Protective effect of puerarin esters against oxygen and glucose deprivation-reoxygenation- induced microglial cells damage

Abstract

Abstract Puerarin esters (PAES) modified by puerarin (PU) are a novel isoflavone. Network pharmacology analysis revealed that PAES with medium-long chain lengths may exert a neuroprotective effect against ischemic stroke through NF-κB signaling, TNF signaling, and other apoptosis-related signaling pathways. To clarify the protective effect of PAES on ischemic stroke, this present study was carried out by using a typical cell model-oxygen and glucose deprivation-reoxygenation (OGD/R)-induced microglial cells model. Results showed that pretreatment with PAES (25 µM) remarkably increased oxygen and glucose deprivation (OGD)-induced cell viability and promoted the polarization of these cells to the M2 phenotype. In addition, PAES (25 µM) decreased OGD/R-induced cell death via suppressing cleaved-caspase 3 expression and decreasing the Bax/Bcl-2 ratio. We further demonstrated that PAES, by activating the Nrf2/Akt pathway, up-regulated SOD1 expression and inhibited the oxidative stress response. A further analysis revealed that PAES significantly decreased OGD/R-induced TNF-α and IL-1β levels and downregulated MMP2 and MMP9 expression, which was related with NF-κB translocation and P38-JNK signaling pathway. In conclusion, this study reports that PAES effectively antagonize OGD/R-caused inflammation damage and oxidative stress in microglia cells, thereby offering a new direction for ischemic stroke-induced cell damage.