Pinocembrin protects the neurovascular unit by reducing inflammation and extracellular proteolysis in MCAO rats.

The purpose of the present study was to examine the protective action and mechanisms of pinocembrin (1) on the neurovascular unit (NVU) in permanent cerebral ischemic rats. Focal cerebral ischemia was induced by occlusion of middle cerebral artery (MCAO) in rats. Compound 1 (3, 10, or 30 mg/kg) was intravenously injected at 0, 8, 16 h after MCAO. At 24 h of occlusion, 1 alleviated neuronal apoptosis, edema of astrocytic end-feet, and the deformation of endothelial cells and capillaries as revealed by the transmission electron microscopy study. To understand the mechanisms of action, the anti-inflammation effect of 1 was examined. Compound 1 reduced the expressions of tumor necrosis factor-alpha, interleukin-1beta, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, inducible NO synthase and aquaporin-4; inhibited the activation of microglias and astrocytes; and downregulated the expression of matrix metalloproteinases (MMPs) in the ischemic brain. The ischemia-induced decreases in mRNA expressions of tight junction constituent proteins, occludin and ZO-1, were also inhibited by 1. These results indicated that 1 can protect the rat brain against ischemia injury by inhibiting the inflammatory cascade, reducing the expression of MMP-9, and preventing the integrity of tight junction. This resulted in the protective action of 1 on the NVU.

Protective effects of salidroside on endothelial cell apoptosis induced by cobalt chloride.

Salidroside is a major constituent of Rhodiola rosea L. that elicits beneficial effects for ischemic cardiovascular diseases. The aim of this study was to investigate the protective effects of salidroside on endothelial cells apoptosis induced by the hypoxia mimicking agent, cobalt chloride. After challenge with cobalt chloride for 24 h, loss of cell viability and excessive apoptotic cell death were observed in EA.hy926 endothelial cells, and the level of intracellular reactive oxygen species (ROS) increased concentration-dependently. However, the endothelial cell apoptosis and excessive ROS generation were attenuated markedly by salidroside pretreatment. In addition, salidroside inhibited activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase (PARP) induced by cobalt chloride, decreased expression of Bax and rescued the balance of pro- and anti-apoptotic proteins. These findings suggest that salidroside protects endothelial cells from cobalt chloride-induced apoptosis as an antioxidant and by regulating Bcl-2 family. Salidroside may represent a novel therapeutic agent for the treatment and prevention of hypoxia and oxidative stress-related diseases.