overall, certain dose of SQLXF could effectively improve the cardiac function of CHF rats through inhibition of CMs apoptosis via balancing mitochondrial fission and fusion. Our data proved a novel action mechanism of SQLXF in CHF improvement, and provided a reference for clinical.