Food & Function最新文献

{"title":"Vitamin D metabolites, genetic variants, and risk of cardiovascular diseases among individuals with newly diagnosed type 2 diabetes: a prospective study.","authors":"Tianyu Guo, Shiyu Zhao, Zijun Tang, Mingyuan Yang, Jinke Xiang, Kun Yang, Meian He, An Pan, Huiru Tang, Gang Liu","doi":"10.1039/d6fo02277d","DOIUrl":"10.1039/d6fo02277d","url":null,"abstract":"<p><p>Evidence regarding individual vitamin D metabolites and cardiovascular diseases (CVD) among individuals with type 2 diabetes (T2D) remains limited. This study aimed to investigate the prospective associations of plasma vitamin D metabolites with incident CVD among individuals with newly diagnosed T2D. This study included 1122 participants with newly diagnosed T2D from the Dongfeng-Tongji Cohort study in China. Plasma vitamin D metabolites were quantified using liquid chromatography-tandem mass spectrometry. Sixty single-nucleotide polymorphisms (SNPs) in genes involved in vitamin D metabolic pathways were genotyped. Incidence of CVD was ascertained <i>via</i> electronic health records. During 9284 person-years of follow-up, we documented 520 incident CVD cases. Higher concentrations of plasma 24,25(OH)₂D₃ and 25(OH)D₃ were associated with a lower risk of incident CVD; comparing the highest with the lowest quartiles, multivariable-adjusted HRs (95% CIs) were 0.71 (0.55, 0.92) and 0.74 (0.58, 0.96), respectively. After false discovery rate (FDR) correction for multiple comparisons, the inverse association with 24,25(OH)₂D₃ remained statistically significant (<i>P</i>_FDR = 0.012), whereas the association with 25(OH)D₃ was marginally significant (<i>P</i>_FDR = 0.064). No significant associations were observed for 3-<i>epi</i>-25(OH)D₃ (0.81 [0.63-1.05]) or vitamin D₃ (0.97 [0.76-1.24]). Restricted cubic spline analysis suggested a potential nonlinear association between 25(OH)D₂ and CVD risk (<i>P</i> for overall = 0.007; <i>P</i> for nonlinearity = 0.002). In exploratory genetic analyses, nominal associations were observed for variants in CYP2R1 and CYP3A4, as well as for their potential interactions with vitamin D metabolites, although none remained significant after FDR correction. These findings suggest that vitamin D metabolites may have distinct associations with incident CVD among individuals with T2D, highlighting the importance of distinguishing individual vitamin D metabolites in CVD risk assessment. These findings warrant further validation in independent populations.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":"8702-8713"},"PeriodicalIF":6.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148987239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium cyclamate aggravates DSS-induced colitis in mice with associated microbial, metabolic, and epithelial alterations.","authors":"Haitao Wang, Yi Zhang, Yue Xing, Qiyuan Duan, Xu Pang, Jia Zhao, Zhifei Fu, Lifeng Han, Naiyun Mu, Liming Wang","doi":"10.1039/d6fo02315k","DOIUrl":"10.1039/d6fo02315k","url":null,"abstract":"<p><p>Sodium cyclamate is widely used as a non-nutritive sweetener, but its effects during intestinal inflammation remain poorly defined. We investigated whether chronic cyclamate exposure aggravated dextran sulfate sodium (DSS)-induced colitis in mice using disease phenotyping, 16S rRNA gene sequencing, targeted short-chain fatty acid and bile acid measurements, metabolomics, lipidomics, discovery proteomics, and independent western blot validation. Relative to DSS alone, DSS + Cyclamate mice exhibited greater disease severity and higher abundances of <i>Bacteroides</i> and <i>Klebsiella</i>; <i>Lactobacillus</i> and <i>Muribaculaceae</i> showed only nonsignificant downward trends in the direct comparison. Short-chain fatty acids and colonic bile acids did not differ significantly between DSS and DSS + Cyclamate, indicating that these changes provided contextual information rather than evidence for a primary cyclamate-specific pathway. The direct multi-omics comparison identified candidate alterations in central carbon and mitochondrial metabolism, purine metabolism, lipid remodeling, epithelial homeostasis, and redox defense. Western blotting confirmed lower Mucin-2, Occludin, glutathione peroxidase 2 (GPX2), and thioredoxin 2 (TXN2) abundance and higher total protein kinase C-β (PKC-β) abundance in DSS + Cyclamate mice. Changes in hypoxanthine, diacylglycerols (DAG), and cyclohexylamine supported testable hypotheses. These findings indicate that cyclamate exposure can aggravate DSS-induced colitis and identify microbial, epithelial, redox, and lipid-associated processes for causal validation.