Food frontiers最新文献

{"title":"High-Dose Parenteral Iron Corrects Iron Deficiency Anemia While Disrupting Gut Microbiota and Metabolic Homeostasis in Neonatal Piglets","authors":"Qian Zhang,&nbsp;Yubin Hao,&nbsp;Xin Tian,&nbsp;Xuejiao Li,&nbsp;Jie Feng","doi":"10.1002/fft2.70160","DOIUrl":"10.1002/fft2.70160","url":null,"abstract":"<p>Iron deficiency anemia (IDA) is a common nutritional disorder in mammals, particularly affecting neonates and neonatal piglets. Parenteral iron supplementation is widely used but carries toxicity risks at high doses. Due to rapid growth and low iron stores at birth, piglets serve as an ideal model for investigating early life iron supplementation and its impact on gut health. In this study, neonatal piglets were assigned to three groups: control (CON, no iron supplementation), moderate-dose (MI, two low doses), and high-dose (HI, a single high dose), all administered via intramuscular iron dextran. We found that both iron supplementation protocols significantly increased hemoglobin levels (<i>p</i> &lt; 0.01) and effectively alleviated IDA. However, the HI group exhibited significant adverse effects, including elevated aspartate aminotransferase (AST) (<i>p</i> &lt; 0.01), suppressed anti-inflammatory cytokines (IL-10, <i>p</i> &lt; 0.01), and increased tissue iron accumulation, whereas the MI group showed no such adverse effects. Gut microbiota analysis revealed that the HI group disrupted the gut microbiota, with a greater impact on fungal diversity than bacterial diversity, as indicated by α-diversity metrics (<i>p</i> &lt; 0.05), and also altered the intestinal metabolite profiles. Protein–protein interaction network analysis identified key genera and metabolites, including <i>Fusarium</i>, <i>Geotrichum</i>, <i>Parabacteroides</i>, <i>Candida</i>, and cholest-4-en-3-one, associated with duodenal iron accumulation. This study demonstrates that although high-dose parenteral iron effectively corrects IDA, it causes liver dysfunction, immune suppression, systemic iron overload, and altered gut microbiota. Our findings highlight the importance of appropriate iron dosing and reveal broader roles of trace elements in shaping gut microbiota.</p>","PeriodicalId":73042,"journal":{"name":"Food frontiers","volume":"7 1","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://iadns.onlinelibrary.wiley.com/doi/epdf/10.1002/fft2.70160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145825114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Evidence From Metabolome-Wide Mendelian Randomization and Animal Models Implicates Tyrosine in Cardiac Hypercontractility and Arrhythmia Risk","authors":"Zhikang Cao,&nbsp;Huiying Liu,&nbsp;Peng Chen,&nbsp;Liyue Chen,&nbsp;Zhixin Chen,&nbsp;Jiaqiang Lin,&nbsp;Zixuan Fu,&nbsp;Zhipeng Li","doi":"10.1002/fft2.70143","DOIUrl":"10.1002/fft2.70143","url":null,"abstract":"<p>Arrhythmias account for approximately 80% of sudden cardiac deaths, posing a significant challenge to public health. Investigating the relationships between plasma metabolites and arrhythmia contributes to understanding disease etiology and informing therapeutic strategies. In this research, we accessed the causal links between 735 circulating metabolites and arrhythmias using Mendelian randomization (MR) across multiple genome-wide association studies (GWAS) datasets and meta-analyzed the results. Tyrosine showed the strongest putative causal association with arrhythmias and their risk factors. We further replicated this finding using independent GWAS data from FinnGen, providing additional support. Moreover, genetic loci associated with circulating tyrosine levels were significantly enriched for genes implicated in cardiovascular disease. To provide experimental support, we tested these predictions in an animal model. Transthoracic echocardiography demonstrated that tyrosine increased ejection fraction and fractional shortening, indicating enhanced cardiac systolic function. Transcriptomic analysis indicated that tyrosine activated adrenergic signaling in cardiomyocytes, which promotes cardiac conduction and muscle contraction. Consistently, tyrosine elevated serum epinephrine levels in a dose-dependent manner. Furthermore, metabolomic profiling showed that tyrosine altered serum metabolites previously linked to arrhythmias. In conclusion, convergent evidence from genetic analyses and animal experiments suggests that excessive dietary tyrosine induces cardiac hypercontractility, and circulating tyrosine may serve as a potential target for arrhythmia prevention.