LAUSR

Salidroside, an active component of Rhodiola rosea , reduces inflammation and neuronal damage after middle cerebral artery occlusion (MCAO) with reperfusion, partly by inhibiting cerebral complement C3 activation. However, the mechanisms of this inhibition are not fully understood. In this study, we investigated which cerebral cells might contribute to the inhibition of complement by salidroside and the consequences of this inhibition. We used human umbilical endothelial cells (HUVEC) as a model of cerebral endothelium and found that salidroside prevented the increases of C3 and its active fragment C3a, and the associated increases in C1q and C2, otherwise caused by oxygen-glucose deprivation followed by restoration (OGD/R). However, salidroside did not affect C1q, C2 or C3 in astrocytes and microglial BV2 cells after OGD/R. Salidroside also prevented the decreases in CD46 and CD59, and the increases in VCAM-1, ICAM-1, P-selectin and E-selectin caused by OGD/R in HUVEC, which were associated with decreasing LDH release and increasing Bcl-2/Bax ratio. None of these effects of salidroside occurred in the absence of oxygen-glucose restoration. Moreover, salidroside and C3a receptor antagonist reduced the markers of endothelial activation and neutrophil adhesion to HUVEC after OGD/R to similar extents, and their effects were not additive. Correspondingly, salidroside reduced the markers of endothelial activation and neutrophilic infiltration in the rat brains after MCAO with reperfusion. These results suggest endothelium is an important locus of inhibition of complement by salidroside, restoring an anti-inflammatory endothelial phenotype after oxidative stress, partly by inhibiting classical complement activation and partly by increasing CD46 and CD59, in association with anti-apoptotic effects. These endothelial effects may contribute to the protection afforded by salidroside in cerebral ischemia-reperfusion injury.