{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T01:17:43Z","timestamp":1775438263251,"version":"3.50.1"},"reference-count":86,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PNRR: \u201cHealth Extended ALliance for Innovative Therapies, Advanced Lab-research, and Integrated Approaches of Precision\u201d","award":["CUP: E63C22002080006"],"award-info":[{"award-number":["CUP: E63C22002080006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Metabolic syndrome (MetS) is a multifactorial cardiometabolic condition characterized by insulin resistance, visceral adiposity, dyslipidemia, hypertension, and chronic low-grade inflammation, collectively increasing the risk of type 2 diabetes mellitus, non-alcoholic fatty liver disease, and cardiovascular disease. Growing interest has focused on plant-derived dietary strategies capable of targeting multiple pathogenic pathways simultaneously. Opuntia ficus-indica fruits (OFIF) represent a complex food matrix containing betalains, polyphenols, carotenoids, soluble fiber, functional amino acids, vitamins, and minerals. Experimental evidence suggests that these constituents interact with key molecular networks implicated in MetS pathophysiology, including redox-sensitive pathways (NRF2), inflammatory signaling (NF-\u03baB), energy-sensing regulators (AMPK), and lipid metabolism proliferator-activated receptor alpha (PPAR-\u03b1) dependent mechanisms. Preclinical studies consistently report associations with improvements in oxidative stress, inflammatory markers, hepatic steatosis, and glucose homeostasis following OFIF supplementation. However, human evidence remains limited by small sample size, short intervention duration, and variability in compositional standardization. This narrative review adopts a systems-level perspective to integrate mechanistic, preclinical, and early clinical evidence in the context of metabolic syndrome pathophysiology, while critically addressing translational gaps, compositional variability, and current limitations in human validation.<\/jats:p>","DOI":"10.3390\/nu18071157","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:19:32Z","timestamp":1775434772000},"page":"1157","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Prickly Solution to Metabolic Syndrome: A Multitarget View on the Opuntia ficus-indica Fruit Phytocomplex"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6709-4537","authenticated-orcid":false,"given":"Cristina","family":"Russo","sequence":"first","affiliation":[{"name":"Section of Pathology, Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofia","family":"Surdo","sequence":"additional","affiliation":[{"name":"School of Osteopathy, Italian Center for the Study of Osteopathy (CSDOI), 95124 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9728-3542","authenticated-orcid":false,"given":"Maria Stella","family":"Valle","sequence":"additional","affiliation":[{"name":"Laboratory of Neuro-Biomechanics, Section of Physiology, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5171-7963","authenticated-orcid":false,"given":"Lucia","family":"Malaguarnera","sequence":"additional","affiliation":[{"name":"Section of Pathology, Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hamooya, B.M., Siame, L., Muchaili, L., Masenga, S.K., and Kirabo, A. (2025). Metabolic syndrome: Epidemiology, mechanisms, and current therapeutic approaches. Front. Nutr., 12.","DOI":"10.3389\/fnut.2025.1661603"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Saeedi, P., Petersohn, I., Salpea, P., Malanda, B., Karuranga, S., Unwin, N., Colagiuri, S., Guariguata, L., Motala, A.A., and Ogurtsova, K. (2019). Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res. Clin. Pract., 157.","DOI":"10.1016\/j.diabres.2019.107843"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Fahed, G., Aoun, L., Bou Zerdan, M., Allam, S., Bouferraa, Y., and Assi, H.I. (2022). Metabolic syndrome: Updates on pathophysiology and management in 2021. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23020786"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Choi, W., Woo, G.H., Kwon, T.H., and Jeon, J.H. (2025). Obesity-driven metabolic disorders: The interplay of inflammation and mitochondrial dysfunction. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26199715"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Gao, W., Guo, L., Yang, Y., Wang, Y., Xia, S., Gong, H., Zhang, B.K., and Yan, M. (2022). Dissecting the crosstalk between Nrf2 and NF-\u03baB response pathways in drug-induced toxicity. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.809952"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Di Majo, D., Ricciardi, N., Di Liberto, V., Allegra, M., Frinchi, M., Urone, G., Scordino, M., Massaro, A., Mud\u00f2, G., and Ferraro, G. (2024). The remarkable impact of Opuntia ficus-indica fruit administration on metabolic syndrome: Correlations between cognitive functions, oxidative stress and lipid dysmetabolism in the high-fat diet-fed rat model. Biomed. Pharmacother., 177.","DOI":"10.1016\/j.biopha.2024.117028"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3457","DOI":"10.2174\/1381612825666191010171819","article-title":"Nopal (Opuntia spp.) and its effects on metabolic syndrome: New insights for the use of a millenary plant","volume":"25","author":"Valverde","year":"2019","journal-title":"Curr. Pharm. Des."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1038\/s42255-019-0145-5","article-title":"Inter-organ cross-talk in metabolic syndrome","volume":"1","author":"Priest","year":"2019","journal-title":"Nat. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Abdul-Ghani, M.A., and DeFronzo, R.A. (2010). Pathogenesis of insulin resistance in skeletal muscle. J. Biomed. Biotechnol., 2010.","DOI":"10.1155\/2010\/476279"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Zatterale, F., Longo, M., Naderi, J., Raciti, G.A., Desiderio, A., Miele, C., and Beguinot, F. (2020). Chronic adipose tissue inflammation linking obesity to insulin resistance and type 2 diabetes. Front. Physiol., 10.","DOI":"10.3389\/fphys.2019.01607"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1172\/JCI29881","article-title":"Obesity induces a phenotypic switch in adipose tissue macrophage polarization","volume":"117","author":"Lumeng","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Valle, M.S., Russo, C., Surdo, S., Cambria, M.T., Campanella, M., Tuttobene, M., and Malaguarnera, L. (2025). Pathophysiological role of vitamin D deficiency in Down syndrome: Insights into metabolic dysfunction and sarcopenia. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262110756"},{"key":"ref_13","first-page":"407","article-title":"Regulation of insulin sensitivity by serine\/threonine phosphorylation of insulin receptor substrate proteins","volume":"122","author":"Copps","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/s41423-025-01284-9","article-title":"Updated insights into the molecular networks for NLRP3 inflammasome activation","volume":"22","author":"Paik","year":"2025","journal-title":"Cell. Mol. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1172\/JCI77812","article-title":"The pathogenesis of insulin resistance: Integrating signaling pathways and substrate flux","volume":"126","author":"Samuel","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.jcmgh.2018.10.016","article-title":"Resolving the paradox of hepatic insulin resistance","volume":"7","author":"Santoleri","year":"2019","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1007\/s13679-022-00473-1","article-title":"Hepatocyte mitochondrial dynamics and bioenergetics in obesity-related non-alcoholic fatty liver disease","volume":"11","author":"Legaki","year":"2022","journal-title":"Curr. Obes. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1631\/jzus.B2400053","article-title":"Roles of the Keap1\/Nrf2 pathway and mitophagy in liver diseases","volume":"26","author":"Zhou","year":"2025","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Garcia-Llorens, G., El Ouardi, M., and Valls-Belles, V. (2025). Oxidative stress fundamentals: Unraveling the pathophysiological role of redox imbalance in non-communicable diseases. Appl. Sci., 15.","DOI":"10.3390\/app151810191"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Xia, Y., Zhai, X., Qiu, Y., Lu, X., and Jiao, Y. (2022). The Nrf2 in obesity: A friend or foe?. Antioxidants, 11.","DOI":"10.3390\/antiox11102067"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8061","DOI":"10.2147\/JIR.S490418","article-title":"The NRF-2\/HO-1 signaling pathway: A promising therapeutic target for metabolic dysfunction-associated steatotic liver disease","volume":"17","author":"Li","year":"2024","journal-title":"J. Inflamm. Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Park, J.S., Rustamov, N., and Roh, Y.S. (2023). The roles of NRF2-regulated oxidative stress and mitochondrial quality control in chronic liver diseases. Antioxidants, 12.","DOI":"10.3390\/antiox12111928"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/j.cell.2012.02.017","article-title":"Mechanisms for insulin resistance: Common threads and missing links","volume":"148","author":"Samuel","year":"2012","journal-title":"Cell"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Li, N., Li, X., Ding, Y., Liu, X., Diggle, K., Kisseleva, T., and Brenner, D.A. (2023). SREBP regulation of lipid metabolism in liver disease, and therapeutic strategies. Biomedicines, 11.","DOI":"10.20944\/preprints202310.2022.v1"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lipke, K., Kubis-Kubiak, A., and Piwowar, A. (2022). Molecular mechanism of lipotoxicity as an interesting aspect in the development of pathological states\u2014Current view of knowledge. Cells, 11.","DOI":"10.3390\/cells11050844"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1038\/s41577-024-01103-8","article-title":"Adipokines: Masterminds of metabolic inflammation","volume":"25","author":"Tilg","year":"2025","journal-title":"Nat. Rev. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1053\/j.gastro.2019.12.054","article-title":"Adipose tissue-liver cross talk in the control of whole-body metabolism: Implications in nonalcoholic fatty liver disease","volume":"158","author":"Azzu","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.2337\/db06-1491","article-title":"Metabolic endotoxemia initiates obesity and insulin resistance","volume":"56","author":"Cani","year":"2007","journal-title":"Diabetes"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1136\/gutjnl-2020-323071","article-title":"Gut microbiota-derived metabolites as central regulators in metabolic disorders","volume":"70","author":"Agus","year":"2021","journal-title":"Gut"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"De C\u00f3l, J.P., de Lima, E.P., Pompeu, F.M., Cressoni Ara\u00fajo, A., de Alvares Goulart, R., Bechara, M.D., Laurindo, L.F., M\u00e9ndez-S\u00e1nchez, N., and Barbalho, S.M. (2024). Underlying mechanisms behind the brain\u2013gut\u2013liver axis and metabolic-associated fatty liver disease (MAFLD): An update. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25073694"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"14879","DOI":"10.3390\/molecules190914879","article-title":"Nopal cactus (Opuntia ficus-indica) as a source of bioactive compounds for nutrition, health and disease","volume":"19","author":"Badreddine","year":"2014","journal-title":"Molecules"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Giraldo-Silva, L., Ferreira, B., Rosa, E., and Dias, A.C.P. (2023). Opuntia ficus-indica fruit: A systematic review of its phytochemicals and pharmacological activities. Plants, 12.","DOI":"10.3390\/plants12030543"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"851","DOI":"10.3109\/09637486.2015.1095862","article-title":"Cladodes from prickly pear as a functional ingredient: Effect on fat retention, oxidative stability, nutritional and sensory properties of cookies","volume":"66","author":"Msaddak","year":"2015","journal-title":"Int. J. Food Sci. Nutr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.foodres.2018.03.062","article-title":"Phytochemical characterization of different prickly pear (Opuntia ficus-indica (L.) Mill.) cultivars and botanical parts: UHPLC-ESI-MSn metabolomics profiles and their chemometric analysis","volume":"108","author":"Mena","year":"2018","journal-title":"Food Res. Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1021\/jf048751y","article-title":"Color, betalain pattern, and antioxidant properties of cactus pear (Opuntia spp.) clones","volume":"53","author":"Stintzing","year":"2005","journal-title":"J. Agric. Food Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7851","DOI":"10.1021\/jf050636f","article-title":"Biothiols, taurine, and lipid-soluble antioxidants in the edible pulp of Sicilian cactus pear (Opuntia ficus-indica) fruits and changes of bioactive juice components upon industrial processing","volume":"53","author":"Tesoriere","year":"2005","journal-title":"J. Agric. Food Chem."