</p>","PeriodicalId":73042,"journal":{"name":"Food frontiers","volume":"7 1","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://iadns.onlinelibrary.wiley.com/doi/epdf/10.1002/fft2.70143","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145824608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the Impact of Withering Methods on Aroma Profile of White Peony Tea Through Integrating Metabonomics and Sensomics","authors":"Yingxin Xu,&nbsp;Xiaogan Chen,&nbsp;Liqing Mei,&nbsp;Hongying You,&nbsp;Zhenchuan Lin,&nbsp;Haowei Guo,&nbsp;Qiang Chu,&nbsp;Shuying Gong,&nbsp;Fangyuan Fan","doi":"10.1002/fft2.70128","DOIUrl":"10.1002/fft2.70128","url":null,"abstract":"<p>Withering is a critical processing step that significantly influences the aroma quality of white tea. Although various withering methods are known to alter the aroma profile of white tea, the causal relationship between specific withering parameters and the resulting aroma signature remains elusive. This study systematically investigated the effects of sunlight withering (SW) and dark withering (DW) on the aromatic profile of white peony tea (WPT) made from three tea cultivars. Comparative analysis revealed that SW significantly attenuated the intensity of green aroma in WPT. Through orthogonal partial least squares-discriminant analysis (OPLS-DA) combined with odor activity value (OAV) evaluation, a total of 12 aroma-active compounds were identified. Aroma recombination models constructed using these compounds successfully reproduced the balanced sensory profile of WPT, encompassing green, fresh, sweet, and fatty notes. Omission experiments further elucidated the critical role of five volatile compounds in mediating withering-induced aroma variations: Linalool, (<i>Z</i>)-3-hexen-1-ol, (<i>E</i>)-2-hexenal, benzeneacetaldehyde, and <i>β</i>-ionone. These findings provide novel insights into the mechanisms of aroma modulation by different withering processes in WPT production.</p>","PeriodicalId":73042,"journal":{"name":"Food frontiers","volume":"7 1","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://iadns.onlinelibrary.wiley.com/doi/epdf/10.1002/fft2.70128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145824612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Lysozyme Transgenic Maize Improves Colonic Inflammation by Inhibiting the cGAS/STING Signaling Pathway in DSS-Induced Colitis Mice","authors":"Yinuo Yu,&nbsp;Yaqin Li,&nbsp;Xuan Chen,&nbsp;Rentao Song,&nbsp;Zhenyi Qiao,&nbsp;Weiwei Qi","doi":"10.1002/fft2.70149","DOIUrl":"10.1002/fft2.70149","url":null,"abstract":"<p>Inflammatory bowel disease (IBD) is a refractory condition caused by autoimmune disorders. The recurrent nature and poor prognosis of this disease necessitate long-term treatment, substantially increasing the financial burden on patients. Human lysozyme (HLZ) possesses the function of ameliorating intestinal inflammation. Meanwhile, maize is the world's most popular food crop, valued for its easy cultivation and low cost. In this study, the <i>HLZ</i> gene was introduced into maize. <i>HLZ</i> transgenic maize showed specific high accumulation of HLZ in kernels with no negative effect on maize yield, protein content and protein quality. Moreover, the total protein extracted from the transgenic endosperm exhibited strong lysozyme activity (291.15 U/mg). Using a dextran sulfate sodium (DSS)-induced colitis mouse model, we observed that <i>HLZ</i> transgenic maize restored colon length and intestinal barrier function in mice. The results of further molecular analyses indicated that <i>HLZ</i> transgenic maize inhibited intestinal epithelial cell apoptosis and altered the intestinal microbiota. Furthermore, <i>HLZ</i> transgenic maize inhibited the cGAS/STING signaling pathway by ameliorating DSS-induced mitochondrial dysfunction. In addition, the results of transcriptomic sequencing revealed that <i>HLZ</i> transgenic maize reversed DSS-induced alterations in the expression of genes related to colonic inflammation (e.g., <i>IFN-β</i> and <i>IL6</i>). This research deepened the understanding of the functional mechanisms for HLZ in improving intestinal immune system. Our results indicate that <i>HLZ</i> transgenic maize provides an effective and low-cost approach for clinically ameliorating IBD symptoms. As a food resource, <i>HLZ</i> transgenic maize might benefit a wider range of people than drugs.