{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T22:42:14Z","timestamp":1785451334813,"version":"3.56.0"},"reference-count":101,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"crossref","award":["82304985"],"award-info":[{"award-number":["82304985"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"crossref","award":["82505300"],"award-info":[{"award-number":["82505300"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"crossref","award":["82270672"],"award-info":[{"award-number":["82270672"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Program of Science and Technology Department of Sichuan Province","award":["2025ZNSFSC1794"],"award-info":[{"award-number":["2025ZNSFSC1794"]}]},{"name":"Program of Science and Technology Department of Sichuan Province","award":["2025ZNSFSC1797"],"award-info":[{"award-number":["2025ZNSFSC1797"]}]},{"name":"Postdoctoral Research Fund of West China Hospital, Sichuan University","award":["2023HXBH087"],"award-info":[{"award-number":["2023HXBH087"]}]},{"name":"Postdoctoral Research Fund of West China Hospital, Sichuan University","award":["2024HXBH087"],"award-info":[{"award-number":["2024HXBH087"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Acute pancreatitis (AP) is a severe inflammatory disorder characterized by a complex molecular pathophysiology involving premature zymogen activation, organelle dysfunction, and systemic immune dysregulation. Current therapeutic strategies remain largely supportive, underscoring the critical need for specific molecular-targeted interventions. Baicalein, a bioactive flavonoid derived from Scutellaria baicalensis Georgi, has emerged as a potent pleiotropic agent. This review comprehensively synthesizes the molecular mechanisms underlying baicalein\u2019s therapeutic efficacy in AP. Its capacity to intercept the pathological cascade at multiple checkpoints is elucidated, from mitigating the initiating cytosolic calcium overload and preserving mitochondrial integrity to suppressing the cytokine storm via the TLR4\/NF-\u03baB\/MAPK signaling axis. Crucially, baicalein modulates the pancreatic immune microenvironment by driving the phenotypic polarization of macrophages from pro-inflammatory M1 to reparative M2 states and regulating neutrophil dynamics, specifically by inhibiting infiltration and neutrophil extracellular trap formation. Furthermore, its role in orchestrating regulated cell death pathways is highlighted, specifically by blocking pyroptosis and ferroptosis while modulating apoptosis, and its function as a biophysical scavenger of circulating histones and pancreatic lipase to neutralize systemic toxins. Consequently, this review emphasizes the multi-target biological activities of baicalein, providing a mechanistic rationale for its development as a precision therapeutic candidate for AP.<\/jats:p>","DOI":"10.3390\/biom16010151","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T15:12:04Z","timestamp":1768403524000},"page":"151","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Molecular Mechanisms and Therapeutic Potential of Baicalein in Acute Pancreatitis: A Comprehensive Review"],"prefix":"10.3390","volume":"16","author":[{"given":"Linbo","family":"Yao","sequence":"first","affiliation":[{"name":"West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyu","family":"Liu","sequence":"additional","affiliation":[{"name":"West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8659-322X","authenticated-orcid":false,"given":"Wei","family":"Huang","sequence":"additional","affiliation":[{"name":"West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"West China Biobank, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinmin","family":"Yang","sequence":"additional","affiliation":[{"name":"West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1001\/jama.2020.20317","article-title":"Acute Pancreatitis: A Review","volume":"325","author":"Mederos","year":"2021","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1053\/j.gastro.2021.09.043","article-title":"Global Incidence of Acute Pancreatitis Is Increasing Over Time: A Systematic Review and Meta-Analysis","volume":"162","author":"Iannuzzi","year":"2022","journal-title":"Gastroenterology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1038\/s41575-019-0158-2","article-title":"New insights into acute pancreatitis","volume":"16","author":"Lee","year":"2019","journal-title":"Nat. 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