hydroxysafflor-yellow-a and Heart-Failure

Heart failure (HF) is the terminal stage of all heart diseases that is characterized by irreversible cardiomyocyte injury. Equilibrium of autophagy is essential for cardiac cell survival. The Luhong formula (LHF) has been clinically applied for decades, and has exhibited significant efficacy in improving heart function and alleviating the symptoms of angina pectoris.. To clarify the mechanism of action of LHF and one of its main constituents, hydroxysafflor yellow A (HYSA), in protecting ischemic cardiomyocytes by inhibiting autophagy.. Cell viability was detected by CCK-8 assay with LHF or HYSA pretreatment followed by hypoxic damage. Immunofluorescence of GFP-LC3-H9C2 and GFP-LC3-HeLa cells was used to observe autophagic flux. Beclin 1 and HIF1α protein expression were assessed using western blotting. LHF was orally administered to Wistar rats following myocardial infarcion. Echocardiography was performed before the rats were sacrificed; immunohistochemistry and western blotting were used to evaluate Beclin 1 and HIF1α expression in the myocardial tissue. Hematoxylin and eosin staining as well as Masson's trichrome staining were used to measure cardiac structure and myocardial fibrosis.. LHF and HYSA reversed the hypoxia-induced decrease in cell viability in vitro. LHF and HYSA induced the aggregation of GFP-LC3 puncta and reduced the expression of Beclin 1 protein in H9C2, suggesting that LHF and HYSA may inhibit autophagy activity. Pretreatment with reactive oxygen species (ROS) inducers and inhibitors revealed that LHF and HYSA inhibited autophagy by suppressing cellular ROS. Further studies demonstrated that LHF and HYSA reduced the ROS levels by inhibiting HIF1α. LHF delayed fibrosis and protected heart function in vivo in a rat model of HF following myocardial infarction. Western blotting and immunohistochemistry revealed that LHF effectively reduced the expression of Beclin 1 and HIF1α in the infarcted area of the rat heart.. These results demonstrate that hydroxysafflor yellow A is the representative bioactive compounent of Luhong Formula on regulating autophagy to protectect cardiomyocytes from hypoxia injury. LHF and HYSA inhibit cardiac autophagy by suppressing HIF1α-mediated ROS production. This study helps to further clarify the underlying mechanism of LHF and provide a scientific basis for its development as a novel cardiovascular therapeutic agent.

Topics: Animals; Apoptosis; Autophagy; Beclin-1; Heart Failure; HeLa Cells; Humans; Hypoxia; Myocytes, Cardiac; Rats; Rats, Wistar; Reactive Oxygen Species

The present study was conducted to investigate whether hydroxysafflor yellow A (HSYA) has a protective effect on acute and chronic heart failure (AHF/CHF) induced by ligation of the left anterior descending coronary artery for 3 h and 8 weeks, respectively. The rats were divided into the following groups: sham operation, coronary artery ligation (CAL), CAL+HSYA (100 mg kg(-1) by gavage) and CAL+diltiazem (20 mg kg(-1) by gavage). In the AHF model, heart function, as determined by haemodynamic studies and echocardiography, was improved significantly by pretreatment with HSYA or diltiazem. Significant reductions in elevated serum creatine phosphokinase, lactate dehydrogenase, malondialdehyde (MDA), glutamic oxalacetic transaminase, glutamic pyruvic transaminase and blood viscosity were observed, and the activity of serum superoxide dismutase (SOD) was enhanced (all P<0.01). In the CHF model, HSYA and diltiazem restored abnormal heart function, and completely suppressed the elevated plasma atrial natriuretic polypeptide (ANP) and endothelin-1 (ET-1), serum and left-ventricular tissue inducible nitric oxide (NO) synthase (iNOS), NO and MDA, and improved the decrease in SOD. HSYA and diltiazem improved cardiac performance in AHF and reduced cardiac remodelling in CHF by reducing tissue weight indices: left ventricular weight/body weight (BW), right ventricular weight/BW, kidney weight/BW and lung weight/BW, and attenuating increases in infarct size, inner diameter of the left ventricle and collagen volume fraction in non-infarcted areas, and the decrease in mean wall thickness of infarcted myocardium. These results suggest that HSYA exerted beneficial actions in cardiac performance in models of both AHF and CHF, mainly by suppressing ET-1, iNOS and oxidative stress in infarcted tissue.

Topics: Acute Disease; Alanine Transaminase; Animals; Aspartate Aminotransferases; Blood Viscosity; Cardiotonic Agents; Chalcone; Chronic Disease; Coronary Vessels; Creatine Kinase; Diltiazem; Disease Models, Animal; Echocardiography; Endothelin-1; Heart Failure; Hemodynamics; L-Lactate Dehydrogenase; Ligation; Malondialdehyde; Nitric Oxide Synthase; Oxidative Stress; Quinones; Rats; Rats, Sprague-Dawley; Superoxide Dismutase