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Shoukat, R., Cappai, M., Pia, G., and Pilia, L. (2023). An updated review: Opuntia ficus indica (OFI) chemistry and its diverse applications. Appl. Sci., 13.","DOI":"10.3390\/app13137724"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Abdnim, R., Lafdil, F.Z., Elrherabi, A., El Fadili, M., Kandsi, F., Benayad, O., Legssyer, A., Ziyyat, A., Mekhfi, H., and Bnouham, M. (2024). Fatty acids characterisation by GC-MS, antiglycation effect and protection of erythrocytes from oxidative damage induced by glycation of albumin of Opuntia ficus-indica (L.) Mill seed oil. J. Ethnopharmacol., 329.","DOI":"10.1016\/j.jep.2024.118106"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Ramadan, M.F., Ayoub, T.E.M., and Rohn, S. (2021). Opuntia ficus-indica (L.) Mill. Bioactive ingredients and phyto-constituents. Opuntia spp.: Chemistry, Bioactivity and Industrial Applications, Springer.","DOI":"10.1007\/978-3-030-78444-7"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3831\/KPI.2022.25.2.121","article-title":"Chemical composition of cactus pear seed oil: Phenolics identification and antioxidant activity","volume":"25","author":"Ali","year":"2022","journal-title":"J. Pharmacopunct."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Stachelska, M.A., Karpi\u0144ski, P., and Kruszewski, B. (2025). A comprehensive review of biological properties of flavonoids and their role in the prevention of metabolic, cancer and neurodegenerative diseases. Appl. Sci., 15.","DOI":"10.3390\/app151910840"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Jomova, K., Alomar, S.Y., Valko, R., Liska, J., Nepovimova, E., Kuca, K., and Valko, M. (2025). Flavonoids and their role in oxidative stress, inflammation, and human diseases. Chem. Biol. Interact., 413.","DOI":"10.1016\/j.cbi.2025.111489"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Russo, C., Valle, M.S., D\u2019Angeli, F., Surdo, S., Giunta, S., Barbera, A.C., and Malaguarnera, L. (2024). Beneficial effects of Manilkara zapota-derived bioactive compounds in the epigenetic program of neurodevelopment. Nutrients, 16.","DOI":"10.3390\/nu16142225"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1093\/ajcn\/80.2.391","article-title":"Supplementation with cactus pear (Opuntia ficus-indica) fruit decreases oxidative stress in healthy humans: A comparative study with vitamin C","volume":"80","author":"Tesoriere","year":"2004","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Russo, B., Picconi, F., Malandrucco, I., and Frontoni, S. (2019). Flavonoids and insulin-resistance: From molecular evidences to clinical trials. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20092061"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1089\/jmf.2017.4052","article-title":"Quercetin-induced AMP-activated protein kinase activation attenuates vasoconstriction through LKB1\u2013AMPK signaling pathway","volume":"21","author":"Kim","year":"2018","journal-title":"J. Med. Food"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Qin, Y., Niu, K., Zeng, Y., Liu, P., Yi, L., Zhang, T., Zhang, Q.Y., Zhu, J.D., and Mi, M.T. (2013). Isoflavones for hypercholesterolaemia in adults. Cochrane Database Syst. Rev., 2013.","DOI":"10.1002\/14651858.CD009518.pub2"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Hu, H., Weng, J., Cui, C., Tang, F., Yu, M., Zhou, Y., Shao, F., and Zhu, Y. (2022). The hypolipidemic effect of hawthorn leaf flavonoids through modulating lipid metabolism and gut microbiota in hyperlipidemic rats. Evid. Based Complement. Alternat. Med., 2022.","DOI":"10.1155\/2022\/3033311"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Daza, M.C., and de Vos, W.M. (2022). Polyphenols as drivers of a homeostatic gut microecology and immuno-metabolic traits of Akkermansia muciniphila. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010045"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"544","DOI":"10.3934\/microbiol.2022035","article-title":"Impact of grape polyphenols on Akkermansia muciniphila and the gut barrier","volume":"8","author":"Mezhibovsky","year":"2022","journal-title":"AIMS Microbiol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Mena, A., Ochoa-Mart\u00ednez, L.A., Gonz\u00e1lez-Herrera, S.M., Rutiaga-Qui\u00f1ones, O.M., Gonz\u00e1lez-Laredo, R.F., and Olmedilla-Alonso, B. (2023). Natural pigments of plant origin: Classification, extraction and application in foods. Food Chem., 