salvianolic-acid-a and Hypoxia

Topics: Actin Depolymerizing Factors; Caffeic Acids; Cell Movement; Cells, Cultured; Cytoskeleton; Endothelial Cells; Epithelial-Mesenchymal Transition; Humans; Hypoxia; Lactates; Mitogen-Activated Protein Kinases; Phosphorylation; Pulmonary Artery; Reactive Oxygen Species; Salvia miltiorrhiza; Smad1 Protein; Smad2 Protein

Salvianolic acid A (Sal A), a bioactive compound isolated from the Chinese medicinal herb Danshen, is used for the prevention and treatment of cardiovascular diseases. However, the protective function of Sal A on preserving the role of blood-spinal cord barrier (BSCB) after spinal cord injury (SCI) is unclear. The present study investigated the effects and mechanisms of Sal A (2.5, 5, 10mg/kg, i.p.) on BSCB permeability at different time-points after compressive SCI in rats. Compared to the SCI group, treatment with Sal A decreased the content of the Evans blue in the spinal cord tissue at 24h post-SCI. The expression levels of tight junction proteins and HO-1 were remarkably increased, and that of p-caveolin-1 protein was greatly decreased after SCI Sal A. The effect of Sal A on the expression level of ZO-1, occluding, and p-caveolin-1 after SCI was blocked by the HO-1 inhibitor, zinc protoporphyrin IX (ZnPP). Also, Sal A inhibited the level of apoptosis-related proteins and improved the motor function until 21days after SCI. In addition, Sal A significantly increased the expression of microRNA-101 (miR-101) in the RBMECs under hypoxia. AntagomiR-101 markedly increased the RBMECs permeability and the expression of the Cul3 protein by targeting with 3'-UTR of its mRNA. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and HO-1 was significantly increased after agomiR-101 treatment. Therefore, Sal A could improve the recovery of neurological function after SCI, which could be correlated with the repair of BSCB integrity by the miR-101/Cul3/Nrf2/HO-1 signaling pathway.

Topics: Animals; Caffeic Acids; Capillary Permeability; Cardiovascular Agents; Caveolin 1; Cullin Proteins; Disease Models, Animal; Drug Evaluation, Preclinical; Heme Oxygenase (Decyclizing); Hypoxia; Lactates; Male; MicroRNAs; Motor Activity; Neuroprotective Agents; NF-E2-Related Factor 2; Random Allocation; Rats, Sprague-Dawley; Spinal Cord; Spinal Cord Injuries; Tight Junctions; Zonula Occludens-1 Protein

Oxidative stress induced by overproduction of reactive oxygen species (ROS) plays an important role in hypoxia/reoxygenation (H/R) injury. In the present study, effects of salvianolic acid A (1) on heart H/R injury through its antioxidant activity were examined, using a molecule-based ROS scavenging system and cardiomyocyte model of H/R injury, as well as isolated rat heart model. As a result, 1 showed a potent antioxidant activity, scavenging all of the tested ROS and DPPH (2,2-diphenyl-1-picrylhydrazyl). The antioxidant effect of 1 was also observed in cardiomyocytes exposed to H/R. Compound 1 remarkably decreased dihydroethidium and dichlorofluorescein fluorescence and increased cell viability and mitochondrial membrane potential, ΔΨ(m), when compared to the H/R group. In isolated rat hearts exposed to H/R, 1 markedly increased the coronary flow, the peak of pressure development and the valley of pressure development, and significantly reduced the left ventricular end diastolic pressure when compared to the H/R group. These results suggested that 1 had significant protective effects against H/R-induced myocardial injury through its antioxidant activity.

Topics: Animals; Biphenyl Compounds; Caffeic Acids; Cardiotonic Agents; Disease Models, Animal; Heart; Hypoxia; Lactates; Molecular Structure; Myocytes, Cardiac; Oxidative Stress; Picrates; Rats; Reactive Oxygen Species