Molecular Nutrition & Food Research最新文献

{"title":"Dietary Titanium Dioxide (E171) Alters the Colon Transcriptome—Evidence From a Human Dietary Intervention Study","authors":"Nicolaj S. Bischoff,&nbsp;Anna K. Undas,&nbsp;Greet van Bemmel,&nbsp;Marcel van Herwijnen,&nbsp;Marcha Verheijen,&nbsp;Simone G. Van Breda,&nbsp;Jacco J. Briedé,&nbsp;Lana Drenth-Brink,&nbsp;Marcella Peelen-Buijs,&nbsp;Iris Elferink,&nbsp;Héloïse Proquin,&nbsp;Henk van Loveren,&nbsp;Ad A. van Bodegraven,&nbsp;Dick T. H. M. Sijm,&nbsp;Theo M. de Kok","doi":"10.1002/mnfr.70583","DOIUrl":"10.1002/mnfr.70583","url":null,"abstract":"<p>Food-grade titanium dioxide (E171) has been removed from the European food market due to concerns about its potential genotoxicity, yet human evidence remains limited. Given its continuous use outside the European Union, clarifying its potential hazard is essential for human risk assessment. In a randomized crossover study, 31 adults consumed 2 mg/kg body weight/day of E171 for 2 weeks, with biospecimens collected after both control and exposure periods. Oral intake resulted in elevated titanium concentrations in feces (CTRL: 6.3 mg/kg; E171: 377 mg/kg). Particle characterization showed a median size of 228 nm, with 9% &lt;100 nm. Systemic oxidative stress increased, evidenced by increased superoxide radical levels in whole blood (<i>p</i> = 0.057). Transcriptomic profiling of colon biopsies revealed activation of 73 pathways linked to oxidative stress, cellular metabolism, and colorectal cancer-associated processes. The observed transcriptional changes were consistent with findings of its proposed mode of action. This human intervention study characterizes the effects of dietary E171 following human gastrointestinal digestion and provides evidence that exposure to dietary E171 induces systemic oxidative stress and transcriptional changes in the colon. These findings strengthen regulatory concerns about E171 as a food additive and its potentially harmful effects on human gastrointestinal health.</p>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"70 16","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mnfr.70583","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148768606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Hidden Burden of Water-Binding Additives in Meat Products: Biochemical, Clinical, and Psychosocial Implications","authors":"Oleksandr Kamyshnyi,&nbsp;Iryna Halabitska,&nbsp;Magnar Bjorås,&nbsp;Ingrid Bjørnes Sæther,&nbsp;Trygve Brautaset,&nbsp;Iryna Kamyshna,&nbsp;Oleh Lushchak,&nbsp;Valentyn Oksenych,&nbsp;Pavlo Petakh,&nbsp;Denis E. Kainov","doi":"10.1002/mnfr.70591","DOIUrl":"10.1002/mnfr.70591","url":null,"abstract":"<p>Processed meat products are widely consumed worldwide, especially because they are affordable and easy to prepare. Their production often involves the use of water-binding additives such as phosphates, nitrites, and sodium chloride. Although these substances improve taste, texture, and shelf life, their potential effects on human health remain unclear. This review aims to summarize current knowledge about the possible biological and clinical effects of these additives. Injection (brining) technology is commonly used to increase product weight and improve quality. However, it may also lead to regular consumption of these additives. Phosphates may influence mineral balance and could be linked to changes in vitamin D metabolism and vascular health. Nitrites can participate in the formation of N-nitroso compounds, which have been shown to have harmful effects in experimental studies. High sodium intake is associated with increased blood pressure and cardiovascular risk. Some studies also suggest that these additives may affect the gut microbiota and promote low-grade inflammation. Certain groups, including people with chronic diseases, may be more sensitive to these effects. Cultivated meat has been proposed as a potential alternative that may reduce reliance on such additives; however, it often still requires similar ingredients to achieve desired texture and stability, and its potential health benefits remain uncertain. Current regulations in the United States and the European Union primarily focus on individual additives and do not fully account for total daily intake from different foods. In addition, food labels often do not provide detailed quantitative information. Further research is needed to better understand long-term effects and combined exposure.