Glycyrrhizin, an HMGB1 inhibitor, exhibits neuroprotective effects in rats after lithium-pilocarpine-induced status epilepticus

Abstract Objectives It has been proven that extracellular HMGB1 is involved in progression of neurologic disorders, such as stroke, traumatic brain injury, meningitis and epilepsy. Glycyrrhizin (GL) is a direct inhibitor of HMGB1, and blocks HMGB1 release into the extracellular. We aim in this study to investigate the neuroprotective effects of GL in a rat model after lithium-pilocarpine-induced status epilepticus (SE). Methods Adult male SD rats were divided into three groups: Sham group, SE-group and (SE + GL)-treated group. The HMGB1 expression in serum and hippocampus, the damage extent of blood brain barrier (BBB) and hippocampal neuronal damage were evaluated by enzyme-linked immunosorbent assay, immunohistochemistry, western blot and nissl's staining. Key findings Glycyrrhizin markedly reduced HMGB1 expression in serum and hippocampus, prevented HMGB1 translocation from nucleus to cytoplasm in hippocampal CA1, CA3 and hilus areas of SE rats. Meanwhile, GL significantly ameliorated neuronal damage in the CA1, CA3 and hilus areas of hippocampus, and protected BBB disruption after SE. The administration of GL significantly decreased the mortality from 25 to 8.9% in rats. Conclusions Glycyrrhizin may exert neuroprotective effects via inhibiting HMGB1 and protect BBB permeability in lithium-pilocarpine-induced rats with SE.