</p>","PeriodicalId":73042,"journal":{"name":"Food frontiers","volume":"7 1","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://iadns.onlinelibrary.wiley.com/doi/epdf/10.1002/fft2.70149","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Henan and Gansu Starter Cultures Microbial Diversity on Structure and Flavor Property of Mung Bean Bread","authors":"Xiaoming Wang,&nbsp;Xiling Zhang,&nbsp;Lu Kong,&nbsp;Weichao Guan,&nbsp;Chanmin Zheng,&nbsp;Dan Yang,&nbsp;Guoqi Na,&nbsp;Chenqi Gu,&nbsp;Qingyu Yang,&nbsp;Yuguang Zhang","doi":"10.1002/fft2.70091","DOIUrl":"10.1002/fft2.70091","url":null,"abstract":"<p>This study examined the fermentation mechanism of Gansu starter cultures (GSSC) and Henan starter cultures (HNSC), each mixed with yeast, in enhancing the distinctive flavor of bread. High-throughput sequencing analysis revealed that 157 bacterial genera and 53 fungal genera were identified in the GSSC, while the HNSC comprised 29 bacterial genera and 35 fungal genera. The data confirmed that the levels of lactic acid and exopolysaccharides (EPS) increased during the mung bean sourdough fermentation process with GSSC and HNSC, contributing to improved dough fermentation properties. The results of scanning electron microscopy and disulfide bond analysis indicated improved gluten network formation in Gansu mung bean dough (GMD) and Henan mung bean dough (HMD). The FT-IR data revealed that Gansu mung bean sourdough bread (GMB) and Henan mung bean sourdough bread (HMB) each exhibited a stable protein secondary structure, which enhanced specific volume and texture property. Specifically, the specific volume of GMB and HMB increased by 35.38% and 67.69%, respectively, compared to the regular mung bean bread. Gas chromatography-ion mobility spectrometry (GC-IMS) analysis of bread identified 42 key volatile compounds. Correlation analysis showed that GMB developed citrus and burnt popcorn aromas, while HMB presented fruity and floral notes. These new findings would provide theoretical basis for using new starter cultures for enhancing both the quality and flavor of mung bean bread.</p>","PeriodicalId":73042,"journal":{"name":"Food frontiers","volume":"7 1","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://iadns.onlinelibrary.wiley.com/doi/epdf/10.1002/fft2.70091","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145845980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selenium-Enriched Matcha Ameliorates Alcohol-Induced Liver Injury by Modulating Cytochrome P450 Expression in Mice","authors":"Zhuo-Wen Su,&nbsp;Xiao-Hua Yang,&nbsp;Hua-Feng Zhang,&nbsp;Lu Li,&nbsp;Si-Yu Deng,&nbsp;Zhi-Chen Mo","doi":"10.1002/fft2.70145","DOIUrl":"10.1002/fft2.70145","url":null,"abstract":"<p>Selenium is an essential trace element for human health, and the selenium content in selenium-enriched matcha meets the official criteria for selenium-enriched foods in China. In the present work, hepatoprotective effects of selenium-enriched matcha against alcohol-induced liver injury were systematically investigated, and its mechanism was explored by label-free proteomic technique for the first time. When fed with selenium-enriched matcha, selenium was distributed in various organs and tissues (heart, liver, spleen, lung, kidney, serum, and muscle), and the selenium content in the liver was significantly higher than that in other organs and tissues (<i>p</i> &lt; 0.05). Levels of alanine transaminase, aspartate transaminase, total cholesterol, triglyceride, total bilirubin, and malondialdehyde in selenium-enriched matcha intervention groups were lower than those in the alcohol model (AM) group, while levels of glutathione peroxidase, superoxide dismutase, and glutathione in selenium-enriched matcha intervention groups were higher than those in the AM group. A total of 376 differentially expressed proteins (DEPs) were identified, in which 35 key DEPs were involved in 26 biological processes, 14 cellular components, and 14 molecular functions. Intervention with selenium-enriched matcha notably downregulated cytochrome P450 (Cyp2c40 and Cyp2c54), which specifically modulated pathways of chemical carcinogenesis-DNA adducts, arachidonic acid, and retinol metabolisms. These results provide evidence for the use of selenium-enriched matcha in alleviating alcohol-induced liver injury.</p>","PeriodicalId":73042,"journal":{"name":"Food frontiers","volume":"7 1","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://iadns.onlinelibrary.wiley.com/doi/epdf/10.1002/fft2.70145","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145845858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic Identification of Native Bacillus spp. as a Sustainable Approach to Mitigate Cadmium in Cocoa","authors":"Miguel Fernández-Niño,&nbsp;Juan Fernando Meza,&nbsp;Claudia M. Rodríguez-López,&nbsp;Maria Camila Buitrago-Acosta,&nbsp;Diana M. Cortes-Mera,&nbsp;María José Chica,&nbsp;Jorge Duitama,&nbsp;Duvan Albeiro Millan,&nbsp;Andrés Díaz-García,&nbsp;Eddy J. Bautista,&nbsp;Andrés Fernando González Barrios","doi":"10.1002/fft2.70131","DOIUrl":"10.1002/fft2.70131","url":null,"abstract":"<p>One of the most pressing challenges for the cocoa industry is cadmium (Cd) accumulation, which poses serious health risks and limits access to international markets. Notably, Cd concentrations in many cocoa products exceed the European Union's maximum permissible threshold of 0.60 mg kg⁻¹ in finished chocolate, threatening exports and farmer livelihoods. Previous studies have explored different methods for Cd remediation; however, they have been found to be costly and inefficient at the Cd concentrations typical of cocoa. Microorganisms, such as <i>Bacillus</i> spp., offer a promising alternative for Cd bioremediation during cocoa processing. In this study, we present a systematic screening of natural <i>Bacillus</i> isolates from cocoa fermentations as a sustainable approach for Cd remediation. Our multidisciplinary approach, integrating metagenomics, in vitro functional assays, microscopic imaging, genome sequencing, phylogenetic analysis, and functional annotation underscores the potential <i>of Bacillus</i> spp. as an effective, scalable, and natural solution for Cd mitigation. <i>Bacillus</i>, a dominant genus in industrial cocoa fermentations, exhibited diverse Cd tolerance profiles across 69 natural isolates. Notably, we identified two isolates—<i>Bacillus subtilis</i> Luk29 and <i>Bacillus paranthracis</i> Luk27—with demonstrated Cd removal capabilities in synthetic media under fermentation-relevant conditions. Growth kinetics were assessed under varying Cd concentrations, pH, and temperature conditions for Cd removal. Genome annotation revealed that both strains possess strong Cd resistance mechanisms, including efflux systems, ATPases, and MerR-family regulators. This work contributes to our understanding of microbial impacts on cocoa safety while providing a scalable strategy for enhancing the sustainability and marketability of cocoa products worldwide.</p>","PeriodicalId":73042,"journal":{"name":"Food frontiers","volume":"7 1","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://iadns.onlinelibrary.wiley.com/doi/epdf/10.1002/fft2.70131","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145825034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cold Plasma Processing of Chickpeas and Lentils Increases Water Transport Into Grains and Results in Softer Texture After Cooking","authors":"Rabin Duwal,&nbsp;Bryan R. Coad","doi":"10.1002/fft2.70124","DOIUrl":"10.1002/fft2.70124","url":null,"abstract":"<p>Dried legumes require processing before they are soft enough for consumption. This study investigated the use of cold plasma pre-treatments on chickpea and lentil grains to improve their textural properties after cooking. Low temperature plasma treatments were conducted in a rotating plasma reactor. After plasma treatment, graphs of water uptake showed greatly changed hydration, with quantitative measures of water transport modeled to show substantial increases to both the rate of water entry into the grains and the total amount of water imbibed. When cooked, the measured textural properties (hardness, cohesiveness, chewiness, and resilience) had also changed. Softening of cooked grains after plasma treatment can be explained by the improved water penetration pre-cooking caused by plasma's ability to etch the outer seed coat of legumes. Surface analysis by scanning electron microscopy (SEM) and x-ray photoelectron spectroscopy (XPS) indicated changes to the physicochemical properties of the seed coat, with notable removal of waxes, exposure of tissue layers, and surface oxidation. Identical plasma treatments affected the hydration properties of chickpeas and lentils differently. This evidence suggests that the different biological makeup of chickpeas or lentils is important to consider, because the way in which plasma interacts with the outer surfaces (seed coats) of grains can be quite different for different foods. Future studies where plasma is used as a food processing technology will benefit from detailed surface analysis and quantification of water transport coefficients as a robust methodology for understanding how to apply effective plasma treatments.