398.","DOI":"10.1016\/j.foodchem.2022.133908"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Attanzio, A., Restivo, I., Tutone, M., Tesoriere, L., Allegra, M., and Livrea, M.A. (2022). Redox properties, bioactivity and health effects of indicaxanthin. Antioxidants, 11.","DOI":"10.3390\/antiox11122364"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.ejmech.2019.07.006","article-title":"Indicaxanthin, a multi-target natural compound from Opuntia ficus-indica fruit","volume":"179","author":"Allegra","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1017\/S0007114513002663","article-title":"Indicaxanthin inhibits NOX-1 activation and NF-\u03baB-dependent inflammatory mediators","volume":"111","author":"Tesoriere","year":"2014","journal-title":"Br. J. Nutr."},{"key":"ref_55","first-page":"2138","article-title":"Betanin induces Nrf2-mediated expression of detoxifying\/antioxidant enzymes","volume":"110","author":"Paluszczak","year":"2013","journal-title":"Br. J. Nutr."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Terzo, S., Attanzio, A., Calvi, P., Mul\u00e8, F., Tesoriere, L., Allegra, M., and Amato, A. (2021). Indicaxanthin from Opuntia ficus-indica fruit ameliorates glucose dysmetabolism in HFD-fed mice. Antioxidants, 11.","DOI":"10.3390\/antiox11010080"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"da Silva, D.V.T., Pereira, A.D., Boaventura, G.T., Ribeiro, R.S.A., Ver\u00edcimo, M.A., Carvalho-Pinto, C.E., Bai\u00e3o, D.D.S., Del Aguila, E.M., and Paschoalin, V.M.F. (2019). Short-term betanin intake reduces oxidative stress in Wistar rats. Nutrients, 11.","DOI":"10.3390\/nu11091978"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1196\/annals.1322.057","article-title":"Antioxidant betalains from cactus pear inhibit endothelial ICAM-1 expression","volume":"1028","author":"Gentile","year":"2004","journal-title":"Ann. New York Acad. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.2337\/db14-1916","article-title":"Dietary polyphenols promote growth of Akkermansia muciniphila and attenuate HFD-induced metabolic syndrome","volume":"64","author":"Roopchand","year":"2015","journal-title":"Diabetes"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Shaheen, N., Khursheed, W., Gurung, B., and Wang, S. (2025). Akkermansia muciniphila: A key player in gut microbiota-based disease modulation. Microbiol. Res., 301.","DOI":"10.1016\/j.micres.2025.128317"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"384S","DOI":"10.3945\/an.112.003517","article-title":"Health-promoting components of fruits and vegetables in the diet","volume":"4","author":"Liu","year":"2013","journal-title":"Adv. Nutr."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Tan, B.L., and Norhaizan, M.E. (2019). Carotenoids: How effective are they to prevent age-related diseases?. Molecules, 24.","DOI":"10.3390\/molecules24091801"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1017\/S0007114515001622","article-title":"Carotenoid consumption is related to lower lipid oxidation and DNA damage in middle-aged men","volume":"114","author":"Cocate","year":"2015","journal-title":"Br. J. Nutr."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3649","DOI":"10.1016\/j.febslet.2009.10.045","article-title":"Luteolin suppresses adipocyte-dependent activation of macrophages by inhibiting JNK activation","volume":"583","author":"Ando","year":"2009","journal-title":"FEBS Lett."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Murillo, A.G., Hu, S., and Fernandez, M.L. (2019). Zeaxanthin: Metabolism, properties, and antioxidant protection. Antioxidants, 8.","DOI":"10.3390\/antiox8090390"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1017\/S0029665118002641","article-title":"\u03b2-Carotene in the human body: Metabolic bioactivation pathways","volume":"78","author":"Bohn","year":"2019","journal-title":"Proc. Nutr. Soc."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Balbuena, E., Cheng, J., and Eroglu, A. (2022). Carotenoids in orange carrots mitigate non-alcoholic fatty liver disease progression. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.987103"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.cell.2014.03.012","article-title":"Nuclear receptors, RXR, and the big bang","volume":"157","author":"Evans","year":"2014","journal-title":"Cell"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1093\/ajcn\/69.6.1086","article-title":"Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans","volume":"69","author":"Carr","year":"1999","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.freeradbiomed.2007.03.024","article-title":"Vitamin E, antioxidant and nothing more","volume":"43","author":"Traber","year":"2007","journal-title":"Free Radic. Biol. Med."