Molecular Mechanism of Compound Glycyrrhizin in Kainic Acid-Induced Epilepsy in Rat Model.

This study explores the effects of compound glycyrrhizin (GL) on seizures in the rat model and its potential molecular mechanisms. Eighty male, healthy, and clean-graded Sprague Dawley (SD) rats, aged 1 month, were used in this study. Of these, 60 rats were selected to construct the epilepsy model and were randomly divided into the GL group (status epilepticus (SE) + GL, n = 60) and the model group (Model, n = 10), and received tail vein injections of GL or saline, respectively. Another ten normal rats served as the control group (Control). According to different doses of GL, they were divided into the high dose group (HGL, 50 mg/kg, n = 20), the medium dose group (MGL, 20 mg/kg, n = 20), and the low dose group (LGL, 10 mg/kg, n = 20). The expression levels of high mobility group box 1 (HMGB1) and Toll-like receptor-4 (TLR-4) in serum and hippocampal tissue of rats 24 h after SE were detected by enzyme-linked immunosorbent assay (ELISA) and Western blot. The neuronal density in brain tissue and the number of NeuN-positive cells in the cornu ammonis 1 (CA1) and cornu ammonis 3 (CA3) areas of rats in each group were statistically compared. SE incidence rate in the Model group was 40%, and the survival rate was 60%. The grade III seizure onset time (SOT) after kainic acid (KA) injection was (22.19 ± 2.07) min. The SOT in the SE + GL group after KA injection was (35.76 ± 3.46) min; the SE incidence rate was 10%; the survival rate was 90%. The relative expression of TLR-4 mRNA in the hippocampal tissue at different time points (3 h, 12 h, and 24 h) was markedly higher than that in the Control group, showing significance (P < 0.05). The expression levels of HMGB1 and TLR-4 in the hippocampal tissue of rats in the Model group were markedly higher than in other groups, and compared with the Model group, the expression levels of HMGB1 and TLR-4 in the hippocampal tissue of the HGL, MGL, and LGL groups were markedly reduced (P < 0.05). The neuronal density in the cerebral cortex of rats in the GL group was markedly reduced compared to the Model (P < 0.05), and the normal neuronal density in the cerebral cortex of the HGL, MGL, and LGL groups was markedly lower than that in the Control group (P < 0.05). The normal neuronal density in the cerebral cortex of the HGL and MGL groups was markedly increased compared to the Model group (P < 0.05). The number of NeuN-positive cells in the CA1 and CA3 areas of rats in the Model and SE + GL groups was greatly reduced, and the number of NeuN-positive cells in the CA1 area was markedly higher than that in the CA3 area in the HGL group and the Model group (P < 0.05). The compound GL was found to delay the onset of the first seizure in rats, reduce seizure sensitivity, and alleviate symptoms. GL treatment effectively decreased the expression of HMGB1 and TLR-4, reduced the pathological damage associated with epilepsy, and contributed to the protection of neurons.