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Recent studies have shown that SA has potential anti-seizure properties due to its anti-inflammatory, antioxidant, and anti-apoptotic effects. The present study investigated the neuroprotective role of SA at two different dosages in a pentylenetetrazol (PTZ)-induced acute seizure model. Mice were divided into six groups: normal control, PTZ, SA (20\u00a0mg\/kg), SA (20\u00a0mg\/kg)\u2009+\u2009PTZ, SA (40\u00a0mg\/kg), and SA (40\u00a0mg\/kg)\u2009+\u2009PTZ. SA was orally administered for 21\u00a0days, followed by a convulsive dose of intraperitoneal PTZ (50\u00a0mg\/kg). Seizures were estimated via the Racine scale, and animals were behaviorally tested using the Y-maze. Brain tissues were used to assess the levels of GABA, glutamate, oxidative stress markers, calcium, calcineurin, (Nod)-like receptor protein-3 (NLRP3), interleukin (IL)-1\u03b2, apoptosis-associated speck-like protein (ASC), Bcl-2\u2013associated death protein (Bad) and Bcl-2. Molecular docking of SA using a multistep <jats:italic>in silico<\/jats:italic> protocol was also performed. The results showed that SA alleviated oxidative stress, restored the GABA\/glutamate balance and calcium\/calcineurin signaling, downregulated NLRP3 and apoptosis, and improved recognition and ambulatory activity in PTZ-treated mice. <jats:italic>In silico<\/jats:italic> results also revealed that SA strongly interacts with the target proteins NLRP3 and ASC. Overall, the results suggest that SA is a promising antiseizure agent and that both doses of SA are comparable, with 40\u00a0mg\/kg SA being superior in normalizing glutathione, calcium and IL-1\u03b2, in addition to calcineurin, NLRP3, ASC and Bad.<\/jats:p>\n                <jats:p><jats:bold>Graphical Abstract<\/jats:bold><\/jats:p>","DOI":"10.1007\/s10753-024-02019-0","type":"journal-article","created":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T13:02:36Z","timestamp":1714050156000},"page":"1969-1986","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Sinapic Acid Mitigates Pentylenetetrazol-induced Acute Seizures By Modulating the NLRP3 Inflammasome and Regulating Calcium\/calcineurin Signaling: In Vivo and In Silico Approaches"],"prefix":"10.1007","volume":"47","author":[{"given":"Shimaa O.","family":"Ali","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heba R.","family":"Ghaiad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghada F.","family":"Elmasry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noha A.","family":"Mehana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,25]]},"reference":[{"key":"2019_CR1","doi-asserted-by":"publisher","DOI":"10.1159\/000503831","author":"E Beghi","year":"2020","unstructured":"Beghi, E. 2020. 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