{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T03:19:05Z","timestamp":1790479145896,"version":"4.1.0"},"reference-count":39,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T00:00:00Z","timestamp":1663286400000},"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":["2017R1A5A2015385"],"award-info":[{"award-number":["2017R1A5A2015385"]}]},{"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":["2022R1A4A10189001"],"award-info":[{"award-number":["2022R1A4A10189001"]}]},{"name":"National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT)","award":["HI15C0001"],"award-info":[{"award-number":["HI15C0001"]}]},{"name":"Korea Health Technology R&amp;D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Korea","award":["2017R1A5A2015385"],"award-info":[{"award-number":["2017R1A5A2015385"]}]},{"name":"Korea Health Technology R&amp;D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Korea","award":["2020R1A2C1004131"],"award-info":[{"award-number":["2020R1A2C1004131"]}]},{"name":"Korea Health Technology R&amp;D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Korea","award":["2022R1A4A10189001"],"award-info":[{"award-number":["2022R1A4A10189001"]}]},{"name":"Korea Health Technology R&amp;D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Korea","award":["HI15C0001"],"award-info":[{"award-number":["HI15C0001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sepsis is an uncontrolled response to inflammatory infection and is associated with high levels of mortality and morbidity. Rg4 is a rare ginsenoside mainly found in the leaves of Panax ginseng C. A. Meyer and the major protopanaxatriol-type ginsenoside of black ginseng. In this study, we determined whether Rg4 affects cecal ligation and puncture (CLP)-induced sepsis. Animals were separated into the following six groups: control group, CLP-operated group, CLP plus maslinic acid (MA), and CLP plus Rg4 (5, 10, or 15 mg\/kg). Survival rate, body weight changes, inflammatory cytokines, and histological analyses were assessed. Human endothelial cells were activated with the high-mobility group box 1 (HMGB1) protein and Rg4. Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Enzyme-linked immunosorbent assay (ELISA) and Western blot analysis were used to assess inflammation and gene expression, respectively. After CLP surgery, the Rg4-administered group exhibited a higher survival rate and body weight compared with the untreated control group. Rg4 treatment reduced cytokine levels, including tumor necrosis factor (TNF)-\u03b1 and interleukin (IL)-1\u03b2, as well as nitric oxide (NO) levels and renal inflammation. After Rg4 treatment of HMGB1-activated cells, the expressions of toll-like receptor (TLR) 4 and TNF-\u03b1 were decreased, and the activation of phosphoinositide 3-kinase (PI3K)\/AKT signaling increased cell viability. In summary, Rg4 inhibited inflammation and exhibited a protective effect against CLP-induced sepsis, thereby reinforcing cell survival against septic responses.<\/jats:p>","DOI":"10.3390\/ijms231810836","type":"journal-article","created":{"date-parts":[[2022,9,18]],"date-time":"2022-09-18T23:39:22Z","timestamp":1663544362000},"page":"10836","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Inhibitory Activities of Rare Ginsenoside Rg4 on Cecal Ligation and Puncture-Induced Sepsis"],"prefix":"10.3390","volume":"23","author":[{"given":"Go Oun","family":"Kim","sequence":"first","affiliation":[{"name":"Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 41566, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nayeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 41566, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyu Yong","family":"Song","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejon 34134, 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, 80 Daehak-ro, Buk-gu, Daegu 41566, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10619","DOI":"10.3390\/molecules161210619","article-title":"The in vitro structure-related anti-cancer activity of ginsenosides and their derivatives","volume":"16","author":"Dong","year":"2011","journal-title":"Molecules"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.4049\/jimmunol.148.5.1519","article-title":"Saponin adjuvant enhancement of antigen-specific immune responses to an experimental HIV-1 vaccine","volume":"148","author":"Wu","year":"1992","journal-title":"J. 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