{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:46:06Z","timestamp":1787013966961,"version":"build-2736575974"},"reference-count":54,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82204409"],"award-info":[{"award-number":["82204409"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373910"],"award-info":[{"award-number":["82373910"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Sepsis, caused by pathogen infection, poses a serious threat to human life. While the link between sepsis and pyroptosis via Caspase\u201011 non\u2010canonical inflammasome activation is known, effective treatments remain lacking. Previous studies have confirmed that GL\u2010V9 has antifibrotic and antitumor activities, but whether it has a therapeutic effect on sepsis is unclear. The aim of this study was to investigate the anti\u2010inflammatory activity of GL\u2010V9 and its possible mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>The caecal ligation and puncture (CLP) model was used to assess the antiseptic effects of GL\u2010V9 in vivo. Mouse bone marrow derived macrophages (BMDMs) and murine macrophages line J774A.1 also served as an in vitro Caspase\u201011 activation induced pyroptosis model. Cellular functions and molecular mechanism were analysed using cell viability assay, PI uptake assay, western blotting, immunofluorescence and co\u2010immunoprecipitation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      GL\u2010V9 reduced tissue damage and mortality in mice with sepsis, and decreased the secretion of inflammatory factors in vivo. In vitro\n                      <jats:italic>,<\/jats:italic>\n                      GL\u2010V9 suppressed Caspase\u201011\u2010induced pyroptosis and prevented the release of LPS from early endosomes. Mechanistic studies revealed that GL\u2010V9 limits Caspase\u201011 activation by inhibiting ALOX12\u2010mediated lipid peroxidation. Further studies confirmed that GL\u2010V9 did not further alleviate the symptoms and inflammatory response of septic mice in\n                      <jats:italic>Alox12<\/jats:italic>\n                      deficient mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>GL\u2010V9 exerts a powerful anti\u2010sepsis effect in vivo, which is associated with the inhibition of Caspase\u201011 activation. Mechanistically, GL\u2010V9 may block LPS release from early endosomes by inhibiting ALOX12\u2010mediated lipid peroxidation. This suggests that GL\u2010V9 is a potential candidate for the treatment of sepsis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70053","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T19:59:46Z","timestamp":1744747186000},"page":"3767-3785","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["GL\u2010V9 inhibits Caspase\u201011 activation\u2010induced pyroptosis by suppressing ALOX12\u2010mediated lipid peroxidation to alleviate sepsis"],"prefix":"10.1111","volume":"182","author":[{"given":"Li","family":"Chen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Physiology, School of Basic Medicine and Clinical Pharmacy China Pharmaceutical University  Nanjing People's Republic of 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