{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T16:31:20Z","timestamp":1790353880796,"version":"4.1.0"},"reference-count":58,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T00:00:00Z","timestamp":1679529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Program of Shanghai Municipal Commission of Health and Family Planning","award":["ZY (2021-2023)-0215"],"award-info":[{"award-number":["ZY (2021-2023)-0215"]}]},{"name":"The Program of Shanghai Municipal Commission of Health and Family Planning","award":["ZYYCXTD-D-202004"],"award-info":[{"award-number":["ZYYCXTD-D-202004"]}]},{"name":"Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine","award":["ZY (2021-2023)-0215"],"award-info":[{"award-number":["ZY (2021-2023)-0215"]}]},{"name":"Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine","award":["ZYYCXTD-D-202004"],"award-info":[{"award-number":["ZYYCXTD-D-202004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Septic shock is defined as a subset of sepsis, which is associated with a considerably high mortality risk. The caspase-11 non-canonical inflammasome is sensed and activated by intracellular lipopolysaccharide (LPS) leading to pyroptosis, it plays a critical role in septic shock. However, there are few known drugs that can control caspase-11 non-canonical inflammasome activation. We report here that goitrin, an alkaloid from Radix Isatidis, shows protective effects in LPS-induced septic shock and significant inhibitory effect in caspase-11 non-canonical inflammasome pathway. Male C57BL\/6J were injected intraperitoneally with LPS (20 mg\/kg) to induce experimental septic shock. The results demonstrated that the survival rates of mice pretreated with goitrin or Toll-like receptor 4 (TLR4) inhibitor TKA-242 increased, and LPS-induced hypothermia and lung damage improved by inhibiting inflammatory response. Elucidating the detailed mechanism, we surprisingly found goitrin is really different from TAK-242, it independent of the TLR4 signal activation, but significantly inhibited the activation of caspase-11 non-canonical inflammasome, including cleaved caspase-11 and N-terminal fragment of gasdermin D (GSDMD-NT). Furthermore, with a nonlethal dose of the TLR3 agonist poly(I:C)-primed and subsequently challenged with LPS to induce caspase-11-mediated lethal septic shock, the efficacy of goitrin had been verified. Those results revealed the effect of goitrin in protective against LPS-induced septic shock via inhibiting caspase-11 non-canonical inflammasome, which provided a new therapeutic strategy for clinical treatment of septic shock.<\/jats:p>","DOI":"10.3390\/molecules28072883","type":"journal-article","created":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T05:19:24Z","timestamp":1679548764000},"page":"2883","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Protective Effects of Goitrin on LPS-Induced Septic Shock in C57BL\/6J Mice via Caspase-11 Non-Canonical Inflammasome Inhibition"],"prefix":"10.3390","volume":"28","author":[{"given":"Deqing","family":"Ruan","sequence":"first","affiliation":[{"name":"School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"},{"name":"Shanghai Key Laboratory of Compound Chinese Medicines and The Ministry of Education (MOE) Key Laboratory of Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"},{"name":"Department of Molecular Pharmacology, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"},{"name":"Shanghai Key Laboratory of Compound Chinese Medicines and The Ministry of Education (MOE) Key Laboratory of Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianfei","family":"Luo","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Shi","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Compound Chinese Medicines and The Ministry of Education (MOE) Key Laboratory of Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Ding","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Compound Chinese Medicines and The Ministry of Education (MOE) Key Laboratory of Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengtao","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Compound Chinese Medicines and The Ministry of Education (MOE) Key Laboratory of Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yang","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Compound Chinese Medicines and The Ministry of Education (MOE) Key Laboratory of Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"},{"name":"Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1177\/0885066617711882","article-title":"Epidemiology and Changes in Mortality of Sepsis After the Implementation of Surviving Sepsis Campaign Guidelines","volume":"34","author":"Andaluz","year":"2019","journal-title":"J. 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