Cryptotanshinone Attenuates Oxygen-Glucose Deprivation/ Recovery-Induced Injury in an in vitro Model of Neurovascular Unit

Cryptotanshinone (CTs), an active component isolated from the root of Salvia miltiorrhiza, has been demonstrated to be effective for both myocardial and hepatic ischemia/reperfusion damage. We here established an oxygen-glucose deprivation/recovery (OGD/R) model of Neurovascular Unit (NVU) in vitro to observe the effects of CTs on cerebral ischemia/reperfusion injury (CIRI), and explore the underlying mechanisms. CTs was observed to significantly inhibit the OGD/R-induced neuronal apoptosis, and reduce the activation of Caspase-3 and poly (ADP-ribose) polymerase (PARP), as well as the increase of Bax/Bcl-2 ratio in neurons under OGD/R condition. The inhibitory effects of CTs on neuron apoptosis were associated with the blocking of the JNK and p38 MAPK signaling pathway. CTs also remarkably ameliorated OGD/R-induced reduction of transepithelial membrane resistance (TEER) values and the increase of transendothelial permeability coefficient (Pe) of sodium fluorescein (SF) by enhancing the expression of ZO-1, Occludin and Claudin-5 in BMECs, which might be related to the downregulation of matrix metalloprotein (MMP)-9 expression. Altogether, our data indicate that CTs has protective effects against OGD/R injure in NVU models in vitro via the amelioration of neuronal apoptosis and BBB disrupt, suggesting that CTs is a candidate medicine for CIRI.