Genistein mitigates oxidative stress and inflammation by regulating Nrf2/HO-1 and NF-κB signaling pathways in hypoxic-ischemic brain damage in neonatal mice
Yuan Li, Jinjia Zhang, Ru-Jia Chen, Ling Chen, Su Chen, Xiaofei Yang, Jia‐Wei Min
Abstract
Background: Oxidative stress and neuroinflammation play crucial roles in the progression of neonatal hypoxic-ischemic brain damage (HIBD). Genistein, a natural phytoestrogen, has been found to protect against ischemic brain injury. However, its effects and potential mechanisms in HIBD have not yet been explored. Methods: . Results: Our results showed that genistein treatment effectively reduced cerebral infarction, attenuated neuronal injury and apoptosis, and contributed to the long-term recovery of neurological outcomes and brain atrophy in neonatal HIBD mice. Moreover, genistein ameliorated HIBD-induced oxidative stress and neuroinflammation. Meanwhile, genistein significantly increased cell viability, reversed neuronal injury and decreased cell apoptosis after OGD/R injury. Finally, the activation of the Nrf2/HO-1 pathway and inhibition of the NF-κB pathway by genistein were verified in the brain tissues of neonatal mice subjected to HIBD and in primary cortical neurons exposed to OGD/R. Conclusions: Genistein exerted neuroprotective effects on HIBD by attenuating oxidative stress and neuroinflammation through the Nrf2/HO-1 and NF-κB signalling pathways.