</p>","PeriodicalId":73042,"journal":{"name":"Food frontiers","volume":"7 1","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://iadns.onlinelibrary.wiley.com/doi/epdf/10.1002/fft2.70124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering Gossypol-Free Cottonseeds for Future Global Food Security and Agricultural Sustainability","authors":"Teame Gereziher Mehari,&nbsp;Muhammad Yousaf Shani,&nbsp;Junfeng Tang,&nbsp;Hui Fang,&nbsp;Muhammad Jawad Umer,&nbsp;Fang Liu,&nbsp;Kai Wang,&nbsp;Dengbing Yao,&nbsp;Muhammad K. R. Khan,&nbsp;Baohua Wang","doi":"10.1002/fft2.70138","DOIUrl":"10.1002/fft2.70138","url":null,"abstract":"<p>Cottonseed, a protein and oil rich byproduct of cotton (<i>Gossypium</i> spp.) fiber production, represents a valuable but underexploited food and feed resource. Its utilization is severely constrained by the presence of gossypol, a toxic sesquiterpenoid aldehyde that accumulates in seeds but plays a critical defensive role in vegetative tissues. Recent advances in biotechnology have enabled precise manipulation of gossypol biosynthesis and gland formation, offering strategies to decouple nutritional quality from plant defense. Targeted approaches such as CRISPR/Cas9 mediated genome editing, RNA interference (RNAi), and virus-induced gene silencing (VIGS) have successfully surpassed key regulators, including <i>GoPGF</i> and <i>CGP1</i>, resulting ultralow gossypol cottonseed (ULGCS) while maintaining protective gossypol levels in leaves and stems. Stable transmission of these traits across generations positions cotton as a dual-purpose crop that simultaneously provides fiber and safe, high-quality protein. Integrating ULGCS into food systems could alleviate protein malnutrition, potentially benefiting over 500 million people annually, while also expanding the $7.4 billion global cottonseed oil market. Future research should integrate multi-omics, precision breeding, genomic selection, and advanced genome engineering to further enhance ULGCS nutritional value, seed composition, and agronomic performance. In addition, assessing metabolic trade-offs and ecological implications will be critical to ensure long-term sustainability. Reprogramming cottonseed gossypol content thus represents a transformative strategy at the interface of plant biotechnology, food security, and sustainable agriculture.</p>","PeriodicalId":73042,"journal":{"name":"Food frontiers","volume":"7 1","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://iadns.onlinelibrary.wiley.com/doi/epdf/10.1002/fft2.70138","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145845924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural Products Targeting the EGFR/HER2 Axis in Tumorigenesis: Interpretation of Molecular Mechanisms and Recent Insights Into Synergistic Strategies for Cancer Therapy","authors":"Iman Ramli,&nbsp;Anna Maria Posadino,&nbsp;Roberta Giordo,&nbsp;Antonio Barberis,&nbsp;Ylenia Spissu,&nbsp;Redouane Lemoui,&nbsp;William N. Setzer,&nbsp;Javad Sharifi-Rad,&nbsp;Gianfranco Pintus","doi":"10.1002/fft2.70135","DOIUrl":"10.1002/fft2.70135","url":null,"abstract":"<p>The epidermal growth factor receptor (EGFR/HER1) and human epidermal growth factor receptor 2 (HER2) are key members of the ErbB tyrosine kinase receptor family, playing central roles in the pathogenesis of various cancers, including breast, lung, colorectal, and gastric tumors. Their overexpression and activation drive tumor progression, metastasis, and resistance to therapies. Although several EGFR/HER2-targeted drugs, such as lapatinib, trastuzumab, and afatinib, have been developed, resistance and off-target toxicities necessitate novel therapeutic strategies. Natural products have emerged as promising candidates for modulating EGFR/HER2 signaling due to their structural diversity, multitarget potential, and favorable safety profiles. This review provides an overview of natural modulators from phenolics, terpenoids, alkaloids, glycosides, saponins, and marine compounds that inhibit EGFR and/or HER2 by blocking phosphorylation, disrupting dimerization, promoting degradation, or modulating downstream pathways such as PI3K/Akt/mTOR, MAPK/ERK, and STAT3. Compounds like curcumin, epigallocatechin gallate (EGCG), resveratrol, quercetin, and berberine demonstrate both direct and synergistic anticancer effects in vitro and in vivo, especially when combined with chemotherapy or radiation. Emphasis is given to dual-targeting strategies, where natural compounds inhibit both EGFR and HER2, overcoming monotherapy resistance. Molecular docking and in silico simulations further support their binding affinity for ATP-binding domains of tyrosine kinases. This review also highlights combinatorial approaches using dietary phytochemicals and synthetic inhibitors, paving the way for integrative oncology. In conclusion, natural compounds are valuable bioactive agents with potential to complement EGFR/HER2-targeted therapies. Future efforts should improve bioavailability, elucidate mechanisms, and validate efficacy through clinical studies.</p>","PeriodicalId":73042,"journal":{"name":"Food frontiers","volume":"7 1","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://iadns.onlinelibrary.wiley.com/doi/epdf/10.1002/fft2.70135","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145824613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}