{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T15:13:49Z","timestamp":1780499629380,"version":"3.54.1"},"reference-count":80,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T00:00:00Z","timestamp":1723766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004488","name":"Croatian Ministry of Science and Education","doi-asserted-by":"publisher","award":["IP5-FDMZ-2023"],"award-info":[{"award-number":["IP5-FDMZ-2023"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004488","name":"Croatian Ministry of Science and Education","doi-asserted-by":"publisher","award":["IP6-FDMZ-2023"],"award-info":[{"award-number":["IP6-FDMZ-2023"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Abstract: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is becoming more prominent globally due to an increase in the prevalence of obesity, dyslipidemia, and type 2 diabetes. A great deal of studies have proposed potential treatments for MASLD, with few of them demonstrating promising results. The aim of this study was to investigate the potential effects of (-)-epicatechin (EPI) on the development of MASLD in an in vitro model using the HepG2 cell line by determining the metabolic viability of the cells and the levels of PPAR\u03b1, PPAR\u03b3, and GSH. HepG2 cells were pretreated with 10, 30, 50, and 100 \u03bcM EPI for 4 h to assess the potential effects of EPI on lipid metabolism. A MASLD cell culture model was established using HepG2 hepatocytes which were exposed to 1.5 mM oleic acid (OA) for 24 h. Moreover, colorimetric MTS assay was used in order to determine the metabolic viability of the cells, PPAR\u03b1 and PPAR\u03b3 protein levels were determined using enzyme-linked immunosorbent assay (ELISA), and lipid accumulation was visualized using the Oil Red O Staining method. Also, the levels of intracellular glutathione (GSH) were measured to determine the level of oxidative stress. EPI was shown to increase the metabolic viability of the cells treated with OA. The metabolic viability of HepG2 cells, after 24 h incubation with OA, was significantly decreased, with a metabolic viability of 71%, compared to the cells pretreated with EPI, where the metabolic viability was 74\u201386% with respect to the concentration of EPI used in the experiment. Furthermore, the levels of PPAR\u03b1, PPAR\u03b3, and GSH exhibited a decrease in response to increasing EPI concentrations. Pretreatment with EPI has demonstrated a great effect on the levels of PPAR\u03b1, PPAR\u03b3, and GSH in vitro. Therefore, considering that EPI mediates lipid metabolism in MASLD, it should be considered a promising hepatoprotective agent in future research.<\/jats:p>","DOI":"10.3390\/cimb46080531","type":"journal-article","created":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T12:40:07Z","timestamp":1723812007000},"page":"8981-8994","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Green Tea Polyphenol (-)-Epicatechin Pretreatment Mitigates Hepatic Steatosis in an In Vitro MASLD Model"],"prefix":"10.3390","volume":"46","author":[{"given":"Marija","family":"Hefer","sequence":"first","affiliation":[{"name":"Department of Translational Medicine, Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Petrovic","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0079-2349","authenticated-orcid":false,"given":"Lucija Kuna","family":"Roguljic","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tea Omanovic","family":"Kolaric","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Biochemistry, Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2523-6007","authenticated-orcid":false,"given":"Tomislav","family":"Kizivat","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and Oncology, Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine H.","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7041-5445","authenticated-orcid":false,"given":"Ashraf A.","family":"Tabll","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Smolic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Biochemistry, Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0512-462X","authenticated-orcid":false,"given":"Aleksandar","family":"Vcev","sequence":"additional","affiliation":[{"name":"Department of Integrative Medicine, Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6867-826X","authenticated-orcid":false,"given":"Martina","family":"Smolic","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1038\/s41591-018-0104-9","article-title":"Mechanisms of NAFLD development and therapeutic strategies","volume":"24","author":"Friedman","year":"2018","journal-title":"Nat. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Pouwels, S., Sakran, N., Graham, Y., Leal, A., Pintar, T., Yang, W., Kassir, R., Singhal, R., Mahawar, K., and Ramnarain, D. (2022). Non-alcoholic fatty liver disease (NAFLD): A review of pathophysiology, clinical management and effects of weight loss. BMC Endocr. 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