Search

Stroke is an acute cerebrovascular disease caused by ruptured or blocked blood vessels. For the prevention of ischemic stroke, the coagulation state of blood and cerebrovascular protection should be considered. Our previous study has shown that salvianolic acid A (SAA), which is a water-soluble component from the root of Salvia Miltiorrhiza Bge, prevents thrombosis with a mild inhibitory effect on platelet aggregation. In this study we investigated the preventive effects of SAA on cerebrovascular endothelial injury caused by ischemia in vivo and oxygen-glucose deprivation (OGD) in vitro, and explored the underlying mechanisms. An autologous thrombus stroke model was established in SD rats by electrocoagulation. SAA (10 mg/kg) was orally administered twice a day for 5 days before the operation. The rats were sacrificed at 24 h after the operation. We showed that pretreatment with SAA significantly improved the neurological deficits, intracerebral hemorrhage, BBB disruption, and vascular endothelial dysfunction as compared with model group. In human brain microvascular endothelial cells (HBMECs), pretreatment with SAA (10 μM) significantly inhibited OGD-induced cell viability reduction and degradation of tight junction proteins (ZO-1, occludin, claudin-5). Furthermore, we found that SAA inhibited the upregulation of Src signaling pathway in vivo and vitro and reversed the increased expression of matrix metalloproteinases (MMPs) after ischemic stroke. In conclusion, our results suggest that SAA protects cerebrovascular endothelial cells against ischemia and OGD injury via suppressing Src signaling pathway. These findings show that pretreatment with SAA is a potential therapeutic strategy for the prevention of ischemic stroke.

Salvianolic acid A (SalA) is one of the main active ingredients of Salvia miltiorrhizae. The objective of this study was to evaluate the effect of SalA on the diabetic vascular endothelial dysfunction (VED). The rats were given a high-fat and high-sucrose diet for 1 month followed by intraperitoneal injection of streptozotocin (30 mg/kg). The diabetic rats were treated with SalA (1 mg/kg, 90% purity) orally for 10 weeks after modeling, and were given a high-fat diet. Contractile and relaxant responses of aorta rings as well as the serum indications were measured. Our results indicated that SalA treatment decreased the level of serum Von Willebrand factor and ameliorated acetylcholine-induced relaxation and KCl-induced contraction in aorta rings of the diabetic rats. SalA treatment also reduced the serum malondialdehyde, the content of aortic advanced glycation end products (AGEs), and the nitric oxide synthase (NOS) activity as well as the expression of endothelial NOS protein in the rat aorta. Exposure of EA.hy926 cells to AGEs decreased the cell viability and changed the cell morphology, whereas SalA had protective effect on AGEs-induced cellular vitality. Our data suggested that SalA could protect against vascular VED in diabetes, which might attribute to its suppressive effect on oxidative stress and AGEs-induced endothelial dysfunction.

Aims: The present study aims to evaluate the beneficial effect of salvianolic acid A (SAA) on the alterations in vascular reactivity of streptozotocin (STZ)-induced diabetic rats., Main Methods: Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg). Following 16 weeks of SAA treatment (1 mg/kg/day), thoracic aortic rings of rats were mounted in organ baths. Contractile responses to noradrenaline (NA) and KCl and relaxant responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were assessed., Key Findings: Loss of weight, hyperglycemia, elevated content of malondialdehyde (MDA) and decline of total antioxidant capacity (TAC) were observed in diabetic rats. SAA could reverse these metabolic and biochemical abnormalities. Compared to the control, the maximum contraction (E(max)) to NA, but not sensitivity (pD(2)), increased significantly in diabetic aortas, which was prevented by SAA treatment. However, the response of rat aortas to KCl (E(max) and pD(2)) was not altered either in diabetic group or SAA treatment compared with that of normal control group. We also observed the significant decrease in relaxation to ACh rather than SNP in diabetic group compared with controls, and SAA treatment could revert the ACh response., Significance: It is concluded that oral administration of SAA can significantly improve glucose metabolism and inhibit oxidative injury as well as protect against impaired vascular responsiveness in STZ-induced diabetic rats.

The present study was designed to evaluate the cardioprotective potential of salvianolic acid A on isoproterenol-induced myocardial infarction in rats. Hemodynamic parameters and lead II electrocardiograph were monitored and recorded continuously. Cardiac marker enzymes and antioxidative parameters in serum and heart tissues were measured. Assay for mitochondrial respiratory function and histopathological examination of heart tissues were performed. Isoproterenol-treated rats showed significant increases in the levels of lactate dehydrogenase, aspartate transaminase, creatine kinase and malondialdehyde and significant decreases in the activities of superoxide dismutase, catalase and glutathione peroxidase in serum and heart. These rats also showed declines in left ventricular systolic pressure, maximum and minimum rate of developed left ventricular pressure, and elevation of left ventricular end-diastolic pressure and ST-segment. In addition, mitochondrial respiratory dysfunction characterized by decreased respiratory control ratio and ADP/O was observed in isoproterenol-treated rats. Administration of salvianolic acid A for a period of 8 days significantly attenuated isoproterenol-induced cardiac dysfunction and myocardial injury and improved mitochondrial respiratory function. The protective role of salvianolic acid A against isoproterenol-induced myocardial damage was further confirmed by histopathological examination. The results of our study suggest that salvianolic acid A possessing antioxidant activity has a significant protective effect against isoproterenol-induced myocardial infarction.