{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T12:20:26Z","timestamp":1788524426459,"version":"build-2803163510"},"reference-count":71,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2025YFE0104100"],"award-info":[{"award-number":["2025YFE0104100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["scijournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Sci Food Agric"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Non\u2010alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide, with oxidative stress and lipid dysregulation as central pathogenic drivers. Pomegranate seed oil (PSO), rich in the conjugated fatty acid punicic acid, has demonstrated potential antioxidant and lipid\u2010modulating properties, yet its hepatoprotective mechanisms remain incompletely characterized at the metabolic level.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Gas chromatographic\u2013mass spectrometric analysis of the fatty acid composition of supercritical CO\n                      <jats:sub>2<\/jats:sub>\n                      \u2010extracted PSO revealed that punicic acid was the predominant fatty acid, comprising 74.47% of the total identified fatty acids, which collectively accounted for approximately 95% of the fatty acid profile. In palmitic acid (PA)\u2010challenged C57BL\/6 mice, PA administration significantly increased serum and hepatic lipid levels, liver function markers, oxidative stress indicators, and inflammatory cytokines. PSO intervention dose\u2010dependently ameliorated several of these abnormalities and markedly reduced hepatic lipid accumulation. Gas chromatography\u2013quadrupole time\u2010of\u2010flight mass spectrometry\u2010based serum metabolomics revealed that PSO markedly reversed PA\u2010induced metabolic disturbances, identifying 27 key differential metabolites predominantly associated with amino acid and lipid metabolism. Pathway enrichment analysis highlighted oxidative stress\u2010related pathways, including glutamate, taurine, and fatty acid metabolism. PSO significantly upregulated antioxidant metabolites (cysteine, glutamate, hypotaurine, \u03b1\u2010tocopherol) while downregulating oxidative markers (uric acid, xanthine). Complementary\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments in PA\u2010treated L02 human hepatocytes further demonstrated that PSO alleviated lipotoxicity by attenuating reactive oxygen species generation and preserving membrane integrity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>These findings demonstrate that PSO exerts hepatoprotective effects through multi\u2010target, multi\u2010pathway synergistic mechanisms, particularly via enhancing endogenous antioxidant defense systems, providing scientific evidence for PSO as a promising nutritional intervention strategy for NAFLD prevention and treatment. \u00a9 2026 Society of Chemical Industry.<\/jats:p>\n                  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