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The prior studies demonstrated its protection against neuroinflammation, dopaminergic neuron loss, and in the treatment of ischemic stroke, but its anticonvulsive efficacy against epilepsy remains elusive. The aim of this study was to examine antiepileptic effects of Hua\u2010Feng\u2010Dan recipes and the mechanism of protection. Pentylenetetrazol (PTZ)\u2010induced kindling mouse model (35\u2009mg\/kg, ip on alternate\u2009days \u00d7 10) was used to evaluate the antiepileptic effects of Hua\u2010Feng\u2010Dan recipes. Mice were given original, reduced, and nonfermented Hua\u2010Feng\u2010Dan via feed at clinical dose (0.5\u2009g\/kg) and diazepam was used as a positive control. The seizure scores were recorded after each PTZ injection. At the end of the experiments, the brain and colon content were collected for RNA\u2010Seq and 16S rRNA\u2010Seq, respectively, followed by bioinformatics and qPCR verification. Hua\u2010Feng\u2010Dan recipes were effective against PTZ\u2010induced seizures, with original the best and half of reduced (0.25\u2009g\/kg) ineffective. PTZ\u2010induced aberrant gene expressions in the brain were ameliorated by Hua\u2010Feng\u2010Dan recipes to various extents. Ingenuity Pathway Analysis of differentially expressed genes revealed that PTZ\u2010altered canonical pathways and upstream regulators were attenuated by Hua\u2010Feng\u2010Dan treatments. qPCR verified the expression of early immediate genes, proinflammatory mediators, transporters and apoptosis genes. PTZ\u2010disrupted gut microbiome was also ameliorated by Hua\u2010Feng\u2010Dan recipes, and the modulation of\n                    <jats:italic>Lachnospiraceae<\/jats:italic>\n                    and ASV230 was consistent with the literature. Hua\u2010Feng\u2010Dan recipes were effective against PTZ\u2010induced kindling mice. The mechanisms appeared to be related to the modulation of brain gene expression and gut microbiota.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:list list-type=\"explicit-label\">\n                      <jats:list-item>\n                        <jats:p>Hua\u2010Feng\u2010Dan (HFD) recipes were effective against PTZ\u2010induced seizures in mice.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>HFD ameliorated abnormal brain gene expressions in PTZ kindling mice via RNA sequencing (RNA\u2010seq).<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>IPA of DEGs revealed improved canonical pathways and upstream regulators.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>16S rRNA\u2010seq showed microbiome modulation by HFD in PTZ kindling mice.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>qPCR verified selected brain genes and bacterial ASVs.<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:p>","DOI":"10.1155\/bmri\/5336509","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T18:11:48Z","timestamp":1774721508000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antiepileptic Effects of Hua\u2010Feng\u2010Dan Against Pentylenetetrazol\u2010Induced Seizures in 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