{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:03:48Z","timestamp":1791558228240,"version":"4.3.4"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T00:00:00Z","timestamp":1734912000000},"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>Introduction<\/jats:title><jats:p>Acute pancreatitis (AP) is a severe inflammatory disease of the pancreas that could trigger a systemic inflammation and multi-organ dysfunction. Stigmasterol, a natural plant sterol found in various herbs and vegetables, exhibits a significant anti-inflammatory, antioxidant, and cholesterol-lowering effects. However, its therapeutic potential in AP have not been thoroughly investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The present study employed network pharmacology combined with experimental verification to explore the protective effect of stigmasterol on AP and its molecular mechanism in a sodium taurocholate (STC)-induced AP mouse model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Protein-protein interaction (PPI) analysis pinpointed out MAPK3, also named as ERK1, as a promising stigmasterol target in AP therapy. Molecular docking analysis further revealed a strong binding capacity of stigmasterol to ERK1 (\u22126.57\u00a0kL\/mol). Furthermore, both <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> studies demonstrated that stigmasterol treatment notably attenuated STC-induced pancreatic injury, as evidented by decreased serum levels of lipase and amylase, improved systemic inflammation, and reduced acinar cell necrosis. At the molecular level, stigmasterol treatment exhibited a significant inhibition on STC-induced activation of ERK signaling pathway in pancreatic acinar cells, leading to the transition of acinar cell death from necrosis to apoptosis, thereby preventing acinar cell necrosis-induced systemic inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study demonstrated that stigmasterol exhibits a significant protective effect aganist AP, at least in part through enhancing acinar cell apoptosis via modulating the ERK signaling pathways.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2024.1485915","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T06:42:10Z","timestamp":1734936130000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Elucidating the mechanism of stigmasterol in acute pancreatitis treatment: insights from network pharmacology and in vitro\/in vivo experiments"],"prefix":"10.3389","volume":"15","author":[{"given":"Xuanlin","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ao","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuxian","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinrui","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyu","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang","family":"Xin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,12,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"354","DOI":"10.3389\/fpls.2019.00354","article-title":"Why do plants convert sitosterol to stigmasterol?","volume":"10","author":"Aboobucker","year":"2019","journal-title":"Front. 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