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EEG recording and behavioral tests were used to evaluate the disease\u2010modifying effects of TPL in epileptic conditions. Extracellular recording combined with optogenetics was used to evaluate the effect of TPL on hippocampal GABAergic inhibition in\u00a0vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Though intragastric administration of TPL (50\u2009\u03bcg\/kg) had no direct anticonvulsive effect in normal mice, it retarded corneal kindling acquisition in mice and reduced the seizure severity in corneal kindled mice. Meanwhile, intragastric administration (10 or 50\u2009\u03bcg\/kg) of TPL exhibited disease\u2010modifying effects in the established KA mouse model of temporal lobe epilepsy (TLE). Extracellular recording combined with optogenetics showed that TPL improved the hippocampal GABAergic \u201cbraking effect\u201d in epileptic mice. Furthermore, bioinformatics analysis predicts IL\u20101\u03b2 as a key target for the antiepileptic effect of TPL. TPL reduced the level of IL\u20101\u03b2 in the hippocampus of KA\u2010induced epileptic mice, while focal injection of IL\u20101\u03b2 (5\u2009ng in 1\u2009\u03bcL saline) attenuated the hippocampal GABAergic \u201cbraking effect\u201d in normal mice. Focal injection of TPCA\u20101 (an IKK\u20102\/NF\u2010\u03baB inhibitor, 600\u2009ng in 1\u2009\u03bcL 1% DMSO) partly recovered the IL\u20101\u03b2\u2010induced attenuation of the GABAergic \u201cbraking effect\u201d.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study indicates that a low dose of TPL may inhibit epilepsy by potentially rescuing dysfunction in hippocampal GABAergic neural circuits related to neuroinflammation in mice.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70586","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T07:31:58Z","timestamp":1756452718000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Triptolide Inhibits Epileptic Seizures by Rescuing the Neuroinflammation\u2010Related GABAergic Dysfunction in Mice"],"prefix":"10.1111","volume":"31","author":[{"given":"Haimei","family":"Lu","sequence":"first","affiliation":[{"name":"Research Institute of Chinese Medical Clinical Foundation and Immunology &amp; 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