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":"8744-8761"},"PeriodicalIF":6.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149011748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chinese giant salamander (<i>Andrias davidianus</i>) skin-derived collagen peptides counteract UVB-induced skin photoaging through the miR-4521/EGFR/MAPK signaling axis.","authors":"Yongjie Zhou, Wenjing Xu, Giuseppe Valacchi, Chunyue Zhao, Yan Zhang, Zixin Fu, Yaru Li, Kai Wang, Hui Hong, Yongkang Luo, Bo Li, Yuqing Tan","doi":"10.1039/d6fo02738e","DOIUrl":"10.1039/d6fo02738e","url":null,"abstract":"<p><p>Dietary collagen peptides have been shown to alleviate UVB-induced skin photoaging. However, the upstream regulatory mechanisms and the bioactive peptide sequences underlying these effects remain unclear. In this study, using UVB-induced photoaging models in HaCaT cells and nude mice, we demonstrated that Chinese giant salamander-derived skin collagen peptides (CPs) ameliorate photoaging through the miR-4521/EGFR/MAPK axis and identified GPY (Gly-Pro-Try) as a representative anti-photoaging tripeptide. In HaCaT cells, UVB irradiation downregulated miR-4521. Bioinformatics and transfection analyses suggested that EGFR is regulated by miR-4521 and functions as an upstream regulator of the MAPK pathway. CPs treatment increased miR-4521, inhibited EGFR and MAPK activation, and consequently ameliorated photoaging-related phenotypes. Compared with UVB irradiation alone, GPY increased the expression of type I collagen and elastin in HaCaT cells by 61.9 and 10.0%, respectively, while suppressing MAPK activation. In nude mice exposed to UVB for 10 weeks, dermal collagen fibers became disorganized, and the collagen area and type I collagen level decreased to approximately 20 and 10% of the corresponding control values, respectively. Dietary CPs intervention restored collagen fiber organization and increased the collagen area and type I collagen to 66.7 and 76.0% of the control levels, respectively. CPs supplementation also suppressed MAPK signaling, as evidenced by reductions of 22.3, 81.3, and 44.7% in p-JNK, p-ERK, and p-p38 levels, respectively, relative to the UVB-only group. Overall, these findings reveal the miR-4521/EGFR/MAPK axis and GPY as key bases for the anti-photoaging effects of CPs.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":"8495-8510"},"PeriodicalIF":6.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148758405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Food bioactives and extracellular vesicles: a narrative review.","authors":"Domitille Lelong, Thomas Payet, Julien Astier, Flavie Sicard, Jean-François Landrier, Lourdes Mounien","doi":"10.1039/d6fo03815h","DOIUrl":"10.1039/d6fo03815h","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are now recognized as key mediators of intercellular communication, transferring cargos such as proteins, lipids, and nucleic acids between cells and thereby influencing physiological and pathological processes. While the role of EVs has been extensively investigated in physiological and pathophysiological contexts, nutrition has only recently been recognized as an important modulator of endogenous EV biology. Emerging evidence indicates that nutrition and food bioactive compounds can influence EV biology through three distinct mechanisms: (i) modulation of the biogenesis, release, cargo composition and biological activity of endogenous host-derived EVs; (ii) use of EVs as vehicles for the systemic transport of food bioactives and their metabolites; and (iii) delivery of exogenous, diet-derived vesicles such as plant- and bacteria-derived EVs. This review synthesizes the current evidence on the interactions between major classes of dietary bioactives including polyphenols, fatty acids, vitamins, and carotenoids and EV biology.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":"8445-8454"},"PeriodicalIF":6.