{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T06:28:12Z","timestamp":1787120892930,"version":"build-2736575974"},"reference-count":42,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T00:00:00Z","timestamp":1786233600000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"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                    Food\u2010derived bioactive components play a crucial role in the prevention of cardiovascular diseases. Daidzein (DAI), a soy isoflavone, possesses notable cardioprotective potential; however, its precise role in nicotine\u2010induced atherosclerosis (AS) and its underlying mechanisms remain unclear. This study explored whether DAI protects against AS by modulating macrophage pyroptosis and lipid metabolism via redox\u2010sensitive signaling pathways. In human acute monocytic leukemia cell line (THP\u20101)\u2010derived macrophages, DAI alleviated nicotine\u2010induced pyroptosis, as evidenced by the downregulation of NOD\u2010like receptor family pyrin domain\u2010containing 3 (NLRP3), ASC, cleaved caspase\u20101, and gasdermin D (GSDMD)\u2010N, accompanied by reduced secretion of interleukin (IL)\u20101\u03b2, IL\u20106, and IL\u201018, and decreased lactate dehydrogenase (LDH) release and caspase\u20101 activity. DAI also enhanced (7\u2010nitrobenz\u20102\u2010oxa\u20101,3\u2010diazole)\u2010cholesterol (NBD)\u2010cholesterol efflux, suppressed DiI\u2010labeled oxidized low\u2010density lipoprotein (DiI\u2010ox\u2010LDL) uptake, and mitigated intracellular lipid droplet accumulation. Mechanistically, silencing nuclear factor erythroid 2\u2013related factor 2 (Nrf2), inducing reactive oxygen species (ROS), or overexpressing thioredoxin\u2010interacting protein (TXNIP) abolished the protective effects of DAI, confirming the involvement of the Nrf2\/ROS\/TXNIP pathway. In nicotine\u2010exposed apolipoprotein E\u2010deficient (apoE\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice, DAI upregulated vascular Nrf2, downregulated TXNIP and pyroptosis\u2010related proteins, improved plasma lipid profiles, alleviated systemic inflammation, and reduced aortic plaque formation, with no obvious adverse effects observed under the experimental conditions used. Collectively, DAI attenuated macrophage pyroptosis and lipid accumulation via the Nrf2\/ROS\/TXNIP pathway, thereby mitigating nicotine\u2010induced atherogenesis. These findings provide preclinical evidence for the potential of DAI as a food\u2010derived bioactive compound for smoking\u2010related AS.\n                  <\/jats:p>","DOI":"10.1002\/mnfr.70570","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T06:17:01Z","timestamp":1786342621000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Daidzein Mitigates Nicotine\u2010Induced Atherogenesis via Nrf2\/ROS\/TXNIP\u2010Dependent Inhibition of Macrophage Pyroptosis and Lipid Accumulation"],"prefix":"10.1002","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8338-1600","authenticated-orcid":false,"given":"Xiao\u2010Dan","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital of Anhui Medical University  Hefei Anhui PR 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