Objective:To explore regulatory effect of oridonin(Ori)-mediated NLRP3 inflammasome on seizure susceptibility in PTZ-induced chronic epileptic mice.Methods:Chronic epilepsy was induced in mice using pentylenetetrazol(PTZ),and the mice were treated with different doses of Ori.Behavioral changes(seizure severity,latency,and frequency)were observed before and after treat-ment.Hippocampal tissues were examined using HE staining,and the expression levels of NLRP3 and related proteins were detected by Western blot.Results:Behavioral results showed that Ori treatment prolonged seizure latency,reduced seizure severity,and decreased the frequency of spontaneous seizures,particularly in the medium-and high-dose groups.HE staining and Western blot results were con-sistent with the behavioral findings.Ori treatment alleviated epilepsy-induced pathological damage,reduced inflammatory infiltration,and downregulated the expression levels of NLRP3 and related proteins in the brain.Conclusion:Ori may regulate epilepsy susceptibility by inhibiting the NLRP3 inflammasome pathway,suggesting that Ori has a protective effect against epilepsy.