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148899779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The intake of tomato juice and lycopene modulates expression of human plasma microRNAs: a randomized, double-blind, parallel-group study.","authors":"Mao Yamamoto, Yoshinori Fujimura, Ryotaro Chiba, Shinya Hirakawa, Motofumi Kumazoe, Akane Haseda, Jun Nishihira, Mari Maeda-Yamamoto, Hirofumi Tachibana","doi":"10.1039/d6fo02604d","DOIUrl":"10.1039/d6fo02604d","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) regulate biological responses by targeting specific mRNAs. Although miRNA expression is altered by diseases and lifestyle factors, the effects of food intake on miRNA expression in humans remain unclear. Here we investigated the effects of tomato juice (T) and lycopene contained in T on miRNA levels in humans. This randomized, double-blind placebo-controlled trial included 22 healthy Japanese individuals. Participants consumed either T or lycopene-deleted tomato juice (LDT) for 12 weeks, and their comprehensive plasma miRNAs were assessed using next-generation sequencing. The intake of T increased the expression of 14 miRNAs and decreased that of 21 miRNAs. Differential analysis between T and LDT revealed that lycopene contained in T increased the expression of three miRNAs, miR-28-5p, miR-128-3p, and miR-186-5p, and decreased the expression of two miRNAs, miR-197-3p and miR-92a-3p. These data provide the first evidence that tomato juice and lycopene intake may alter miRNA expression in humans.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":"8762-8774"},"PeriodicalIF":6.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149011746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated molecular networking and AI modeling reveal xanthine oxidase-inhibitory flavonoids from the edible plant <i>Gnaphalium affine</i> D. Don.","authors":"Sen Mei, Xinchao He, Jin Qian, Lijuan Rao, Jiajing Liao, Chen Wang, Tao Wu, Haowei Fan, Guiming Fu, Yin Wan","doi":"10.1039/d6fo01328g","DOIUrl":"10.1039/d6fo01328g","url":null,"abstract":"<p><p>Hyperuricemia, a diet-related metabolic disorder, is primarily managed by targeting xanthine oxidase (XOD), the central enzyme responsible for uric acid production. Conventional screening of natural XOD inhibitors often struggles to deconvolute complex food-derived metabolomes. Here, we establish an integrated framework coupling data-driven feature-based molecular networking (FBMN) with AI-assisted ColabFold structural modeling for the rapid discovery of XOD-inhibitory flavonoids. Applied to the edible plant <i>Gnaphalium affine</i> D. Don, this approach enabled the high-resolution annotation of 65 flavonoids, including 56 previously unreported in this species. Kaempferol 3,4'-diglucoside emerged as the most potent candidate, exhibiting strong structural complementarity to the XOD catalytic center (docking interaction energy = -68.1 kcal mol^-1) and potent <i>in vitro</i> inhibitory activity (IC₅₀ = 14.1 ± 0.8 μM). Structural analysis further revealed a multimodal binding mechanism, in which di-glycosylation enhances binding stability and affinity, providing new insights into the structure-activity relationships of flavonoids. Beyond validating <i>G. affine</i> as a functional dietary source, this study offers a scalable, data-driven strategy for the prioritization of potential candidates that may inform the future development of mechanism-oriented functional food ingredients from complex food matrices.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":"8511-8527"},"PeriodicalIF":6.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calcium homeostasis as a food-science framework linking food-derived nutrients and bioactive compounds to glucose regulation and metabolic health.","authors":"Jing Wang, Rui Liu, Chong Wang, Minjie Zhao, Fengqin Feng, Linglin Fu","doi":"10.1039/d6fo02927b","DOIUrl":"10.1039/d6fo02927b","url":null,"abstract":"<p><p>Calcium homeostasis is increasingly recognized as a mechanistic hub linking food-derived nutrients, bioactive compounds, gut-derived signals, and host glucose regulation. However, existing reviews have generally examined dietary bioactives, the gut microbiota, or metabolic disorders separately, without establishing calcium signaling as an integrated food-science framework. This review critically evaluates current evidence on how food-derived nutrients and bioactive compounds influence calcium homeostasis and calcium-dependent signaling in metabolically relevant tissues, including intestinal enteroendocrine cells, pancreatic β-cells, liver, adipose tissue, and skeletal muscle. Particular attention is given to food sources, gut microbiota interactions, food matrix effects, processing and storage influences, and the physiological relevance of dietary exposure. Available