</p>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"70 16","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mnfr.70591","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148768607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary Vitamin D2 Is Less Potent Than Vitamin D3 at Maintaining or Restoring Structure and Metabolism of Skeletal Muscle and Heart in Male Rats","authors":"Soumam Dutta,&nbsp;Athira Anilkumar S,&nbsp;Mohd Urooj,&nbsp;Ayesha Ismail","doi":"10.1002/mnfr.70588","DOIUrl":"10.1002/mnfr.70588","url":null,"abstract":"<div>\u0000 \u0000 <p>Vitamin D (VD) deficiency is prevalent globally. To improve dietary recommendations for food fortification, we used male rats fed with diets depleted of VD or supplemented/rehabilitated with either vitamin D2 or vitamin D3 or combination, and compared their impact on calcium homeostasis, skeletal muscle and heart. Body composition was assessed by DEXA, muscle strength by grip test. Serum calcium, parathyroid hormone and 25-hydroxyvitamin D [25(OH)D] were measured using standard methods. Skeletal muscle and left ventricle were used for histopathology; RNA and protein were extracted for analysis of gene expression and enzymatic activity, respectively. 25-hydroxylated form of D3 was significantly higher than that of D2 in serum. D2 was less efficacious than D3 at improving skeletal muscle fiber size, strength, expression of contractility genes [<i>Myh2, Tnnc1</i>] and metabolic enzymes [<i>Cs, β-Had</i>]. Under maintenance cardiac contractility gene expression [<i>Myh7 &amp; Serca2a</i>] was comparable between the D2 and D3 groups, though 400 IU D2 notably suppressed <i>Serca2</i> expression. Post-rehabilitation, the 2000 IU D3 group demonstrated significant improvement in these genes. Overall, our study demonstrates similar efficacy of D2 and D3 at regulating calcium homeostasis, but a better efficacy of D3 than D2 on structure, function and energy metabolism of skeletal muscle and heart.</p>\u0000 </div>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"70 16","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148768828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Berberine's Role in Modulating Gut Microbiota and Endocannabinoid System in Colitis-Associated Colorectal Cancer","authors":"Yalan Huang,&nbsp;Junhui Zhang,&nbsp;Huiqing Yu,&nbsp;Hong Yang,&nbsp;Mengting Chen","doi":"10.1002/mnfr.70585","DOIUrl":"10.1002/mnfr.70585","url":null,"abstract":"<div>\u0000 \u0000 <p>Colorectal cancer (CRC) linked to colitis is a major cause of cancer-related deaths, highlighting the need for effective treatment options. This study aimed to investigate the effects of berberine (BRR) on gut microbiota and the endocannabinoid system (ECS) in a mouse model of colitis-associated CRC, which was induced using azoxymethane (AOM) and dextran sulfate sodium (DSS). Through a combination of animal experiments, microbial sequencing, and biochemical assays, we discovered that BRR significantly inhibited tumor development. This was demonstrated by a dose-dependent increase in body weight and a notable decrease in both the number and size of tumors. Histopathological examinations showed a reduction in aberrant crypt foci and inflammation. Additionally, BRR treatment led to lower levels of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6, while increasing the levels of the anti-inflammatory cytokine IL-10, indicating a modulation of immune responses. Importantly, BRR altered gut microbial communities by promoting beneficial bacteria such as <i>Akkermansia muciniphila</i>, <i>Bacteroides</i>, <i>Lachnoclostridium</i>, <i>Blautia</i>, and <i>Prevotellaceae_UCG-001</i>, while reducing harmful species. We also observed improvements in intestinal barrier integrity, characterized by decreased permeability and lower levels of plasma lipopolysaccharides. Furthermore, BRR restored the expression of cannabinoid receptors CB2 and GPR55, suggesting that the ECS plays a role in mediating its effects. In summary, BRR shows significant promise in alleviating colitis-associated CRC through various mechanisms, including the modulation of gut microbiota, regulation of immune responses, and enhancement of intestinal barrier function. Future studies should aim to validate these findings clinically and further explore the efficacy of BRR in the prevention and treatment of CRC.