Food frontiersPub Date : 2026-06-11DOI: 10.1002/fft2.70269
Fakhar Shahid, Ifrah Jabeen, Muhammad Inam-ur-Raheem, Amin Mousavi Khaneghah, Muhammad Abid, Rana Muhammad Aadil
{"title":"Therapeutic Potential of Berberis vulgaris in Modulating Metabolic Syndrome Biomarkers: Mechanistic Insights and Functional Food Implications","authors":"Fakhar Shahid, Ifrah Jabeen, Muhammad Inam-ur-Raheem, Amin Mousavi Khaneghah, Muhammad Abid, Rana Muhammad Aadil","doi":"10.1002/fft2.70269","DOIUrl":"https://doi.org/10.1002/fft2.70269","url":null,"abstract":"<p>Barberry (<i>Berberis vulgaris</i>) has emerged as a promising functional food candidate for the management of metabolic syndrome due to its diverse bioactive constituents, particularly berberine. This review synthesizes current experimental and clinical evidence regarding its effects on glycemic control, lipid metabolism, blood pressure regulation, and obesity-related parameters. Mechanistic insights indicate that barberry improves insulin sensitivity, enhances glucose uptake, suppresses hepatic gluconeogenesis, modulates lipid metabolism, and exerts antioxidant and anti-inflammatory effects. Clinical findings suggest potential benefits in lowering fasting blood glucose, triglycerides, low-density lipoprotein cholesterol, blood pressure, and central adiposity. In addition, synergistic interactions among alkaloids, flavonoids, and carotenoids may contribute to its multifunctional therapeutic profile. Despite these promising outcomes, evidence remains heterogeneous, and rigorously designed, large-scale randomized controlled trials are required to establish standardized dosing regimens, confirm long-term safety, and support evidence-based clinical integration.</p>","PeriodicalId":73042,"journal":{"name":"Food frontiers","volume":"7 4","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/fft2.70269","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148237865","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":"Analysis and Predictive Modeling of In Vitro Digestive Stability of Tea Polyphenols in 24 Tea Varieties","authors":"Xinyi Li, Jingling Kang, Weiyao Wu, Huifan Liu, Yuming Zhong","doi":"10.1002/fft2.70276","DOIUrl":"https://doi.org/10.1002/fft2.70276","url":null,"abstract":"<p>Tea polyphenols (TP) constitute key functional components in tea leaves, yet their instability during human digestion limits absorption. This study selected 24 representative tea varieties to establish an in vitro dynamic digestion model, investigating the dynamic changes of TP during digestion. Characteristic signals of tea liquor were collected using electronic nose and color difference technology to construct predictive models, enabling the estimation of TP content (TPC) before and after digestion. Results indicate the tea liquor aroma is dominated by hydrogen compounds, and tea fermentation level correlates positively with liquor color intensity. Green tea exhibits the highest TPC and catechin levels, demonstrating potent antioxidant properties. TP remains relatively stable in the stomach but is significantly reduced in the intestine, whilst the catechin components exhibit distinct degradation patterns. The Extreme Gradient Boosting (XGBoost) model predicting TPC based on electronic nose data demonstrated the highest efficacy, with an <i>R</i><sup>2</sup>: 0.92. The XGBoost model incorporating color difference and TPC achieved the best performance, with an <i>R</i><sup>2</sup>: 0.81. This research provides robust support for elucidating TP digestion patterns in humans and establishing a tea quality assessment system.</p>","PeriodicalId":73042,"journal":{"name":"Food frontiers","volume":"7 4","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/fft2.70276","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148173993","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":"Inonotus obliquus Ameliorates Metabolic Dysfunction and Attenuates Obesity by Enriching Enterococcus casseliflavus","authors":"Xiao Sun, Xuliang Wei, Meng Dong, Haoyang Liu, Tengyu Zhu, Yangming Zhang, Longhui Wang, Yongchun Li, Hongde Xu","doi":"10.1002/fft2.70308","DOIUrl":"https://doi.org/10.1002/fft2.70308","url":null,"abstract":"<p>Obesity has emerged as a growing global epidemic, substantially increasing the risk of several diseases. <i>Inonotus obliquus</i> (IO) is a traditional edible and medicinal mushroom known to ameliorate hyperglycemia and hyperlipidemia. However, its effects