evidence indicates that selected food components may modulate calcium-sensing receptor signaling, transient receptor potential channels, voltage-gated calcium influx, endoplasmic reticulum calcium handling, and gut-derived mediators such as short-chain fatty acids and bile acid-related pathways. These mechanisms may influence incretin secretion, insulin secretion, insulin sensitivity, inflammatory tone, and hepatic glucose metabolism. However, the strength of evidence varies substantially across food components, tissues, and experimental models, and many reported effects rely on isolated compounds, nonphysiological doses, or limited <i>in vivo</i> validation. Current knowledge is also constrained by insufficient consideration of the food matrix, bioaccessibility, host-microbial cometabolism, and realistic consumption conditions, particularly the use of non-physiological <i>in vitro</i> concentrations and the lack of validation in whole-food matrices under realistic intake scenarios. Positioning calcium homeostasis as a food-science mechanism may improve the interpretation of the metabolic health effects of food components and help identify physiologically achievable calcium-signaling targets, matrix-aware formulations, and consumption-relevant strategies for functional food design.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":"8455-8482"},"PeriodicalIF":6.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148899734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flavonoid-rich foods and vascular functions in healthy adults: a systematic review and meta-analysis of randomized controlled trials.","authors":"Arya Ega Prakasa, Ketut Wahyu Adi Saputra, Aloysius Denzel Joshua Reviano, Adrian Faza Raditya, Hendro Kusumo Sricahyonoaji, Citrawati Dyah Kencono Wungu, Hendri Susilo, Mohd Ramadan Ab Hamid","doi":"10.1039/d6fo03299k","DOIUrl":"10.1039/d6fo03299k","url":null,"abstract":"<p><p>Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide. Extensive research into preventive nutritional strategies against CVDs is needed. This meta-analysis aims to systematically evaluate the effects of flavonoid-rich foods on vascular function in healthy adults. A systematic literature search was conducted on PubMed, ScienceDirect, Scopus, Wiley, and EBSCO, and was supplemented with unpublished trials obtained from ClinicalTrials.gov until June 10, 2026. Risk of bias was assessed using the Cochrane RoB 2.0 tool. Pooled random-effects results were analysed using RStudio 4.5.3. Heterogeneity was assessed and quantified using Higgins' <i>I</i>² statistics. A total of 11 randomized controlled trials comprising 561 healthy participants met the eligibility criteria. The flavonoid-rich food intake group exhibited a statistically significant improvement in flow-mediated dilation compared to the control group [MD = 1.58%; 95% CI: 0.90 to 2.27%; <i>P</i> < 0.0001, <i>I</i>² = 75.7%]. The carotid-femoral pulse wave velocity also showed a statistically significant improvement in the intervention group [MD = -0.28 m s^-1; 95% CI: -0.52 to -0.04 m s^-1; <i>P</i> = 0.0197, <i>I</i>² = 0%], although findings were not robust across leave-one-out and correlation coefficient sensitivity analyses. There was no significant change in systolic blood pressure (<i>P</i> = 0.2210) and diastolic blood pressure (<i>P</i> = 0.2294) among both groups. Overall, consumption of flavonoid-rich foods improves surrogate biomarkers of vascular function in healthy adults. Further large-scale trials are needed to establish optimal flavonoid subclasses, dosages, and intervention durations.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":"8483-8494"},"PeriodicalIF":6.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148917573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative anti-obesity efficacy of high-interest natural products in preclinical models: a bibliometric and network meta-analysis.","authors":"Ye-Xin Chen, Qian-Wen Yang, Lin Zhang, Mo-Han Sun, Hua-Yi Tong, Yi-Yu Dong, Yu-Xin Hu, Li Jiang, Jiang-Teng Liu, Jin-Xi Zhao","doi":"10.1039/d6fo03150a","DOIUrl":"10.1039/d6fo03150a","url":null,"abstract":"<p><p><i>Objective</i>: to identify research hotspots in natural products for obesity and compare their relative efficacy in preclinical models. <i>Methods</i>: bibliometric analysis was performed using CiteSpace and Bibliometrix on publications from the Web of Science Core Collection and PubMed up to January 31, 2026, to identify