sapogenins and Myocardial-Infarction

Acute myocardial infarction (AMI) is an acute heart disease. Cycloastragenol, as a natural product, inhibits inflammation and protects cardiomyocytes. Cycloastragenol (Y006) modulates inflammation in AMI is not known. To explore the function of Cycloastragenol in AMI, this study investigated the effect of Y006 and its mechanisms both in vitro and in vivo. Y006 influences the concentration of 11 proteins, as shown by a proteomics analysis, immunohistochemistry and western blotting. Among these 11 proteins, Erk1/2, PLCG1, IKBKG, and ZEB1 are related to inflammatory regulation. BAX, COX2, and GSK3β are involved in modulating cardiomyocyte apoptosis, and RhoA and DSC2 are directly associated with myocardial function. However, the functions of ARHGAP17 and Rit2 in heart are less well established. Additionally, Y006 suppressed TNF-α, IFN-γ and IL-17 production in PBMCs (peripheral blood monocytes) from patients with acute myocardial infarction and enhanced IL-10 and IL-4 expression. Similar results were obtained in a rat model of AMI by flow cytometry detection and ELISA. Our findings indicate that Y006 protects rats from AMI through direct or indirect inhibition of inflammation and cardiomyocyte apoptosis. However, the specific mechanism of Y006's protective function requires further study. Nonetheless, this research revealed a novel aspect for the treatment of myocardial infarction. SIGNIFICANCE: In the present study, we undertook the first proteomic evaluation of Cycloastragenol (Y006) function in acute myocardial infarction (AMI). Y006 significantly improved myocardial function in vivo by regulating multiple molecular expressions. Hypoxia is a direct reason for AMI. And our data support a role of Y006 in gene expression, cell apoptosis under hypoxia. The conclusions of this research assist to explain the potential molecular mechanism in Cycloastragenol treating AMI and supply a new method for ameliorating AMI.

Topics: Animals; Apoptosis; Humans; I-kappa B Kinase; Monomeric GTP-Binding Proteins; Myocardial Infarction; Myocardium; Myocytes, Cardiac; Proteomics; Rats; Sapogenins

Clinical and experimental studies have established that gender is a factor in the development of ventricular hypertrophy. We investigated whether the attenuated hypertrophic effect of oestradiol was via activation of phosphatidylinositol 3-kinase (PI3K)/Akt/endothelial nitric oxide synthase (eNOS) through non-genomic action. Twenty-four hours after coronary ligation, female Wistar rats were randomized into control, subcutaneous oestradiol treatment or a G-protein coupled oestrogen receptor (GPER) agonist, G-1 and treated for 4 weeks starting from 2 weeks after bilateral ovariectomy. Ventricular hypertrophy assessed by cardiomyocyte size after infarction was similarly attenuated by oestradiol or G-1 in infarcted rats. The phosphorylation of Akt and eNOS was significantly decreased in infarcted rats and restored by oestradiol and G-1, implying the GPER pathway in this process. Oestradiol-induced Akt phosphorylation was not abrogated by G-15 (a GPER blocker). Akt activation was not inhibited by actinomycin D. When a membrane-impermeable oestrogen-albumin construct was applied, similar responses in terms of eNOS activation to those of oestradiol were achieved. Furthermore, PPT, an ERα receptor agonist, activated the phosphorylation of Akt and eNOS. Thus, membrane ERα receptor played a role in mediating the phosphorylation of Akt and eNOS. The specific PI3K inhibitor, LY290042, completely abolished Akt activation and eNOS phosphorylation in infarcted hearts treated with either oestradiol or oestradiol + G-15. These data support the conclusions that oestradiol improves ventricular remodelling by both GPER- and membrane-bound ERα-dependent mechanisms that converge into the PI3K/Akt/eNOS pathway, unveiling a novel mechanism by which oestradiol regulates pathological cardiomyocyte growth after infarction.