</p>\u0000 </div>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"70 16","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148768604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ketogenic Diet: A Metabolic Key to Overcoming Cancer Therapy Resistance","authors":"Seerwan Hamadameen Sulaiman,&nbsp;Rebaz Anwar Omer,&nbsp;Khalamala Ibrahim Salih Barzani,&nbsp;Zanco Hassan Jawhar,&nbsp;Hemn A.H. Barzani","doi":"10.1002/mnfr.70578","DOIUrl":"10.1002/mnfr.70578","url":null,"abstract":"<div>\u0000 \u0000 <p>The ketogenic diet (KD), characterized by very low carbohydrate intake, moderate protein consumption, and variable fat content depending on the specific dietary protocol, has emerged as a promising metabolic approach in oncology. Although significant progress has been achieved in chemotherapy and immunotherapy for cancer treatment, it still faces challenges in terms of resistance to drugs, systemic toxicity, and immunosuppressive microenvironments of tumor tissues. The KD has been reported to exploit the metabolic weaknesses of tumor cells, such as glycolytic addiction and mitochondrial rigidity, while sparing normal tissue metabolism. The anticancer effects of KD are linked to metabolic and signaling reprogramming that may increase tumor sensitivity to treatment. The ketone bodies, especially β-hydroxybutyrate, play a significant role in tumor metabolism and stress response through histone deacetylase inhibition, anti-inflammatory properties in normal tissues, and modulation of chemotherapy-induced toxicity. A large body of preclinical data supports the use of KD to enhance the efficacy of chemotherapeutic agents, such as cisplatin, doxorubicin, temozolomide, and gemcitabine, through mechanisms that include redox imbalance, inhibition of DNA repair, and induction of apoptosis in tumor cells. Emerging experimental data also indicate that KD may affect the tumor immune microenvironment by modulating effector and suppressive immune cells and by interacting with immune checkpoint therapy. However, the translation of these data into the clinic is heterogeneous. Early-phase clinical trials and feasibility studies in glioblastoma, breast, colorectal, and pancreatic cancers have shown that KD is feasible in the clinic and that some benefits in metabolic parameters and quality of life are observed, but evidence of anticancer activity remains limited. Importantly, the response to KD in the clinic seems to depend on the formulation and implementation of the dietary intervention, including the use of high-fat KDs versus very-low-calorie ketogenic diets (VLCKDs), as well as the metabolic context in which the intervention is performed, including obesity and insulin resistance. Overall, current data support KD as a biologically plausible and hypothesis-generating immunometabolic strategy that warrants further evaluation in well-designed, controlled clinical trials with careful attention to dietary composition, metabolic phenotype, safety, and patient adherence.</p>\u0000 </div>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"70 16","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148768605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Neurodegeneration With Naringenin: Mechanistic Perspectives and Therapeutic Implications","authors":"Nista Gurung,&nbsp;Ganesh Bohara,&nbsp;Nikesh Rimal,&nbsp;Dong-Young Choi","doi":"10.1002/mnfr.70584","DOIUrl":"10.1002/mnfr.70584","url":null,"abstract":"<div>\u0000 \u0000 <p>Neurological diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, retinal neurodegeneration, and spinal cord injury represent a growing global health burden with limited therapeutic options. Natural compounds, particularly flavonoids, have emerged as promising neuroprotective agents. Naringenin (NAR), a citrus-derived flavanone, exhibits potent antioxidant, anti-inflammatory, and neuroprotective properties. Recent studies revealed that NAR modulates multiple cellular pathways, including oxidative stress reduction, mitochondrial protection, autophagy induction, inhibition of microglial activation, and suppression of neuroinflammatory signaling such as NF-κB and NLRP3 inflammasome. Furthermore, NAR has demonstrated the ability to reduce amyloid-β plaque deposition, inhibit α-synuclein aggregation, preserve dopaminergic neurons, modulate immune responses in multiple sclerosis, and improve functional recovery after spinal cord injury. This review comprehensively summarizes the mechanistic insights and therapeutic potential of NAR across various neurodegenerative diseases, highlighting its promise as a multifunctional neuroprotective agent and the need for further translational research.