Chrysin, which targets PLAU, protects PC12 cells from OGD/R-stimulated damage through repressing the NF-κB signaling pathway

Cerebral ischemia reperfusion injury (CIRI) is a great challenge for the patients with brain ischemia, but its pathophysiological mechanism has not been clearly explored. This study aims to decipher the effect of chrysin and plasminogen activator urokinase (PLAU) in CIRI. The immune-related genes were collected from the ImmPort website, and the differentially expressed genes were determined based on the Gene Expression Omnibus (GEO) database. PC12 cells were used to establish an ischemic stroke model under the condition of oxygen-glucose deprivation and reoxygenation (OGD/R). Small interfering RNA strategy was employed to knock down the PLAU expression of PC12 cells. The proliferation and apoptosis rates of PC12 cells treated by OGD/R or/and chrysin were detected with Cell Counting Kit 8 (CCK-8) and flow cytometry. The protein and mRNA expressions were measured using western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR). PLAU was identified as a candidate for CIRI treatment and expressed at higher levels in CIRI tissues compared with that in normal controls. Chrysin was determined as a crucial agent that could decrease the expression of PLAU. Chrysin significantly promoted the cell proliferation, inhibited the protein levels of PLAU, p–NF–κB, and p-IKκB in PC12 cells after OGD/R. Silencing of PLAU strengthened the protective effect of chrysin on PC12 cells treated by OGD/R, including the improvement of cell viability and suppression of apoptosis. Chrysin inactivated the NF-κB pathway via targeting PLAU in OGD/R-stimulated PC12 cells. Chrysin prevented PC12 cells from OGD/R-stimulated damage via decreasing PLAU expression and inactivating the NF-κB signaling pathway.