Salvianolic acid A attenuates cerebral ischemia/reperfusion injury induced rat brain damage, inflammation and apoptosis by regulating miR-499a/DDK1.

Background And Objectives: Salvianolic acid A (SAA) is a main component derived from Salvia miltiorrhiza and has been revealed to protect against cerebral ischemia/reperfusion injury (CIRI). The present study was designed to evaluate the neuroprotective role of SAA in CIRI and explore its underlying mechanism and .

Methods: To determine the neuroprotective effects of SAA on CIRI , the middle cerebral artery occlusion (MCAO) rat model was established. Besides, oxygen-glucose deprivation/reperfusion (OGD/R)-induced PC12 cells were used to analysis the effects of SAA on CIRI . Neurological deficit score, brain water content, cell proliferation, apoptosis and inflammation were measured. In addition, the effects of SAA on miR-449a/DKK1 and Wnt/β-catenin pathway were evaluated.

Results: The level of miR-449a was decreased in MCAO rat models as well as OGD/R-induced PC-12 cells. SAA could significantly inhibit cell apoptosis and inflammation both in MCAO rat model and OGD/R-induced PC-12 cells. Also, SAA inhibited cerebral edema and promoted PC12 cell proliferation. Besides, we proved that the 3'-UTR of DKK1 mRNA is the target of miR-449a. Furthermore, we demonstrated that SAA could activate Wnt/β-catenin pathway and play the neuroprotective role by regulating miR-499a/DDK1.

Conclusion: Taken together, these results suggest that SAA could increase miR-449a level and then inhibit DDK1 expression to activate Wnt/β-catenin pathway, leading to the alleviation of cerebral ischemia/reperfusion injury and .