the five most frequently studied natural products. A systematic review and network meta-analysis (NMA) of animal studies evaluating monotherapy with these five natural products were conducted. The primary outcomes were body weight and epididymal white adipose tissue (eWAT), while secondary outcomes included fasting blood glucose (FBG), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Random-effects consistency models were used for data synthesis. Treatment rankings were estimated using the Surface Under the Cumulative Ranking (SUCRA) curve. Meta-regression and subgroup analyses were performed to explore heterogeneity. <i>Results</i>: bibliometric analysis identified 4598 publications. The NMA included 137 studies and 2512 animals. Berberine, resveratrol, quercetin, anthocyanins, and curcumin were the most studied. All five natural products significantly reduced body weight <i>versus</i> control. SUCRA rankings suggested outcome-specific ranking patterns within the current evidence network. Berberine showed the highest ranking probability for body weight (92.2%), eWAT (96.3%), and HDL-C (82.1%). Anthocyanins ranked the highest for TC and resveratrol ranked the highest for FBG and LDL-C. Meta-regression identified the route of administration as a significant effect modifier for several outcomes. Subgroup analysis in terms of the administration route confirmed that findings in the subgroup were generally consistent with those from the main analysis. <i>Conclusion</i>: this integrative study maps the research landscape and summarizes comparative preclinical evidence on natural product-derived interventions in obesity models.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":"8623-8648"},"PeriodicalIF":6.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148943965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ameliorating effect of α-glycosyl isoquercitrin treatment from gestation on disruption of hippocampal neurogenesis induced by maternal exposure to imidacloprid in rats.","authors":"Xinyu Zou, Yuri Ebizuka, Qian Tang, Yuri Sakamaki, Momoka Shobudani, Tetsuhito Kigata, Gye-Hyeong Woo, Mihoko Koyanagi, Makoto Shibutani","doi":"10.1039/d6fo01737a","DOIUrl":"10.1039/d6fo01737a","url":null,"abstract":"<p><p>There is a growing concern about developmental brain impairment following exposure to neonicotinoid pesticides. Experimentally, imidacloprid (IMI), a representative neonicotinoid pesticide, impairs postnatal hippocampal neurogenesis in rat offspring after maternal exposure. This study examined how IMI disrupts neurogenesis and whether the synthetic flavonoid α-glycosyl isoquercitrin (AGIQ) can counteract these effects through its antioxidant action. Maternal rats were given a diet containing 750 ppm IMI and drinking water with or without 0.3% AGIQ from gestation day 6 until weaning on day 21 post-delivery. Then, male offspring similarly received AGIQ until postnatal day 77 or 79 during adulthood. Continuous AGIQ exposure restored IMI-suppressed neurogenesis and proliferation of neural progenitor cells, granule cell synaptic plasticity, the numbers of reelin⁺ and calbindin-D-29K⁺ GABAergic interneurons, and BDNF-TrkB signaling in the dentate gyrus at weaning, improving spatial memory. In adulthood, AGIQ also reversed IMI-induced persistent deficits in neurogenesis, synaptic plasticity, and BDNF-TrkB signaling. AGIQ normalized the IMI-induced immunocompromised state (evidenced by downregulation of pro-inflammatory cytokine genes but an increase in the number of pro-inflammatory microglia/macrophages) by increasing acetylcholinesterase activity at weaning. AGIQ also recovered the IMI-induced suppression of antioxidant capacity observed at weaning by restoring antioxidant gene expression and elevating the reduced glutathione/oxidized glutathione ratio in adulthood. Overall, maternal IMI exposure caused immunosuppression and heightened oxidative stress sensitivity in the dentate gyrus, disrupting neurogenesis and synaptic plasticity through suppression of the BDNF-TrkB pathway, as well as reelin and calbindin-D-29K⁺ interneuron signaling. AGIQ mitigated IMI-induced hippocampal immunosuppression and antioxidant system damage by enhancing acetylcholinesterase activity and antioxidant gene expression.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":"8563-8583"},"PeriodicalIF":6.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149014832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}