{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T06:28:07Z","timestamp":1787120887706,"version":"build-2736575974"},"reference-count":40,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cardiometabolic syndrome (CMS) involves interconnected dysregulation of lipid, glucose, and inflammatory pathways. Citrus peel, an agro\u2010industrial byproduct, is rich in xanthophylls with potential multitarget effects, yet their integrated mechanisms remain unclear. This study aimed to investigate the mechanistic basis and therapeutic efficacy of a citrus peel xanthophyll fraction (CPXF) in modulating the lipid\u2013glucose\u2013inflammation axis through integrated in silico and in vivo approaches. CPXF was characterized via UHPLC\u2013HRMS\/MS. Network pharmacology and molecular docking identified target interactions. In vivo validation was conducted in high\u2010fat diet plus fructose\u2010induced CMS rats, evaluating metabolic, inflammatory, oxidative, and gene expression parameters.\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010cryptoxanthin, violaxanthin, and lutein were dominant compounds. Key targets included PPARG, AMPK, SREBP1, and MMP9, with strong binding affinities (\u0394\n                    <jats:italic>G<\/jats:italic>\n                    up to \u221210.3\u00a0kcal\/mol). CPXF significantly improved glucose homeostasis, insulin resistance, lipid profile, and OGTT outcomes. It reduced TNF\u2010\n                    <jats:italic>\u03b1<\/jats:italic>\n                    , IL\u20106, and CRP, attenuated oxidative stress (\u2193MDA; \u2191SOD, CAT, GSH), and restored hepatic function. Gene expression analysis showed upregulation of Ampk and Pparg and suppression of Srebp1c. CPXF exerts synergistic, multitarget effects across the lipid\u2013glucose\u2013inflammation axis via AMPK activation, PPAR\u2010\n                    <jats:italic>\u03b3<\/jats:italic>\n                    modulation, and SREBP\u20101c suppression, supporting its potential as a food\u2010derived strategy for CMS management.\n                  <\/jats:p>","DOI":"10.1002\/mnfr.70576","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T07:06:11Z","timestamp":1785827171000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Citrus Peel Xanthophylls Orchestrate Lipid\u2013Glucose\u2013Inflammation Axis Reprogramming in Cardiometabolic Syndrome: Integrative In Silico and In Vivo Evidence"],"prefix":"10.1002","volume":"70","author":[{"given":"Muhammad Reva","family":"Aditya","sequence":"first","affiliation":[{"name":"Faculty of Medicine Universitas Brawijaya  Malang East Java Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Yusuf","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Universitas Brawijaya  Malang East Java Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanandya","family":"Kizzandy","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Universitas Brawijaya  Malang East Java Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rizki Hari","family":"Mulia","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Universitas Brawijaya  Malang East Java Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes","family":"Vianne","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Universitas Brawijaya  Malang East Java Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athaya Rahmanardi","family":"Muhammad","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Universitas Brawijaya  Malang East Java Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davina Shafa","family":"Aviantiputri","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Universitas Brawijaya  Malang East Java Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adha Fauzi","family":"Hendrawan","sequence":"additional","affiliation":[{"name":"Department of Medicine Faculty of Medicine Public Health, and Nursing Universitas Gadjah Mada  Yogyakarta Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ade Meidian","family":"Ambari","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism, and Diabetes Department of Internal Medicine Faculty of Medicine Universitas Indonesia Dr. Cipto Mangunkusumo National Referral Hospital  Jakarta Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dante Saksono","family":"Harbuwono","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Vascular Medicine Faculty of Medicine Universitas Indonesia\u2014National Cardiovascular Center Harapan Kita  Jakarta Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonello","family":"Santini","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Napoli Federico II  Napoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahrul","family":"Nurkolis","sequence":"additional","affiliation":[{"name":"State Islamic University of Sunan Kalijaga (UIN Sunan Kalijaga)  Yogyakarta Indonesia"},{"name":"Medical Research Center of Indonesia  Surabaya East Java Indonesia"},{"name":"Master of Basic Medical Science Faculty of Medicine Universitas Airlangga  Surabaya East Java Indonesia"},{"name":"Fahrul Institute for Innovation and 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