on the gut microbiota and the underlying mechanisms remain elusive. Here, we investigated the anti-obesity effects of IO and explored gut microbiota-mediated mechanisms using a high-fat diet (HFD)-induced obese mouse model. Fecal microbiota transplantation (FMT) and 16S rRNA gene sequencing were performed, followed by <i>Enterococcus casseliflavus</i> (EC) intervention experiments. IO administration markedly reduced HFD-induced obesity without altering energy intake. Recipient mice that received FMT from IO-treated donors exhibited anti-obesity and thermogenic effects, indicating a transferable role of the gut microbiota. EC was significantly enriched following IO treatment, and EC intervention alone recapitulated the metabolic benefits of IO, including increased energy expenditure and enhanced thermogenic gene expression in both brown and white adipose tissues, accompanied by upregulation of uncoupling protein 1 (UCP1) and oxidative phosphorylation-related proteins. Notably, EC was only transiently detectable in the gut but still improved systemic metabolic homeostasis, strengthened intestinal barrier function, reduced inflammation, and induced substantial remodeling of the serum metabolome, with elevated mesaconic acid as a key anti-inflammatory metabolite. This study demonstrates that IO ameliorates obesity by enriching EC, which acts as a transient probiotic, highlighting EC as a potential therapeutic candidate for obesity.</p>","PeriodicalId":73042,"journal":{"name":"Food frontiers","volume":"7 4","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/fft2.70308","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148174003","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}
Food frontiersPub Date : 2026-06-04DOI: 10.1002/fft2.70310
Xingcai Gao, Qing Zhou, Baoting Liu, Jun Li, Jianhua Xie, Yi Chen, Chenxu Gong, Xiaobo Hu, Qiang Yu
{"title":"Polygonatum cyrtonema Polysaccharides-Derived Metabolic Meta Alleviates ALD via a Gut–Liver Axis–Mediated, Bifidobacterium pseudolongum–Driven Suppression of the AA Metabolism–MAPK Signaling Network","authors":"Xingcai Gao, Qing Zhou, Baoting Liu, Jun Li, Jianhua Xie, Yi Chen, Chenxu Gong, Xiaobo Hu, Qiang Yu","doi":"10.1002/fft2.70310","DOIUrl":"https://doi.org/10.1002/fft2.70310","url":null,"abstract":"<p><i>Polygonatum cyrtonema</i>, a traditional Chinese medicinal and edible herb, possesses potential liver-protecting activities. Its primary active component is fermented polysaccharides (PCP), which exhibit gut microbiota–modulating activity. However, the key metabolites derived from PCP under gut microbiota mediation, along with their hepatoprotective bioactivity and mechanism of action, remain to be elucidated. Our findings demonstrated that microbial fermentation of PCP generated specifically elevated levels of indoleacetic acid, indole-3-carbinol, and β-hydroxybutyrate. The PCP metabolic meta alleviated typical alcohol-related liver disease symptoms and reduced hepatic lipid accumulation. Meanwhile, it restored gut microbiota dysbiosis, specifically elevating the abundance of <i>Bifidobacterium pseudolongum</i>, which was negatively correlated with liver injury indices. Mechanistic studies demonstrated that the PCP metabolic meta reduced intestinal levels of arachidonic acid (AA) metabolites such as 3R-HETE, 12-HEPE, and PGE1 and suppressed hepatic AA metabolism via the gut–liver axis, thereby inhibiting the phosphorylation of JNK and p38 mitogen-activated protein kinase (MAPK), downregulating downstream transcription factors c-Jun and activating transcription factor 2 (ATF2), and attenuating inflammation. <i>B. pseudolongum</i> alone recapitulated these protective effects, inhibiting hepatic AA metabolism and MAPK signaling. Collectively, these findings provide a fresh perspective for investigating the interactions between natural bioactive polysaccharides and the gut microbiota in the context of liver protection.</p>","PeriodicalId":73042,"journal":{"name":"Food frontiers","volume":"7 4","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/fft2.70310","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148173992","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}
Food frontiersPub Date : 2026-06-04DOI: 10.1002/fft2.70294
Ke Zhang, Xingtao Zhou, Xujie Wang, Mingyong Xie