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Jin, S., and Kang, P.M. (2024). A systematic review on advances in management of oxidative stress-associated cardiovascular diseases. Antioxidants, 13.","DOI":"10.3390\/antiox13080923"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"37","DOI":"10.7326\/0003-4819-142-1-200501040-00110","article-title":"Meta-analysis: High-dosage vitamin E supplementation may increase all-cause mortality","volume":"142","author":"Miller","year":"2005","journal-title":"Ann. Intern. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1543S","DOI":"10.3945\/ajcn.2009.26736B","article-title":"Food synergy: An operational concept for understanding nutrition","volume":"89","author":"Jacobs","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Silva, M.A., Albuquerque, T.G., Pereira, P., Ramalho, R., Vicente, F., Oliveira, M.B.P.P., and Costa, H.S. (2021). Opuntia ficus-indica (L.) Mill.: A multi-benefit potential to be exploited. Molecules, 26.","DOI":"10.3390\/molecules26040951"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.4239\/wjd.v6.i10.1152","article-title":"Magnesium and type 2 diabetes","volume":"6","author":"Barbagallo","year":"2015","journal-title":"World J. Diabetes"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1038\/ejcn.2016.154","article-title":"Effect of magnesium supplementation on glucose metabolism","volume":"70","author":"Veronese","year":"2016","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Veronese, N., Pizzol, D., Smith, L., Dominguez, L.J., and Barbagallo, M. (2022). Effect of magnesium supplementation on inflammatory parameters. Nutrients, 14.","DOI":"10.3390\/nu14030679"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Aburto, N.J., Hanson, S., Gutierrez, H., Hooper, L., Elliott, P., and Cappuccio, F.P. (2013). Effect of increased potassium intake on cardiovascular risk factors and disease: Systematic review and meta-analyses. BMJ, 346.","DOI":"10.1136\/bmj.f1378"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Filippini, T., Naska, A., Kasdagli, M.I., Torres, D., Lopes, C., Carvalho, C., Moreira, P., Malavolti, M., Orsini, N., and Whelton, P.K. (2020). Potassium intake and blood pressure: A dose-response meta-analysis of randomized controlled trials. J. Am. Heart Assoc., 9.","DOI":"10.1161\/JAHA.119.015719"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3746\/pnf.2017.22.1.1","article-title":"Zinc in pancreatic islet biology, insulin sensitivity, and diabetes","volume":"22","author":"Maret","year":"2017","journal-title":"Prev. Nutr. Food Sci."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Klec, C., Ziomek, G., Pichler, M., Malli, R., and Graier, W.F. (2019). Calcium signaling in \u00df-cell physiology and pathology: A revisit. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20246110"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Wang, L., Xie, Z., Wu, M., Chen, Y., Wang, X., Li, X., and Liu, F. (2024). The role of taurine through endoplasmic reticulum in physiology and pathology. Biochem. Pharmacol., 226.","DOI":"10.1016\/j.bcp.2024.116386"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/978-3-030-74180-8_10","article-title":"Role of L-arginine in nitric oxide synthesis and health in humans","volume":"1332","author":"Wu","year":"2021","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Guan, Z.-W., Yu, E.-Z., and Feng, Q. (2021). Soluble dietary fiber, one of the most important nutrients for the gut microbiota. Molecules, 26.","DOI":"10.3390\/molecules26226802"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/s41579-025-01183-w","article-title":"Gut microbiota-derived short-chain fatty acids and their role in human health and disease","volume":"23","author":"Mukhopadhya","year":"2025","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Torres, I., Castrej\u00f3n-T\u00e9llez, V., Soto, M.E., Rubio-Ruiz, M.E., Manzano-Pech, L., and Guarner-Lans, V. (2021). Oxidative stress, plant natural antioxidants, and obesity. Int. J. Mol. 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