{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T08:24:55Z","timestamp":1784795095944,"version":"3.55.0"},"reference-count":40,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T00:00:00Z","timestamp":1709510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT)","award":["2020R1A2C1004131"],"award-info":[{"award-number":["2020R1A2C1004131"]}]},{"name":"National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT)","award":["RS-2023-00259081"],"award-info":[{"award-number":["RS-2023-00259081"]}]},{"name":"Korea Drug Development Fund funded by Ministry of Science and ICT, Ministry of Trade, In-dustry, and Energy, and Ministry of Health and Welfare","award":["2020R1A2C1004131"],"award-info":[{"award-number":["2020R1A2C1004131"]}]},{"name":"Korea Drug Development Fund funded by Ministry of Science and ICT, Ministry of Trade, In-dustry, and Energy, and Ministry of Health and Welfare","award":["RS-2023-00259081"],"award-info":[{"award-number":["RS-2023-00259081"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>High mobility group box 1 (HMGB1), a protein with important functions, has been recognized as a potential therapeutic target for the treatment of sepsis. One possible mechanism for this is that inhibiting HMGB1 secretion can exert antiseptic effects, which can restore the integrity of the vascular barrier. (7S)-(+)-cyclopentyl carbamic acid 8,8-dimethyl-2-oxo-6,7-dihydro-2H,8H-pyrano[3,2-g]chromen-7-yl-ester (CGK012) is a newly synthesized pyranocoumarin compound that could function as a novel small-molecule inhibitor of the Wnt\/\u03b2-catenin signaling pathway. However, no studies have yet determined the effects of CGK012 on sepsis. We investigated the potential of CGK012 to attenuate the excessive permeability induced by HMGB1 and enhance survival rates in a mouse model of sepsis with reduced HMGB1 levels following lipopolysaccharide (LPS) treatment. In both LPS-stimulated human endothelial cells and a mouse model exhibiting septic symptoms due to cecal ligation and puncture (CLP), we assessed proinflammatory protein levels and tissue damage biomarkers as indicators of reduced vascular permeability. CGK012 was applied after induction in human endothelial cells exposed to LPS and the CLP-induced mouse model of sepsis. CGK012 effectively mitigated excessive permeability and suppressed HMGB1 release, resulting in improved vascular stability, decreased mortality, and enhanced histological conditions in the mouse model of CLP-induced sepsis. In conclusion, our findings indicate that CGK012 treatment in mice with CLP-induced sepsis diminished HMGB1 release and increased the survival rate, suggesting its potential as a pharmaceutical intervention for sepsis.<\/jats:p>","DOI":"10.3390\/ijms25052976","type":"journal-article","created":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T08:03:47Z","timestamp":1709539427000},"page":"2976","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Antiseptic Functions of CGK012 against HMGB1-Mediated Septic Responses"],"prefix":"10.3390","volume":"25","author":[{"given":"Yun Jin","family":"Park","sequence":"first","affiliation":[{"name":"Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, Daegu 41566, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0827-6960","authenticated-orcid":false,"given":"Jong Beom","family":"Heo","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungnam National University, Daejon 34134, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2328-1493","authenticated-orcid":false,"given":"Yoon-Jung","family":"Choi","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungnam National University, Daejon 34134, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanghee","family":"Cho","sequence":"additional","affiliation":[{"name":"Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, Daegu 41566, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taeho","family":"Lee","sequence":"additional","affiliation":[{"name":"Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, Daegu 41566, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyu Yong","family":"Song","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungnam National University, Daejon 34134, Republic of Korea"},{"name":"AREZ Co., Ltd., Daejeon 34036, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5756-9367","authenticated-orcid":false,"given":"Jong-Sup","family":"Bae","sequence":"additional","affiliation":[{"name":"Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, Daegu 41566, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16045","DOI":"10.1038\/nrdp.2016.45","article-title":"Sepsis and septic shock","volume":"2","author":"Hotchkiss","year":"2016","journal-title":"Nat. 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