</p>\u0000 </div>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"70 16","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148768610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pear Polysaccharide Alleviates Asthma Symptoms in Association With a Ferroptosis-Related Biomarker Network: An Integrated Bioinformatics and Experimental Study","authors":"Fei Yang,&nbsp;Qiongling Mao,&nbsp;Jinlong Liu,&nbsp;Hailiqian Taoerdahong","doi":"10.1002/mnfr.70574","DOIUrl":"10.1002/mnfr.70574","url":null,"abstract":"<div>\u0000 \u0000 <p>Asthma remains a prevalent global health challenge, necessitating novel therapeutic targets. This study hypothesized that pear polysaccharide alleviates asthma by modulating ferroptosis-related biomarkers. We integrated transcriptomic data (GSE143303, GSE147878) with database mining (CTD, OMIM, GeneCards, HERB, and FerrDb) to identify genes shared among asthma, pear, and ferroptosis. Machine learning screened core biomarkers, validated in independent datasets (GSE43696 and GSE63142). An ovalbumin-induced asthma mouse model was used to test the effect of Korla fragrant pear polysaccharide (10 and 40 mg/kg). Bioinformatics analysis identified 146 asthma-pear shared genes enriched in oxidative stress. Seven biomarkers (AR, CDKN1A, HMOX1, IL1B, IL6, PARP1, and TP53) were screened. In vivo, pear polysaccharide significantly attenuated cytokine release, and reversed the expression of the seven biomarkers in lung tissue and BALF of murine asthma model.Our study demonstrates that pear polysaccharide alleviates asthma pathology, potentially by targeting a hub gene network centered on ferroptosis-related biomarkers.</p>\u0000 </div>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"70 16","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148768661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Epigallocatechin Gallate Supplementation on Inflammation, Iron Status, and Metabolomic Profiles in Women With Obesity: A Pilot Randomized Controlled Trial","authors":"Sixtus Aguree,&nbsp;Kedir N. Turi,&nbsp;Alexandra R. Handt,&nbsp;Marian Kohut,&nbsp;Manju B. Reddy","doi":"10.1002/mnfr.70575","DOIUrl":"10.1002/mnfr.70575","url":null,"abstract":"<p>Obesity in women of reproductive age is often associated with low-grade inflammation and functional iron deficiency. Epigallocatechin gallate (EGCG), a major green tea catechin, has antioxidant, anti-inflammatory, and metabolic-regulating properties but may also interfere with iron absorption. This randomized, double-blind, placebo-controlled pilot study evaluated the effects of EGCG on lipid profile, inflammation, iron status, and plasma metabolomics in women with obesity. Seventeen participants (BMI ≥30 kg/m²; age 20–44 years) received 400 mg/day EGCG (green tea extract: 98% polyphenols, 60% catechins, ∼50% EGCG) or placebo for eight weeks. Outcomes included serum lipids, inflammatory markers (CRP, IL-6, TNF-α, IL-10), iron indices (ferritin, hepcidin, serum iron, transferrin saturation), glucose, and metabolomics. No between-group difference remained significant after correction for multiple comparisons. Total cholesterol (β = −10.9 mg/dL; <i>p</i>  = 0.16) and LDL-C (β = −9.7 mg/dL; <i>p</i>  = 0.16) showed decreases, and IL-6 the largest, though nonsignificant, reduction (<i>p</i>  = 0.09); other cytokines and glucose were unchanged. Metabolomics identified 29 nominally differential metabolites enriched in lipid metabolism, plasmalogen biosynthesis, and mitochondrial β-oxidation, none surviving FDR correction. Iron status was stable. These findings suggest metabolic effects of EGCG and support short-term safety at 400 mg/day. Larger, longer trials with targeted metabolomics are warranted.