{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T09:11:10Z","timestamp":1765357870862,"version":"build-2065373602"},"reference-count":33,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hanyang university","award":["HY-202300000003033"],"award-info":[{"award-number":["HY-202300000003033"]}]},{"name":"the Korean Society of Ginseng","award":["HY-202300000003033"],"award-info":[{"award-number":["HY-202300000003033"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>(1) Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by liver damage similar to alcoholic fatty liver disease, including triglyceride infiltration of hepatocytes, regardless of alcohol consumption. It leads to progressive liver damage, such as loss of liver function, cirrhosis, and liver cancer, and the response rate of drugs under clinical research is less than 50%. There is an urgent need for biomarkers to evaluate the efficacy of these drugs. (2) Methods: MASLD was induced in mice using a High-Fat diet (HF), Western diet (WD), and Methionine\/Choline-Deficient diet (MCD) for 20 weeks (4 weeks for MCD). Liver tissue biopsies were performed, and the treatment effects of saponin and non-saponin feeds were evaluated. Fat accumulation and hepatic inflammation were measured, and mRNA sequencing analysis was conducted. The therapeutic effects were validated using patient-derived liver organoids. (3) Results: The NAFLD Activity Score (NAS) significantly increased in all MASLD models compared with controls. Saponin treatment decreased NAS in the HF and WD groups but not in the MCD group. RNA sequencing and PCA analysis showed that the HF saponin response samples were similar to normal controls. DAVID analysis revealed significant changes in lipid, triglyceride, and fatty acid metabolic processes. qRT-PCR confirmed decreased fibrosis markers in the HF saponin response group, and GSEA analysis showed reduced HAMP1 gene expression. (4) Conclusions: Among the diets, red ginseng was most effective in the HF diet, with significant effects in the saponin-treated group. The therapeutic efficacy was better when HAMP1 expression was increased. Therefore, we propose HAMP1 as a potential exploratory biomarker to assess the saponin response in a preclinical setting. In addition, the reduction of inflammation and hepatic iron accumulation suggests that saponins may exert antioxidant effects through modulation of oxidative stress.<\/jats:p>","DOI":"10.3390\/antiox14080943","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T10:58:26Z","timestamp":1754564306000},"page":"943","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Biomarker-Driven Optimization of Saponin Therapy in MASLD: From Mouse Models to Human Liver Organoids"],"prefix":"10.3390","volume":"14","author":[{"given":"Hye Young","family":"Kim","sequence":"first","affiliation":[{"name":"Hanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul 04763, Republic of Korea"},{"name":"Department of Internal Medicine, College of Medicine, Hanyang University, Seoul 04763, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2864-7677","authenticated-orcid":false,"given":"Ju Hee","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Institute of Women\u2019s Medical Life Science, Yonsei Cancer Center, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8935-7414","authenticated-orcid":false,"given":"Hyun Sung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, Hanyang University, Seoul 04763, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2875-6139","authenticated-orcid":false,"given":"Dae Won","family":"Jun","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Hanyang University, Seoul 04763, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101526","DOI":"10.1016\/j.clinre.2020.06.022","article-title":"Systematic review on the prevalence of nonalcoholic fatty liver disease in South Korea","volume":"45","author":"Im","year":"2021","journal-title":"Clin. 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