{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:37:44Z","timestamp":1787495864596,"version":"build-2736575974"},"reference-count":61,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Non-alcoholic fatty liver disease (NAFLD) is a major metabolic disorder characterized by hepatic lipid accumulation, oxidative stress, and disturbance of lysosomal degradation. Central to these processes is glutathione (GSH), a key antioxidant regulating redox balance and cellular homeostasis. This study aimed to evaluate the therapeutic potential of two dietary antioxidants\u2014astaxanthin and Garcinia indica (kokum)\u2014in modulating hepatic redox status, lysosomal function, and metabolic gene expression in a murine model of diet-induced NAFLD. A total of 120 male Swiss Webster mice were allocated into control and steatotic groups, followed by a 90-day supplementation period with astaxanthin, kokum, or their combination. Liver tissue was collected post-supplementation for biochemical, antioxidant, and qRT-PCR analyses. Outcomes included lysosomal enzymes activities, superoxide dismutase (SOD), GSH, vitamin C, total polyphenols, DPPH radical-scavenging activity, and total antioxidant capacity (TAC). NAFLD induced marked oxidative stress, lysosomal overactivation, and alteration of antioxidant-related gene expression. Combined supplementation restored GSH, enhanced TAC, reduced lysosomal stress markers, and significantly upregulated nuclear factor erythroid 2-related factor 2 (Nfe2l2) while downregulating fatty acid synthase (FASN) and partially rescuing lipoprotein lipase (LpL). Correlation analyses revealed strong associations between antioxidant capacity, lysosomal function, and transcriptional regulation, supporting the therapeutic relevance of combined antioxidant therapy for concurrent redox and lysosomal dysregulation in NAFLD. These findings underscore the therapeutic potential of targeting redox and cellular degradation pathways with antioxidant-based interventions to re-establish hepatic metabolic balance in NAFLD and related disorders.<\/jats:p>","DOI":"10.3390\/molecules31020321","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T09:57:02Z","timestamp":1768816622000},"page":"321","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Antioxidant Intervention in NAFLD: Astaxanthin and Kokum Modulate Redox Status and Lysosomal Degradation"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2324-7911","authenticated-orcid":false,"given":"Natalia","family":"Ksepka","sequence":"first","affiliation":[{"name":"Department of Biotechnology and Nutrigenomics, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Post\u0119pu 36a, Jastrz\u0119biec, 05-552 Magdalenka, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9103-6111","authenticated-orcid":false,"given":"Natalia","family":"Kuzia","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Nutrigenomics, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Post\u0119pu 36a, Jastrz\u0119biec, 05-552 Magdalenka, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8810-0003","authenticated-orcid":false,"given":"Sara","family":"Frazzini","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Animal Sciences-DIVAS, University of Milan, Via dell\u2019Universit\u00e0 6, 26900 Lodi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1178-4683","authenticated-orcid":false,"given":"Luciana","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Animal Sciences-DIVAS, University of Milan, Via dell\u2019Universit\u00e0 6, 26900 Lodi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0327-3202","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"\u0141ysek-G\u0142adysi\u0144ska","sequence":"additional","affiliation":[{"name":"Division of Medical Biology, Institute of Biology, University of Jan Kochanowski, 25-406 Kielce, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6129-7723","authenticated-orcid":false,"given":"Micha\u0142","family":"\u0141awi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Nutrigenomics, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Post\u0119pu 36a, Jastrz\u0119biec, 05-552 Magdalenka, Poland"},{"name":"Department of General, Gastroenterology, and Oncologic Surgery, Medical University of Warsaw, Banacha 1a, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5546-9891","authenticated-orcid":false,"given":"Artur","family":"J\u00f3\u017awik","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Nutrigenomics, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Post\u0119pu 36a, Jastrz\u0119biec, 05-552 Magdalenka, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ferro, D., Baratta, F., Pastori, D., Cocomello, N., Colantoni, A., Angelico, F., and Del Ben, M. 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