</p>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"70 16","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mnfr.70575","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148768663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Dietary Protein Source Modulates Obesity Development and Induces Distinct Plasma Lipid Profiles and Transcriptome Profiles in Liver and Adipose Tissue","authors":"Lene S. Myrmel,&nbsp;Even Fjære,&nbsp;Annette Bernhard,&nbsp;Josef D. Rasinger,&nbsp;Ole Jakob Nøstbakken,&nbsp;Helene Søiland,&nbsp;Philipp Rausch,&nbsp;Martin von Bergen,&nbsp;Ulrike Rolle-Kampzcyk,&nbsp;Liang Xiao,&nbsp;Hanlin Zhou,&nbsp;Guibo Li,&nbsp;Karsten Kristiansen,&nbsp;Lise Madsen","doi":"10.1002/mnfr.70573","DOIUrl":"10.1002/mnfr.70573","url":null,"abstract":"<p>Diets based on dairy or seafood proteins are reported to be less obesogenic than diets based on terrestrial meat proteins. The metabolic pathways underlying these differences, including processes related to thermogenesis, remain incompletely understood. Here, we investigated responses at levels of the transcriptome and the metabolome associated with potentially obesogenic high-fat, high-protein diets using casein, cod, or chicken as protein sources in mice kept at thermoneutral conditions or room temperature to evaluate metabolic responses to different housing temperatures. By performing plasma metabolomics analyses combined with RNA sequencing and gene set enrichment analyses of liver, muscle, white- and brown adipose tissue, we aimed to decipher the metabolic output and pathways modulated by intake of different dietary proteins. Dietary protein intake of casein, cod, or chicken led to differences in obesity development independent of housing temperature. The diet-specific phenotype was associated with a distinct plasma lipid profile and transcriptomic profile in liver and adipose tissue. One-carbon metabolism emerged as a potentially affected key pathway, and the mechanistic target of rapamycin complex 1/2 appeared as a predicted upstream regulator and accordingly suggested to be associated with protein source-dependent differences in obesity development and related metabolic disturbances.</p>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"70 15","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13454709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148700123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Daidzein Mitigates Nicotine-Induced Atherogenesis via Nrf2/ROS/TXNIP-Dependent Inhibition of Macrophage Pyroptosis and Lipid Accumulation","authors":"Xiao-Dan Xu,&nbsp;Kun Ren,&nbsp;Xian Liu,&nbsp;Hui-Hui Wang,&nbsp;Xin-Yu Lan,&nbsp;Lin Zhu,&nbsp;Meng-Qing Ma,&nbsp;Wen-Wu Luo","doi":"10.1002/mnfr.70570","DOIUrl":"10.1002/mnfr.70570","url":null,"abstract":"<div>\u0000 \u0000 <p>Food-derived 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-induced 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-sensitive signaling pathways. In human acute monocytic leukemia cell line (THP-1)-derived macrophages, DAI alleviated nicotine-induced pyroptosis, as evidenced by the downregulation of NOD-like receptor family pyrin domain-containing 3 (NLRP3), ASC, cleaved caspase-1, and gasdermin D (GSDMD)-N, accompanied by reduced secretion of interleukin (IL)-1β, IL-6, and IL-18, and decreased lactate dehydrogenase (LDH) release and caspase-1 activity. DAI also enhanced (7-nitrobenz-2-oxa-1,3-diazole)-cholesterol (NBD)-cholesterol efflux, suppressed DiI-labeled oxidized low-density lipoprotein (DiI-ox-LDL) uptake, and mitigated intracellular lipid droplet accumulation. Mechanistically, silencing nuclear factor erythroid 2–related factor 2 (Nrf2), inducing reactive oxygen species (ROS), or overexpressing thioredoxin-interacting protein (TXNIP) abolished the protective effects of DAI, confirming the involvement of the Nrf2/ROS/TXNIP pathway. In nicotine-exposed apolipoprotein E-deficient (apoE^−/−) mice, DAI upregulated vascular Nrf2, downregulated TXNIP and pyroptosis-related 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-induced atherogenesis. These findings provide preclinical evidence for the potential of DAI as a food-derived bioactive compound for smoking-related AS.</p>\u0000 </div>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"70 15","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148700205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}