Pratensein Mitigates Oxidative Stress and NLRP3 Inflammasome Activation in OGD/R-Injured HT22 Cells by Activating Nrf2-Anti-oxidant Signaling

The current investigation seeks to uncover the neuroprotective effects and mechanisms of pratensein (Pra) against cerebral ischemia-reperfusion (CI/R) injury. An in vitro model was created by subjecting HT22 cells to oxygen-glucose deprivation/reoxygenation (OGD/R) injury. Various doses of Pra were administered to HT22 cells during the process of OGD/R. Nrf2 knockdown was achieved by siRNA transfection. Pra antagonized OGD/R-triggered HT22 cell damage, as suggested by increased cell viability and reduced levels of LDH secretion. Additionally, Pra reversed OGD/R-induced cell apoptosis, oxidative stress, and inflammatory injury. Transfection of Nrf2 siRNA partially ameliorated the protective effects of Pra on the OGD/R-stimulated increase in cell apoptosis, oxidative stress, and inflammatory response in HT22 cells. Pra significantly inhibited the expression of nod-like-receptor-protein-3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, and cleaved caspase-1 protein in OGD/R-induced cells. Nrf2 knockdown reversed the benefits of Pra on NLRP3 inflammasome activation. Besides, Pra administration mitigated middle cerebral artery occlusion/reperfusion-induced cerebral infarction, neurological deficits, and neuronal apoptosis in vivo. This study found that Pra suppresses NLRP3 inflammasome activation through Nrf2 activation, resulting in reduced inflammatory responses and rates of apoptosis in OGD/R-stimulated HT22 cells, highlighting the neuroprotective properties of Pra in CI/R.

Automated summary

This study demonstrates the neuroprotective effects of Pra against cerebral ischemia-reperfusion injury. Pra suppresses NLRP3 inflammasome activation through Nrf2 activation, resulting in reduced inflammatory responses and rates of apoptosis.