RESUMO
BACKGROUND: Vascular endothelial cell injury is not only the initiating factor of cardiovascular and cerebrovascular diseases but also the essence of blood stasis. Levistilide A (LA), a natural component isolated from the traditional Chinese herb, Ligusticum chuanxiong Hort, has traditional effects on improving blood circulation and removing stasis. In this study, the effects and potential mechanisms of LA in the rat model of blood stasis and the mechanism in endothelial cell injury have been explored. MATERIALS AND METHODS: In this experiment, the effects of LA on the model of acute blood stasis in rats were explored. The blood samples were collected for the measurement of coagulation and hemorheological indices, and the carotid arteries were also excised from rats for hematoxylin-eosin (HE) staining and immunohistochemistry (IHC). In addition, the improvement effects of LA on the H2O2-induced human umbilical vein endothelial cell (HUVEC) injury model were evaluated. And the cell viability detection was conducted by the CCK8 assay, and the pathway-related protein expressions were detected by western blotting. RESULTS: In vivo, compared with the model group, the treatment of LA (10 mg/kg) could reduce the FIB (fibrinogen) content (P < 0.01), increase the INR (international normalized ratio) and PT (prothrombin time) (P < 0.01), and reduce the plasma viscosity (P < 0.05) and whole blood viscosities of low, medium, and high shear rates in the blood of blood stasis model rats (P < 0.01). In vitro, the cell viability in the LA-pretreated group was higher than that of the model group (P < 0.05). The expression levels of PI3K, AKT, and eNOs in the LA-pretreated group were increased (P < 0.01) as compared to the model group. CONCLUSION: These findings demonstrated that LA has the ability to improve blood hypercoagulation and blood viscosity, and enhance the viability of cells. It is more likely that it exerts a protective effect on the endothelial cell through the PI3K-AKT-eNOs pathway. These results indicate LA will be a potential candidate to cure blood stasis with endothelial cell injury.
RESUMO
Memory loss is a complication of diabetes which requires new approaches to its treatment. Shengmai San (SMS) is a famous traditional Chinese formula containing Panax ginseng, Ophiopogon japonicas, and Schisandra chinensis, whereas Radix puerariae has many reported pharmacological uses. In this study the combination, as Jiawei SMS (J-SMS) was screened for its ability to reverse diabetes-associated cognitive decline in rats. This was assessed behaviorally in diabetic rats (Streptozotocin, 45 mg/kg), with biochemical and western blot analysis (Akt and CREB). Diabetic rats showed fasting blood glucose (FBG) in the range of 13-15 mM throughout the study. J-SMS (0.5, 1.5, 4.5 g/kg) treatment significantly improved learning and memory deficit among diabetic rats as evidenced by preference for novel object, reduced escape latency and increased number of platform crossings (p < .05) in the NORT and MWM tests. Treatment with J-SMS also significantly improved the histopathological changes in the diabetic brain and increased the protein expression of AKT and CREB, required for proper memory function (p < .01). This study highlighted that J-SMS can reverse reference and working memory deficit among diabetic rats by modulating AKT and CREB proteins activation. Thus, J-SMS formulation might be possible candidate for further development.
