Puerarin esters mitigate oxygen and glucose deprivation-reoxygenation-induced injury in microglial cells

Abstract Puerarin esters (PAES) are novel isoflavone derivatives of puerarin. 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 apoptosis-related signaling pathways. To clarify the protective role of PAES in ischemic stroke, the 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 cell viability and promoted microglial polarization toward the anti-inflammatory M2 phenotype under OGD conditions. Furthermore, PAES decreased OGD/R-induced cell death via suppressing cleaved-caspase 3 expression and decreasing the Bax/Bcl-2 ratio. PAES treatment up-regulated SOD1 and Nrf2 expression, P-Akt, while P-JNK, P-P38, NF-κB expressions were significantly down-regulated. In conclusion, this study reports that PAES effectively mitigates OGD/R-caused inflammatory damage and oxidative stress in microglia cells, thereby suggesting a potential therapeutic approach for ischemic stroke. Graphical Abstract