{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:57:37Z","timestamp":1790830657211,"version":"4.1.0"},"reference-count":77,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry for University and Research","award":["PE00060_3 PON03PE_00060_3"],"award-info":[{"award-number":["PE00060_3 PON03PE_00060_3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Natural products derived from the Mediterranean diet have attracted considerable interest as potential drug leads owing to their antioxidant and anti-inflammatory properties, as well as their beneficial effects on metabolic disorders such as non-alcoholic fatty liver disease (NAFLD). This study investigated the individual and combined effects of carvacrol, thymol, basil essential oil, and lycopene in an in vitro HepG2 model of hepatic steatosis. Their antioxidant activity was first confirmed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2\u2032-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical-scavenging assays. Treatments significantly reduced intracellular lipid accumulation and lipid peroxidation, as demonstrated by Oil Red O staining, LipidSpot\u2122 immunofluorescence, and the TBARS assay. In addition, the natural compounds restored lipid homeostasis by upregulating the \u03b2-oxidation- and lipolysis-related markers PPAR\u03b1, CPT1\u03b1, and ATGL, while downregulating PPAR\u03b3, a lipogenic regulator, and the pro-inflammatory enzyme 5-lipoxygenase. The combined formulation consistently exhibited the strongest biological activity, showing enhanced efficacy in reducing lipid accumulation, oxidative stress, and oxidative DNA damage, as evidenced by decreased 8-oxo-7,8-dihydroguanine (8-oxo-dG) formation. Overall, these results demonstrate that Mediterranean-diet-derived bioactives, particularly when used in combination, exert multitarget antioxidant activity by reducing oxidative damage, restoring lipid homeostasis, and modulating inflammatory pathways, supporting their potential application in natural product-based strategies for the prevention and management of NAFLD.<\/jats:p>","DOI":"10.3390\/molecules31193470","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T08:12:42Z","timestamp":1790669562000},"page":"3470","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bioactive Ingredients in the Mediterranean Diet for Hepatic Health: In Vitro Evaluation of Selected Extracts Against Non-Alcoholic Steatosis"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6891-9724","authenticated-orcid":false,"given":"Valentina","family":"Vassallo","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"},{"name":"Department of Life Sciences, Health and Health Professions, University of Study Link, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7989-3643","authenticated-orcid":false,"given":"Enrica","family":"Giustino","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosario","family":"Finamore","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1635-2724","authenticated-orcid":false,"given":"Antonietta","family":"Stellavato","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5019-2130","authenticated-orcid":false,"given":"Nicola","family":"Alessio","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariateresa","family":"Giuliano","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0909-7403","authenticated-orcid":false,"given":"Umberto","family":"Galderisi","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1066-843X","authenticated-orcid":false,"given":"Chiara","family":"Schiraldi","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s13668-023-00514-8","article-title":"Functional Food Chemical Ingredient Strategies for Non-alcoholic Fatty Liver Disease (NAFLD) and Hepatic Fibrosis: Chemical Properties, Health Benefits, Action, and Application","volume":"13","author":"Yu","year":"2024","journal-title":"Curr. 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