{"title":"Pyruvate Kinase M2 Mediates Apigenin-Induced Energy Crisis and Apoptosis in Colon Cancer Cells","authors":"Ke Zhang, Xingtao Zhou, Xujie Wang, Mingyong Xie","doi":"10.1002/fft2.70294","DOIUrl":"https://doi.org/10.1002/fft2.70294","url":null,"abstract":"<p>Targeting tumor metabolism offers a promising therapeutic avenue for colon cancer. Our study demonstrated that apigenin (Api), a natural flavonoid, exerted antitumor effects against colon cancer both in vitro and in vivo with minimal toxicity. Multi-omics profiling revealed that Api coordinately disrupted central carbon metabolism and proliferation-related pathways. Mechanistically, Api treatment in HCT-116 cells suppressed the expression of pyruvate kinase M2 (PKM2), markedly inhibited lactate production, decreased adenosine triphosphate (ATP) generation rates from both glycolysis and oxidative phosphorylation, and dissipated mitochondrial membrane potential, collectively inducing a profound bioenergetic crisis. This metabolic collapse was accompanied by robust apoptosis, evidenced by increased apoptotic cells and cleavage of PARP‑1 and caspase‑3. Crucially, PKM2 overexpression attenuated Api-induced metabolic suppression, cytotoxicity, and apoptotic marker accumulation, establishing PKM2 as a key functional target. Our findings establish PKM2 as a key functional target in Api-induced energy crisis and apoptosis, underscoring its potential as a low-toxicity therapy for colon cancer.</p>","PeriodicalId":73042,"journal":{"name":"Food frontiers","volume":"7 4","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/fft2.70294","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148174218","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":"Antifungal Potential of Cumin Spice Seeds, Cuminum cyminum, Against Aspergillus fumigatus: Mechanistic Insights Into Ergosterol, Melanin, and Biofilm Inhibition","authors":"Acharya Balkrishna, Lovely Gupta, Rani Singh, Yash Varshney, Rishabh Dev, Pardeep Nain, Savita Lochab, Anurag Varshney","doi":"10.1002/fft2.70309","DOIUrl":"https://doi.org/10.1002/fft2.70309","url":null,"abstract":"<p>Spices are aromatic culinary ingredients used worldwide for enhancing food flavors, folklore therapy, and their antiseptic, antimicrobial properties. The present study investigated the antifungal effects and underlying mechanism of supercritical-fluid-extracted-oil from cumin (<i>Cuminum cyminum</i>) seeds (CcSO, hereafter) against pathogenic <i>Aspergillus fumigatus</i>. Listed in WHO-Fungal Priority Pathogens List, drug-resistant <i>A. fumigatus</i> infections carry high mortality rates, with limited therapeutic options. Antifungal resistance in <i>A. fumigatus</i> is largely attributed to genetic mutations, upregulated efflux pumps, and resilient biofilms. Chemical profiling of CcSO with GC-MS/MS and headspace-GC-FID identified five major phytoconstituents, namely β-pinene, p-cymene, γ-terpinene, cuminaldehyde, and 1,4-p-menthadien-7-al. At effective concentrations (0.7–1.5 mg/mL) against <i>A. fumigatus</i>, CcSO significantly suppressed fungal biomass and DHN-melanin biosynthesis by downregulating the <i>PksP</i> gene, and reduced total ergosterol content, accompanied by the downregulation of <i>Erg1</i>, <i>Erg4</i>, <i>Erg6</i>, and <i>SrbA</i> genes. Additionally, the downregulation of hyphal catalase <i>Cat2</i> gene with CcSO treatment indicated the generation of oxidative stress. <i>Aspergillus fumigatus</i> treated with CcSO demonstrated deformed conidia, impaired hyphal growth, and delayed germination in a time- and dose-dependent manner. CcSO prevented <i>A. fumigatus</i> biofilm formation and eradicated the pre-formed biofilms. The current study experimentally demonstrates fungicidal activity of CsSO vapors. Notably, this vapor phase-mediated anti-aspergillus effect of CcSO was predominantly driven by cuminaldehyde that suppressed <i>A. fumigatus</i> growth without being in direct contact. Amid the global concern of antifungal resistance, combining direct (contact-based) treatment with volatile oil therapy represents a promising natural reservoir of antifungal agents that could combat the antifungal resistance and address unmet medical needs.</p>","PeriodicalId":73042,"journal":{"name":"Food frontiers","volume":"7 4","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/fft2.70309","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148174217","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}
Food frontiersPub Date : 2026-06-04DOI: 10.1002/fft2.70312
Zhenlin Han, Tian Ye, Yantian Tang, Guodong Su, Jiazhou Li, Ningyang Li
