{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T12:26:47Z","timestamp":1787574407716,"version":"build-2736575974"},"reference-count":87,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Laboratory of Bioresources, Biotechnologies and Sustainable Development, Faculty of Sciences, Mohammed First University, Morocco"},{"name":"European Union\u2014Next Generation EU","award":["CN_00000033"],"award-info":[{"award-number":["CN_00000033"]}]},{"name":"European Union\u2014Next Generation EU","award":["D43C22001260001"],"award-info":[{"award-number":["D43C22001260001"]}]},{"award":["CN_00000033"],"award-info":[{"award-number":["CN_00000033"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"publisher"}]},{"award":["D43C22001260001"],"award-info":[{"award-number":["D43C22001260001"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Hyperlipidemia is a major risk factor for cardiometabolic disorders, including non-alcoholic fatty liver disease (NAFLD), and is closely associated with oxidative stress. Opuntia ficus-indica (OFI) cladodes are recognized as a rich source of bioactive phytochemicals; however, the molecular mechanisms underlying their metabolic benefits remain incompletely understood. Objectives: This study aimed to comprehensively evaluate the hypolipidemic and hepatoprotective potential of a polyphenol-rich O. ficus-indica cladode extract (OCE) using an integrated approach combining in vivo evaluation, untargeted metabolomics (UHPLC-Orbitrap-MS\/MS), molecular docking, and ADMET prediction. Methods: Hyperlipidemic mice fed a high-fat diet (HFD) were treated with OCE, while molecular docking was performed on ten major annotated phytochemicals against twelve key proteins involved in lipid metabolism and cholesterol homeostasis, including HMGCR, FAS, PPAR\u03b1, PCSK9, and NPC1L1, using simvastatin as the reference compound. Results: OCE treatment significantly improved plasma and hepatic lipid profiles, improved glucose homeostasis, and markedly reduced hepatic malondialdehyde (MDA) levels, indicating attenuation of oxidative stress. Histopathological analysis further supported a pronounced hepatoprotective effect, with a substantial reduction in hepatic steatosis. Untargeted metabolomics enabled the annotation of 102 metabolites, putatively identifying piscidic acid as the predominant phenolic constituent together with a diverse profile of flavonoids and phenolic acids. Molecular docking supported the potential contribution of these phytochemicals to the regulation of lipid metabolism through favorable interactions with multiple therapeutic targets, while ADMET prediction suggested an overall favorable pharmacokinetic and toxicity profile despite the lower intestinal permeability predicted for glycosylated derivatives. Conclusions: Overall, these findings support O. ficus-indica cladodes as a promising source of dietary bioactive compounds with potential applications in the nutritional management and prevention of hyperlipidemia and related cardiometabolic disorders.<\/jats:p>","DOI":"10.3390\/nu18172766","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:47:19Z","timestamp":1787572039000},"page":"2766","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Polyphenol-Rich Opuntia ficus-indica Cladodes: An Integrated Metabolomic, In Vivo and In Silico Study Supporting Their Hypolipidemic and Hepatoprotective Effects"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4767-1905","authenticated-orcid":false,"given":"Abderrahmane","family":"Hadini","sequence":"first","affiliation":[{"name":"Laboratory of Bioresources, Biotechnologies, and Sustainable Development, Faculty of Sciences, Mohammed First University, Oujda 60000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0786-8593","authenticated-orcid":false,"given":"Abdelhay","family":"Addous","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, Genomics, Environment and Health, Faculty of Sciences, Mohammed First University, Oujda 60000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7483-6738","authenticated-orcid":false,"given":"Abdellah","family":"Baraich","sequence":"additional","affiliation":[{"name":"Laboratory of Bioresources, Biotechnologies, and Sustainable Development, Faculty of Sciences, Mohammed First University, Oujda 60000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1741-9620","authenticated-orcid":false,"given":"Mourad","family":"Bendada","sequence":"additional","affiliation":[{"name":"Laboratory of the Improvement of Agricultural Production, Biotechnology and the Environment, Faculty of Sciences, Mohammed First University, Oujda 60000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Karim","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, Genomics, Environment and Health, Faculty of Sciences, Mohammed First University, Oujda 60000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9275-5061","authenticated-orcid":false,"given":"Mohammed","family":"Choukri","sequence":"additional","affiliation":[{"name":"Biochemistry Laboratory, Central Laboratory Service, University Hospital Center, Oujda 60000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imane","family":"Mokhtari","sequence":"additional","affiliation":[{"name":"Laboratory of Bioresources, Biotechnologies, and Sustainable Development, Faculty of Sciences, Mohammed First University, Oujda 60000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00e9my","family":"Cordazzo","sequence":"additional","affiliation":[{"name":"UMR1332 BFP, University of Bordeaux, INRAE, 33140 Villenave d\u2019Ornon, France"},{"name":"Bordeaux Metabolome, MetaboHUB, PHENOME-EMPHASIS, 33140 Villenave d\u2019Ornon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8151-7420","authenticated-orcid":false,"given":"Pierre","family":"P\u00e9triacq","sequence":"additional","affiliation":[{"name":"UMR1332 BFP, University of Bordeaux, INRAE, 33140 Villenave d\u2019Ornon, France"},{"name":"Bordeaux Metabolome, MetaboHUB, PHENOME-EMPHASIS, 33140 Villenave d\u2019Ornon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Souliman","family":"Amrani","sequence":"additional","affiliation":[{"name":"Laboratory of Bioresources, Biotechnologies, and Sustainable Development, Faculty of Sciences, Mohammed First University, Oujda 60000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1334-3072","authenticated-orcid":false,"given":"Anthony","family":"Bernard","sequence":"additional","affiliation":[{"name":"UMR1332 BFP, University of Bordeaux, INRAE, 33140 Villenave d\u2019Ornon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7577-9977","authenticated-orcid":false,"given":"Khalid El","family":"Bekkaye","sequence":"additional","affiliation":[{"name":"Laboratory of the Improvement of Agricultural Production, Biotechnology and the Environment, Faculty of Sciences, Mohammed First University, Oujda 60000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0718-5450","authenticated-orcid":false,"given":"Luca","family":"Rastrelli","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia, University of Salerno, Via Giovanni Paolo II, 132, Fisciano, 84084 Salerno, Italy"},{"name":"National Biodiversity Future Center (NBFC), 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5315-3055","authenticated-orcid":false,"given":"Maria","family":"D\u2019Elia","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia, University of Salerno, Via Giovanni Paolo II, 132, Fisciano, 84084 Salerno, Italy"},{"name":"National Biodiversity Future Center (NBFC), 90133 Palermo, Italy"},{"name":"Dipartimento di Scienze della Terra e del Mare, University of Palermo, 90123 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7492-0692","authenticated-orcid":false,"given":"Hicham","family":"Harnafi","sequence":"additional","affiliation":[{"name":"Laboratory of Bioresources, Biotechnologies, and Sustainable Development, Faculty of Sciences, Mohammed First University, Oujda 60000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s12943-025-02258-1","article-title":"Lipid Metabolic Reprograming: The Unsung Hero in Breast Cancer Progression and Tumor Microenvironment","volume":"24","author":"Wan","year":"2025","journal-title":"Mol. 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