hyperoside and Myocardial-Infarction

Topics: Animals; Brain Infarction; Calcium Channel Blockers; Drugs, Chinese Herbal; Free Radical Scavengers; Myocardial Infarction; Phytotherapy; Plants, Medicinal; Quercetin

The genus Hypericum are widely distributed in China. Hypericum perforatum L. (genus Hypericum, family Hypericaceae) has a long history as a traditional Chinese medicine, which was traditionally used for the treatment of emotional distress, cardiothoracic depression, and acute mastitis. Hyperoside (Hyp) extracted from Hypericum perforatum L. has been affirmed to exert therapeutic effects on cardiovascular diseases, with widespread existence in plants of genus Hypericum. Hyp could also be extracted from Crataegus pinnatifida Bunge (genus Crataegus pinnatifida Bunge, family Rosaceae), another traditional Chinese medicine that traditionally prevented and treated heart disease in China. The cardioprotection and mechanism of Hyp comprise anti-inflammation, anti-fibrosis, activation of autophagy, and reversal of cardiac remodeling.. This study aimed to explore the Hyp effect against MI and its underlying mechanism.. The MI model was constructed in the KM mice via a ligating surgery of the left anterior descending (LAD) coronary artery. Subsequently, the mice were divided into following seven groups: Sham group, MI group, MI + Hyp 9 mg/kg group, MI + Hyp18 mg/kg group, MI + Hyp36 mg/kg group, MI + Fosinopril group, and MI + Hyp-36 mg/kg+3-MA group. Each group was treated with Hyp in different concentrations or positive medicine for two weeks except for the sham group. After two weeks, we examined the cardiac function, electrocardiogram (ECG), myocardial hypertrophy in the non-infarct area, collagen volume fraction (CVF), perivascular collagen area (PVCA) in the infarct area, and several serum cytokines. Autophagy and inflammation in cardiomyocytes were assessed via measuring autophagy-associated proteins and NLRP1 inflammasome pathway related proteins.. Hyp reversed LV remodeling and adverse ECG changes through reducing CVF and myocardial hypertrophy. Additionally, Hyp treatment could reduce inflammation levels in cardiomyocytes, compared with those in MI group. Moreover, NLRP1inflammation pathway was activated after MI. Up-regulation of autophagic flux suppressed NLRP1 inflammation pathway after Hyp treatment. However, co-treatment with 3-MA abrogated above effects of Hyp.. Hyp had obvious protective effect on heart injury in MI mice. Echocanrdiographic and histological measurements demonstrated that Hyp treatment improved cardiac function, and ameliorated myocardial hypertrophy and fibrinogen deposition after MI. The partial mechanism is that Hyp could up-regulate autophagy after MI. Furthermore, the promotion of autophagic flux would suppress NLRP1 inflammation pathway induced by MI.

Topics: Adaptor Proteins, Signal Transducing; Animals; Apoptosis Regulatory Proteins; Autophagy; Body Weight; Cardiotonic Agents; Cytokines; Disease Models, Animal; Electrocardiography; Heart Diseases; Hypericum; Inflammation; Male; Medicine, Chinese Traditional; Myocardial Infarction; Myocytes, Cardiac; Organ Size; Quercetin; Signal Transduction; Ventricular Remodeling

Role of hyperoside in protecting cardiomyocytes from ischemia/reperfusion induced injury has been proved. However, possible protecting mechanisms remain unclear. To fix the problem, an essential pro-apoptotic protein Bnip3 was studied in our experiments.. Neonatal rat cardiomyocytes were used and submitted to hypoxia for 8h followed by reoxygenation for 2h to simulate the ischemia/reperfusion injury. Hypoxia/reoxygenation(H/R) induced damage to cardiomyocytes and the protective effect of hyperoside were examined by means of MTT assay. H/R-induced apoptosis was assessed by Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling(TUNEL) and DNA Ladder assay. mRNA expression of Bnip3 was determined by use of quantitative real-time reverse transcription polymerase chain reaction assay. Protein levels of Bnip3, Bax, Bcl-2 and cleaved caspase-3 were examined using western-blot assay. Our results showed that H/R caused great damage to cardiomyocytes, upregulated the protein expressions of Bnip3, Bax, cleaved caspase3, and decreased the expression of the anti-apoptotic protein of Bcl-2. Whereas, compared with the H/R group, a decrease in activities of Bnip3, Bax, cleaved caspase3, and a promoting expression of Bcl-2 were detected in the H/R goup pretreated with hyperoside.. It was concluded in our study that H/R-induced apoptotic effect in cardiomyocytes could be attenuated by hyperoside, and the protective role of hyperoside, if not completely, could be partly through the suppression of the pro-apoptotic gene Bnip3.

Topics: Animals; Apoptosis; Cardiotonic Agents; Membrane Proteins; Mitochondrial Proteins; Myocardial Infarction; Myocytes, Cardiac; Plants, Medicinal; Quercetin; Rats; Rats, Sprague-Dawley; Reperfusion Injury

One of the leading causes of death in the world is ischemia/reperfusion (I/R)-mediated acute myocardial infarction. There are a lot of Chinese traditional patent medicines, such as Xin'an capsules, Xin Xuening tablets, and so on, which have protective effects against myocardial I/R injury and have been routinely used in treating cardiac diseases for a long time in China. Hyperoside (Hyp) is the chief component of these medicines. This study investigated the action of Hyp in isolated myocardial I/R injury, as well as its possible mechanisms. Using the Langendorff model, isolated Sprague-Dawley rat hearts were subjected to 30 min of global ischemia and 50 min of reperfusion. Cardiac function was measured, and infarct size was evaluated by triphenyltetrazolium chloride staining at the end of the reperfusion. Coronary effluent was analyzed for lactate dehydrogenase (LDH) and creatine kinase (CK). Myocardium was also measured for total superoxide dismutase (SOD) activity and malondialdehyde (MDA) content. Phosphorylation of extracellular signal-regulated protein kinase (ERK) was analyzed by Western blotting. We report for the first time that administration of Hyp before/after I/R significantly improved heart contraction and limited the infarct size and CK and LDH leakage from the damaged myocardium after I/R. The activity of SOD and the MDA content remarkably changed in the presence of Hyp as well. Phosphorylation of ERK was significantly increased in Hyp-treated hearts compared to controls (p<0.01). Hyp-induced ERK phosphorylation was inhibited by PD98059. We therefore conclude that Hyp can protect cardiomyocytes from I/R-induced oxidative stress through the activation of ERK-dependent signaling.

Topics: Animals; Cardiac Surgical Procedures; Caspase 3; Creatine Kinase; Flavonoids; L-Lactate Dehydrogenase; Male; Malondialdehyde; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Myocardial Contraction; Myocardial Infarction; Myocardial Reperfusion Injury; Myocytes, Cardiac; Oxidative Stress; Phosphorylation; Protein Kinase Inhibitors; Quercetin; Rats; Rats, Sprague-Dawley; Superoxide Dismutase