{"title":"Alliinase: A Comprehensive Review of the Pivotal Enzyme in Garlic Chemistry and Its Applications","authors":"Zhenlin Han, Tian Ye, Yantian Tang, Guodong Su, Jiazhou Li, Ningyang Li","doi":"10.1002/fft2.70312","DOIUrl":"https://doi.org/10.1002/fft2.70312","url":null,"abstract":"<p>Alliinase is a pyridoxal 5′-phosphate (PLP)-dependent lyase that serves as the cornerstone of the defense system in plants of the <i>Allium</i> genus such as garlic. Upon tissue damage, this pivotal enzyme catalyzes the hydrolysis of odorless, nonvolatile <i>S</i>-alk(en)yl-<span>l</span>-cysteine sulfoxides (e.g., alliin) into volatile, bioactive organosulfur compounds, most notably allicin, which is responsible for garlic's distinctive aroma and its wide-ranging medicinal properties, including antimicrobial and antioxidant effects. This review comprehensively summarizes the current knowledge on the enzyme's discovery, molecular structure, biochemical properties including substrate specificity, pH/thermal stability, and sensitivity to metal ions, three-dimensional structure, reaction mechanism, genetic regulation, isolation, and immobilization. Harnessing alliinase extracted directly from garlic is significantly challenged by its low yield and inherent instability. To address these limitations, this review details recent advances in enhancing enzyme availability through heterologous expression and improving operational stability via immobilization on various supports, such as chitosan, alginate, and synthetic polymers. Furthermore, it explores the broad applications of alliinase across the food, pharmaceutical, and biotechnology industries, particularly in the production of allicin and related bioactive compounds. Finally, the review outlines future research directions, emphasizing the potential of protein engineering, advanced expression systems, and novel immobilization strategies to fully unlock the industrial potential of this versatile enzyme.</p>","PeriodicalId":73042,"journal":{"name":"Food frontiers","volume":"7 4","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/fft2.70312","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148174216","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":"High-Carbohydrate Diet Enhances Peripheral Nerve Regeneration via Hemoglobin Upregulation in Schwann Cells","authors":"Shiying Li, Dong Liu, Lin Yu, Yuanyuan Chen, Fuqian Zhang, Xuchao Yan, Yang Qian, Mingwen Zhang, Tianling Song, Jing Zhang, Guifang Wang, Xin Wang, Chunhong Xue, Chen Chen, Guowei Le, Caiping Wang, Dandan Chu","doi":"10.1002/fft2.70307","DOIUrl":"https://doi.org/10.1002/fft2.70307","url":null,"abstract":"<p>Motor dysfunction resulting from peripheral nerve injury significantly impacts quality of life. Nutritional support is a crucial complementary therapy, yet the specific roles of the three primary macronutrients—carbohydrates, proteins, and fats—in peripheral nerve regeneration remain unclear. This study systematically examined the effects of short-term and long-term high-fat, high-protein, and high-carbohydrate diets on regeneration following sciatic nerve injury in mice. Our findings revealed that a short-term high-carbohydrate diet markedly enhanced gait restoration, improved nerve conduction velocity, stimulated axonal regrowth, and promoted Schwann cell proliferation and migration, leading to an increased number of myelin layers. In contrast, short-term high-fat, long-term high-carbohydrate, and long-term high-protein diets provided only moderate benefits, while short-term high-protein and long-term high-fat diets demonstrated minimal effects. Transcriptome sequencing of the injured sciatic nerves indicated significant upregulation of genes related to hemoglobin synthesis in the short-term high-carbohydrate group. Immunofluorescence staining confirmed elevated expression of Hba and Hbb in Schwann cells. Additionally, experiments with the Schwann cell line RSC96 demonstrated that overexpression of Hba-a1 and Hbb-bs significantly enhanced both proliferation and migration. These results suggest that a high-carbohydrate diet supports peripheral nerve regeneration by upregulating hemoglobin expression in Schwann cells, thus promoting their proliferation and migration to create a conducive microenvironment for repair. This study highlights that short-term high carbohydrate intake, as opposed to high protein or fat, is effective in promoting recovery following peripheral nerve injury, providing a new scientific basis for nutritional support during rehabilitation.</p>","PeriodicalId":73042,"journal":{"name":"Food frontiers","volume":"7 4","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/fft2.70307","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148099524","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}
