{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T20:07:55Z","timestamp":1766088475459,"version":"3.41.2"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T00:00:00Z","timestamp":1745366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Tetramethylpyrazine (TMPZ), an active alkaloid derived from traditional Chinese medicine, has shown anti-inflammatory and anti-pyroptotic properties. However, its role in acute pancreatitis (AP)-induced pyroptosis remains unclear. This study aims to investigate the effects of TMPZ on AP-induced pyroptosis and its potential mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>A cerulein-induced AP rat model was used to evaluate TMPZ\u2019s protective effects <jats:italic>in vivo<\/jats:italic>, and its mechanisms were explored using AR42J\u00a0cells <jats:italic>in vitro<\/jats:italic>. Pancreatic injury was assessed by hematoxylin-eosin staining, TUNEL assay, and serum biochemistry. Transmission electron microscopy, immunofluorescence, Western blotting, and quantitative real-time polymerase chain reaction (RT-qPCR) were conducted to examine pyroptosis and related signaling pathways. Cytotoxicity and apoptosis were measured by CCK-8, LDH assays, and Hoechst 33342\/PI staining. The role of NRF2 in TMPZ\u2019s effects was further evaluated using NRF2 siRNA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>TMPZ alleviated pancreatic histopathological damage, reduced apoptosis, and decreased serum amylase levels and pro-inflammatory cytokines (IL-1\u03b2, IL-18). TMPZ also suppressed pyroptosis by inhibiting NLRP3 inflammasome activation and downregulating pyroptosis-related proteins (NLRP3,caspase-1, ASC, GSDMD) while upregulating NRF2 and HO-1 expression. NRF2 siRNA attenuated TMPZ\u2019s anti-inflammatory and pyroptosis-inhibitory effects, confirming the involvement of the NRF2 pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>TMPZ mitigates AP-induced inflammation and injury by modulating pyroptosis via the NRF2 signaling pathway. These findings suggest TMPZ\u2019s therapeutic potential for AP.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1557681","type":"journal-article","created":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T07:40:15Z","timestamp":1746085215000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Tetramethylpyrazine alleviates acute pancreatitis inflammation by inhibiting pyroptosis via the NRF2 pathway"],"prefix":"10.3389","volume":"16","author":[{"given":"Huangen","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minglian","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongling","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingqing","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youpei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaotong","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiwen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1007\/s10495-022-01729-w","article-title":"Pyroptosis in acute pancreatitis and its therapeutic regulation","volume":"27","author":"Al Mamun","year":"2022","journal-title":"Apoptosis"},{"key":"B2","doi-asserted-by":"publisher","first-page":"116920","DOI":"10.1016\/j.jep.2023.116920","article-title":"Chaiqin chengqi decoction alleviates acute pancreatitis by targeting gasdermin D-mediated pyroptosis","volume":"318","author":"Cao","year":"2024","journal-title":"J. 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