Topics: Animals; Blotting, Western; Cyclopentanes; Estradiol; Estrogen Receptor alpha; Estrogens; Female; Ginsenosides; Membrane Proteins; Myocardial Infarction; Nitric Oxide Synthase Type III; Ovariectomy; Phosphatidylinositol 3-Kinases; Phosphorylation; Proto-Oncogene Proteins c-akt; Quinolines; Random Allocation; Rats, Wistar; Receptors, G-Protein-Coupled; Sapogenins; Signal Transduction; Ventricular Remodeling

In this study, we investigated the cardioprotective effect of Panax quinquefolium 20(S)-protopanaxadiol saponins (PQDS) both in vivo and in vitro. An animal model of acute myocardial infarction was induced by permanent ligation of the left anterior descending coronary artery in Sparague Dawley rats. Neonatal rat cardiomycocytes were used to examine the cytoprotective effect of PQDS against H202 exposure. Pretreatment with PQDS (25 and 50 mg/kg) could significantly improve the heart function, remarkably decrease infarct size from 20.87% to 14.87% (p<0.01), decrease the levels of creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and cardiac troponin T (cTnT) content in serum (p< 0.05). Meanwhile, pretreatment with PQDS (25 and 50 mg/kg) significantly increased the activities of superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-Px) in the heart, and decreased the level of malondiadehyde (MDA) in the myocardium (p<0.05). Histopathological results demonstrated the same protective effect of PQDS. Pretreatment with PQDS (200 and 400 microg/ml) prior to H202 exposure could increase cell viability of neonatal rat cardiomycocytes. Pretreatment PQDS (200 and 400 microg/ml) also increased the activity of SOD, decreased level of LDH in the cultured supernatant and the MDA level in cardiomyocytes. These results indicated that PQDS had a cardioprotective effect proven in vivo and in vitro. The mechanisms might be due to its scavenging lipid peroxidation products, increasing endogenous antioxidant defense enzymes.

Topics: Animals; Animals, Newborn; Biomarkers; Cardiotonic Agents; Cells, Cultured; Coronary Occlusion; Electrocardiography; Female; Heart Function Tests; Hydrogen Peroxide; Indicators and Reagents; Male; Myocardial Infarction; Myocytes, Cardiac; Oxidants; Panax; Rats; Rats, Sprague-Dawley; Sapogenins; Survival

It was reported Panax ginseng had diverse components and multifaceted pharmacological functions. This study aims to investigate the effect of 20(S)-protopanaxatriol (PT, CAS 179799-20-3) and its epimeric derivatives (20S, 24R-epoxy-dammarane-3beta, 6alpha, 12beta, 25-tetraol, PTD1 and 20S, 24S-epoxy-dammarane-3beta, 6alpha, 12beta, 25-tetraol, PTD2) on myocardial injury induced by isoproterenol in rats.. Male Wistar rats were administered orally 20(S)-protopanaxatriol or its epimeric derivatives for 7 days. Four days after treatment, all rats, except those in the control group, were subcutaneously injected with isoproterenol (20 mg/kg) for 3 consecutive days. Two hours after the last isoproterenol injection, the rats were anaesthetized and sacrificed. The biochemical parameters were assayed and pathological examination of the heart tissues was performed.. Administration of PT and PTD1 resulted in a reduction in creatine kinase and lactate dehydrogenase. PT and PTD1 Inhibited not only the elevation of malondialdehyde content, but also the reduction of superoxide dismutase activity, glutathione peroxidase and total antioxIdant capacity. The pathohistological changes induced by isoproterenol were also ameliorated by PT and PTD1.. The present findings suggest that PT and PTD1 exerted cardioprotective effects against myocardial ischemic injury by enhancing the anti-free-radical actions of heart tissues. Furthermore the results indicated that the configuration of C-24 of the funan ring was involved in the phannacological action of the epimeric derivatives of 20(S)-protopanaxatriol.

Topics: Adrenergic beta-Agonists; Animals; Antioxidants; Cardiomyopathies; Creatine Kinase; Glutathione Peroxidase; Indicators and Reagents; Isoproterenol; L-Lactate Dehydrogenase; Lipid Peroxidation; Male; Malondialdehyde; Myocardial Infarction; Myocardium; Rats; Rats, Wistar; Sapogenins; Stereoisomerism; Superoxide Dismutase; X-Ray Diffraction