Food frontiersPub Date : 2026-05-29DOI: 10.1002/fft2.70303
Yadi Qin, Jie Qian, Jian Sun, Qinqin Li, Jun Yao, Minwei Zhang
{"title":"Deep Learning Sensing Platform for Simultaneous Detection of Kanamycin and Kanamycin B Based on Dual-Recognition and Catalytic Modulation Mechanism of Aptamer-Functionalized MIL-101 Nanozyme","authors":"Yadi Qin, Jie Qian, Jian Sun, Qinqin Li, Jun Yao, Minwei Zhang","doi":"10.1002/fft2.70303","DOIUrl":"https://doi.org/10.1002/fft2.70303","url":null,"abstract":"<p>Extensive antibiotic use has raised concerns over residues in food, necessitating rapid and accurate detection. This study integrates smartphone-assisted deep learning with aptamer-functionalized MIL-101(Fe) nanozymes to build a dual-recognition biosensor capable of simultaneously identifying and quantifying kanamycin (KAN) and kanamycin B (KMB). MIL-101(Fe) exhibited strong adsorption energies and high Langmuir-fitted capacities (28.39 mg/g for KAN; 31.36 mg/g for KMB), indicating monolayer binding at Fe─OH sites that partially suppressed catalytic activity. Aptamer modification enabled selective molecular recognition and accelerated electron transfer, synergistically enhancing nanozyme performance. Coupled with a ResNet-based multitask model, smartphone imaging achieved accurate classification of single and mixed samples and precise quantification over 5–1000 nM. Tests in honey and beef showed recoveries of 84.71%–111.50%, confirming stability and practicality. Overall, the aptamer-enhanced MIL-101(Fe) nanozyme combined with deep learning provides a sensitive, portable approach for on-site monitoring of antibiotic residues in food.</p>","PeriodicalId":73042,"journal":{"name":"Food frontiers","volume":"7 4","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/fft2.70303","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148098048","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":"Scutellarein Alleviates Ulcerative Colitis by Reshaping Gut Microbiota and Regulating the PRMT1-Mediated Th17/Treg Balance","authors":"Yefan Zhou, Xinyu Xu, Huan Fang, Xue Wang, Jiaqi Hua, Linping Lu, Dongxu Li, Yangyang Wen, Jieqiong Yao, Fang Liu, Jing He, Fucheng He, Mingxia Zhou","doi":"10.1002/fft2.70301","DOIUrl":"https://doi.org/10.1002/fft2.70301","url":null,"abstract":"<p>Ulcerative colitis (UC) is a chronic inflammatory disease of the colonic mucosa with an increasing global burden and limited therapeutic efficacy. Scutellarein (Scu), a bioactive flavonoid found in various edible plants of <i>Lamiaceae</i> and <i>Verbenaceae</i>, has been shown to possess anti-inflammatory and antioxidant activities. Herein, we systematically evaluated the effectiveness of scutellarein in the treatment of UC and identified its direct target and underlying inflammation suppression mechanism. Integrated 16S rRNA sequencing and untargeted metabolomics showed that scutellarein preserves gut microbial and metabolic homeostasis and enhances intestinal barrier integrity via enrichment of D-(-)-quinic acid (DQ). Limited proteolysis mass spectrometry (Lip-MS) identified protein arginine methyltransferase 1 (PRMT1) as a bona fide target of scutellarein. Mechanistic investigations further uncovered that scutellarein directly binds to the Y128 residue of PRMT1, which in turn inhibits STAT3 asymmetric dimethylation and phosphorylation. This cascade collectively downregulates RORγt expression, restrains Th17 differentiation, and ultimately restores the Th17/Treg cell equilibrium. Overall, scutellarein exerts dual protective effects in UC by reinforcing epithelial barrier function through microbiota-metabolite regulation and suppressing mucosal inflammation via the PRMT1/STAT3/RORγt axis. Our findings not only elucidate a novel multicomponent mechanism for a natural product but also nominate PRMT1 as a compelling new therapeutic target for UC.</p>","PeriodicalId":73042,"journal":{"name":"Food frontiers","volume":"7 4","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/fft2.70301","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148098292","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}