Effect of glycyrrhizin acid on the seizure onset and hippocampal neuron injury in kainic acid induced epileptic rat models

Abstract

Objective To explore the effect and the possible mechanism of glycyrrhizin acid (GA) on the seizure onset and hippocampal neuron injury in kainic acid (KA) induced epileptic rat models. Methods The epilepsy model was established by injecting KA into the rat hippocampus. Rats were randomly divided into sham group, epilepsy group (EP group), and GA group (25 mg/kg group and 50 mg/kg group). After injection, the latency period and severity of seizure of rats in each group were observed. The acute phase EEG of rats in different groups were monitored. The neuron injury in hippocampus CA3 region and the expression of high⁃mobility group box 1 (HMGB1) of rats in different groups were detected by immunohistochemistry staining and Western blotting. Results Compared to the EP group, the epileptic seizure latency of GA 25 mg/kg group and 50 mg/kg group significantly lengthened [(109.33 ± 42.84) min vs. (51.17 ± 22.31) min, t = ⁃ 2.950, P = 0.015; (109.50 ± 35.79) min vs. (51.17 ± 22.31) min, t = ⁃ 3.388, P = 0.007], the times of seizure ≥ Ⅳ grade during 6 h after injection in GA 25 mg/kg group and 50 mg/kg group significantly reduced [(2.83 ± 0.75) times vs. (5.00 ± 1.55) times, t = 3.081, P = 0.012; (2.67 ± 1.75) times vs. (5.00 ± 1.55) times, t = 2.445, P = 0.035]. After the treatment of GA, the number of spike and sharp waves in the acute phase EEG obviously decreased. In the acute stage of epileptic seizure, the neurons number in hippocampus CA3 region of EP group reduced, and was significantly less than that of sham group [(40.33 ± 5.69) neurons vs. (72.33 ± 7.51) neurons, t = 5.886, P = 0.004]; while the number of neurons in hippocampus CA3 region of GA 25 mg/kg group and 50 mg/kg group increased, and was significantly more than that of EP group [(58.33 ± 2.52) neurons vs. (40.33 ± 5.69) neurons, t = ⁃ 5.014, P = 0.007; (57.00 ± 6.25) neurons vs. (40.33 ± 5.69) neurons, t = ⁃ 3.418, P = 0.027]. The expression of HMGB1 [integrated optical density (IOD)] in hippocampus CA3 region of EP group heightened, and was significantly higher than that of sham group [(3.79 ± 0.50) × 106 IOD vs. (2.16 ± 0.45) × 106 IOD, t = ⁃ 4.216, P = 0.014]; while the expression of HMGB1 in hippocampus CA3 region of GA 25 mg/kg group and 50 mg/kg group decreased, and was significantly lower than that of EP group [(2.50 ± 0.52) × 106 IOD vs. (3.79 ± 0.50) × 106 IOD, t = 3.090, P = 0.037; (2.66 ± 0.44) × 106 IOD vs. (3.79 ± 0.50) × 106 IOD, t = 2.955, P = 0.042]. The expression of HMGB1 protein (relative gray value) in hippocampus tissue detected of EP group increased, and was significantly higher than that of sham group (1.19 ± 0.17 vs. 0.54 ± 0.14, t = ⁃ 5.078, P = 0.007); while the expression of HMGB1 protein in hippocampus tissue of GA 25 mg/kg group and 50 mg/kg group lessened, and was significantly lower than that of EP group (0.65 ± 0.04 vs. 1.19 ± 0.17, t = 5.286, P = 0.028; 0.58 ± 0.13 vs. 1.19 ± 0.17, t = 4.953, P = 0.008). Conclusions GA can prolong the epileptic seizure latency, reduce the seizure severity and epileptic discharges, and alleviate the hippocampal neuron injury in KA induced epileptic rats. These effects may be associated with its inhibition on the expression of HMGB1.

doi：10.3969/j.issn.1672⁃6731.2025.04.007