Effects of Chaihu longgu muli decoction on neuronal damage in refractory epilepsy rats and its mechanism
- VernacularTitle:柴胡加龙骨牡蛎汤对难治性癫痫大鼠神经元损伤的影响及机制
- Author:
Ping SHAN
1
;
Jilong ZHANG
2
Author Information
1. Dept. of Neurology,Wuhan First Hospital,Wuhan 430022,China
2. Emergency Department,Wuhan First Hospital,Wuhan 430022,China
- Publication Type:Journal Article
- Keywords:
refractory epilepsy;
Chaihu longgu muli decoction;
neuronal damage;
COX-2/PGE2 signaling pathway
- From:
China Pharmacy
2025;36(6):692-697
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To explore the effect and potential mechanism of Chaihu longgu muli decoction on hippocampal neuronal damage in refractory epilepsy rats. METHODS The refractory epilepsy rat model was established by intracerebroventricular injection of kainic acid. The refractory epilepsy rats were randomly assigned into model group, celecoxib group (positive control), Chaihu longgu muli decoction group, Chaihu longgu muli decoction+empty loading group, Chaihu longgu muli decoction+cyclooxygenase-2 (COX-2) overexpression group, with 12 rats in each group. Another 12 rats were selected as sham operation group (injected with normal saline into the lateral ventricle). After 8 weeks of corresponding drug/normal saline intervention, Racine grading criteria were applied to evaluate the seizure behavior of rats; pathological changes and cell apoptosis in CA3 region of hippocampal tissue were observed; ELISA method was adopted to detect the levels of COX-2, prostaglandin E2 (PGE2), and tumor necrosis factor-α (TNF-α) in hippocampal tissue. The colorimetric method was applied to detect the content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in hippocampal tissue. Real-time fluorescence quantitative PCR and Western blot were applied to detect the mRNA and protein expressions of COX-2 and P-glycoprotein (P-gp) in hippocampal tissue. RESULTS The rats in the sham operation group had no epileptic seizures. Compared with sham operation group, Racine grade of epilepsy, apoptotic rate of hippocampal tissue cells, COX-2, PGE2 and TNF-α levels, MDA contents, mRNA and protein levels of COX-2 and P-gp in the model group increased significantly, while SOD activity decreased significantly (P<0.05); prominent damage was observed in the hippocampal CA3 region. Compared with model group, Racine grade of epilepsy, apoptotic rate of hippocampal tissue cells, COX-2, PGE2 and TNF-α levels, MDA contents, mRNA and protein levels of COX-2 and P-gp in celecoxib group and Chaihu longgu muli decoction group decreased significantly, while SOD activity increased significantly(P<0.05); the neuronal damage in hippocampal CA3 region was alleviated. Compared with Chaihu longgu muli decoction group and Chaihu longgu muli decoction+ empty loading group, the improvement in the aforementioned indicators in rats from Chaihu longgu muli decoction+COX-2 overexpression group was significantly reversed (P<0.05), with exacerbated neuronal damage in the CA3 region of the hippocampal tissue. CONCLUSIONS Chaihu longgu muli decoction may alleviate hippocampal neuronal damage in refractory epilepsy rats by inhibiting the activation of COX-2/PGE2 signaling pathway, inhibiting inflammation and oxidative stress, thereby alleviating hippocampal neuronal damage in refractory epilepsy rats.