Neuroprotective effect of licochalcone A against oxygen‐glucose deprivation/reperfusion in rat primary cortical neurons by attenuating oxidative stress injury and inflammatory response via the SIRT1/Nrf2 pathway

Abstract Perinatal hypoxic‐ischemic encephalopathy (HIE) is a leading cause of neonatal death and neurological disability. Oxidative stress and neuroinflammation are typical pathogenic factors of HIE. Licochalcone A (LCA) exerts various biological properties, including anti‐inflammatory and antioxidant activities. However, no data have been reported to elucidate the role of LCA in the development of HIE. In the present study, primary cultured rat cortical neurons were exposed to oxygen‐glucose deprivation/reoxygenation (OGD/R) in vitro to simulate the in vivo situation of neonatal HIE. Interestingly, LCA significantly antagonized cell injury under OGD/R by increasing cell survival, inhibiting lactate dehydrogenase (LDH) release and cell apoptosis. Furthermore, treatment with LCA suppressed oxidative stress by decreasing reactive oxygen species (ROS) production and malondialdehyde (MDA) content, and increasing superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in primary rat cortical neurons after OGD/R. LCA stimulation also restrained OGD/R‐triggered increase in pro‐inflammatory cytokines tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) production. Importantly, LCA treatment effectively counteracts OGD/R‐mediated downregulation of silent information regulator 1 (SIRT1), nuclear factor erythroid2‐related factor 2 (Nrf2), and heme oxygenase‐1 (HO‐1), and upregulation of nuclear factor kappa B p65 (NF‐κB p65). Moreover, administration with SIRT1 inhibitor EX527 partly abolished LCA‐induced neuroprotective effects on rat cortical neurons exposed to OGD/R. In conclusion, our study indicates that LCA exerts a neuroprotective effect against OGD/R‐induced neuronal injury in rat primary cortical neurons, suggesting that LCA might act as a candidate therapeutic target drug used for HIE and related diseases.