Isoliquiritigenin protects against blood‑brain barrier damage and inhibits the secretion of pro-inflammatory cytokines in mice after traumatic brain injury.

Traumatic brain injury (TBI) caused by an external mechanical force acting on the brain is a serious neurological condition. Inflammation plays an important role in prolonging secondary tissue injury after TBI, leading to neuronal cell death and dysfunction. Isoliquiritigenin (ILG) is a flavonoid monomer with anti-inflammatory characteristic. Thus, we had investigated the potential protective effects of ILG on TBI-induced injuries and identified the mechanisms underlying it. Here, we have demonstrated that ILG preserves blood brain barrier (BBB) integrity in vivo, suppresses the activation of microglia and inflammatory responses in mice after TBI, consequently leading to neurofunctional deficits, brain oedema, structural damage, and macrophage infiltration. In vitro, ILG exerts anti-inflammatory effect, and upregulates tight junction proteins 120‑β‑catenin and occludin in SH‑SY5Y cells under oxygen glucose deprivation/reoxygenation (OGD/D) condition. Additionally, we found that PI3K/AKT/GSK‑3β signalling pathway is involved in ILG treatment for TBI. To further confirm it, we had used SC79 (ethyl 2‑amino‑6‑chloro‑4‑(1‑cyano‑2‑ethoxy‑2‑oxoethyl)‑4H‑chromene‑3‑carboxylate), an Akt specific activator, to activate Akt, we found that SC79 partially reduces the protective effect of ILG for TBI. Overall, our current study reveals the neuroprotective role of ILG on TBI-induced BBB damage, downregulated tight junction proteins via PI3K/AKT/GSK‑3β signalling pathway. Furthermore, ILG suppresses the secretion of pro-inflammatory cytokines after TBI through inhibiting the PI3K/AKT/GSK‑3β/NF‑κB signalling pathway. Our findings suggest that GSK‑3β is a key regulatory factor during TBI-induced secretion of inflammatory cytokines, neuronal apoptosis and destruction of BBB.