{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T17:51:20Z","timestamp":1790445080966,"version":"4.1.0"},"reference-count":51,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015826","name":"Korean Society of Ginseng","doi-asserted-by":"crossref","award":["2022"],"award-info":[{"award-number":["2022"]}],"id":[{"id":"10.13039\/501100015826","id-type":"DOI","asserted-by":"crossref"}]},{"award":["2022"],"award-info":[{"award-number":["2022"]}],"id":[{"id":"https:\/\/ror.org\/05v642w12","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["2022"],"award-info":[{"award-number":["2022"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"award":["2022"],"award-info":[{"award-number":["2022"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Korea Government, the Ministry of Science and ICT","doi-asserted-by":"publisher","award":["RS-2024-0040-8854"],"award-info":[{"award-number":["RS-2024-0040-8854"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Korea Government, the Ministry of Science and ICT","doi-asserted-by":"publisher","award":["RS-2026-25483999"],"award-info":[{"award-number":["RS-2026-25483999"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"award":["RS-2024-0040-8854"],"award-info":[{"award-number":["RS-2024-0040-8854"]}],"id":[{"id":"https:\/\/ror.org\/01wpjm123","id-type":"ROR","asserted-by":"publisher"}]},{"award":["RS-2026-25483999"],"award-info":[{"award-number":["RS-2026-25483999"]}],"id":[{"id":"https:\/\/ror.org\/01wpjm123","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Metabolic dysfunction-associated alcoholic liver disease (MetALD) is a serious worldwide health concern, exhibiting metabolic dysfunction-associated lipid accumulation, alcohol-associated oxidative damage, and endotoxin-induced inflammation. Rb1-enriched red ginseng saponin fraction (RGSF) has been known to exhibit anti-inflammatory and anti-oxidative properties, but its role in MetALD remains to be fully elucidated. This study aims to investigate the specific mechanism of RGSF in the MetALD mouse model. Methods: The MetALD mouse model was administered with or without Rb1-RGSF for 7 weeks. Histopathological and molecular analyses, along with primary cell isolation, were conducted for in vivo and ex vivo investigations. M1 macrophage polarization was assessed by analyzing pro-inflammatory cytokine expression. NF-kB\/p65 and TLR4 protein expression were measured before being visualized using immunofluorescence assays and confocal microscopy. Results: Histopathological examination revealed that RGSF treatment markedly reduced hepatic steatosis and attenuated inflammatory lesions in MetALD independent of oxidative stress. Notably, RGSF administration suppressed the LPS-induced internalization of surface TLR4. During the early inflammatory phase, RGSF prevented the LPS-mediated loss of the 130 kDa TLR4 form at the cell membrane, thereby limiting the generation of its 110 kDa cytoplasmic form. LPS-binding assay confirmed the direct interactions between TLR4 and RGSF. Conclusions: Collectively, these findings demonstrate that RGSF regulates TLR4 expression and trafficking, leading to the suppression of M1 macrophage polarization by inhibiting LPS\u2013TLR4 surface interactions, thus exhibiting hepatoprotective effects.<\/jats:p>","DOI":"10.3390\/nu18142294","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:55:21Z","timestamp":1783990521000},"page":"2294","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ginsenoside Rb1-Enriched Saponin Fraction Inhibits M1 Macrophage Polarization by Suppression of TLR4 Trafficking in Metabolic Dysfunction-Associated Alcoholic Liver Disease"],"prefix":"10.3390","volume":"18","author":[{"given":"Tae-Un","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Veterinary Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Hyuk","family":"Yim","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo Jun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seoung-Woo","family":"Lee","sequence":"additional","affiliation":[{"name":"Core Protein Resources Center, Daegu-Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Yeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Core Protein Resources Center, Daegu-Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung-Ku","family":"Kang","sequence":"additional","affiliation":[{"name":"Preclinical Research Center, K-MEDI Hub, Daegu 41061, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7817-2222","authenticated-orcid":false,"given":"Min-Soo","family":"Seo","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea"},{"name":"Institute for Veterinary Biomedical Science, Kyungpook National University, Daegu 41566, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3088-1318","authenticated-orcid":false,"given":"Man Hee","family":"Rhee","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea"},{"name":"Institute for Veterinary Biomedical Science, Kyungpook National University, Daegu 41566, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Min","family":"Baek","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea"},{"name":"Institute for Veterinary Biomedical Science, Kyungpook National University, Daegu 41566, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0233-4114","authenticated-orcid":false,"given":"Seong-Kyoon","family":"Choi","sequence":"additional","affiliation":[{"name":"Core Protein Resources Center, Daegu-Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4876-1055","authenticated-orcid":false,"given":"Jin-Kyu","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea"},{"name":"Institute for Veterinary Biomedical Science, Kyungpook National University, Daegu 41566, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1097\/HEP.0000000000000520","article-title":"A multi-society Delphi consensus statement on new fatty liver disease nomenclature","volume":"78","author":"Rinella","year":"2023","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"969","DOI":"10.3350\/cmh.2023.0359","article-title":"From 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