Food & Function最新文献

{"title":"Daphnetin attenuates the early stage of adipogenesis <i>via</i> suppressing mitotic clonal expansion through Nrf2-mediated redox regulation.","authors":"Xiao Chen Shi, Ying Zhang, Yu Tong Wang, Yun Feng Liu, Yi Zhang, Ai Jin","doi":"10.1039/d6fo03104h","DOIUrl":"10.1039/d6fo03104h","url":null,"abstract":"<p><p>Obesity is a major metabolic disorder closely associated with redox imbalance and excessive adipose tissue expansion, yet safe and effective natural compounds targeting early adipogenic events remain limited. Daphnetin, a naturally occurring coumarin derived from edible plants with reported antioxidant properties, has not been fully characterized in the context of adipocyte differentiation and obesity development. Here, we demonstrate that daphnetin significantly attenuates both diet-induced and genetically induced obesity in mice, as evidenced by reduced adiposity and improved glucose homeostasis, without affecting food intake or inducing detectable toxicity. Mechanistically, daphnetin suppresses adipogenesis by targeting mitotic clonal expansion (MCE), a critical early stage of adipocyte commitment. Further investigation revealed that daphnetin effectively modulates intracellular redox homeostasis by reducing reactive oxygen species (ROS) accumulation and promoting nuclear translocation of Nrf2 during adipocyte differentiation. Restoration of oxidative stress by exogenous H₂O₂ abolished the inhibitory effects of daphnetin on MCE and adipogenesis. Consistently, genetic knockdown or pharmacological inhibition of Nrf2 reversed daphnetin-mediated antioxidant signaling and rescued adipogenic progression. Collectively, these findings identify a previously unrecognized Nrf2-ROS-MCE regulatory axis as a key target of daphnetin in adipocyte biology. This study highlights early-stage redox modulation by natural dietary-derived compounds as a promising strategy for preventing obesity and associated metabolic disorders.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":"9192-9205"},"PeriodicalIF":6.3,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101276","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":"Effects of repetitive pretreatment with isothiocyanates on the stress resistance capacity of RGM1 cells.","authors":"Manami Takeyasu, Shiho Kawaguchi, Akari Ishisaka, Akira Murakami","doi":"10.1039/d6fo02569b","DOIUrl":"10.1039/d6fo02569b","url":null,"abstract":"<p><p>In this study, we investigated the effects of repeated isothiocyanate (ITC) pretreatment on cytotoxicity, cytoprotective gene expression, and chromatin accessibility in rat gastric epithelial RGM1 cells. Cells were pretreated with ITCs at low concentrations (0-2 µM) four times at 48 h intervals, followed by exposure to higher concentrations of ITCs. Repeated benzyl isothiocyanate (BITC) pretreatment significantly attenuated BITC-induced cytotoxicity compared with untreated controls. Moreover, repeated BITC pretreatment (2 µM) markedly increased the mRNA expression levels of cytoprotective genes, including glutathione <i>S</i>-transferase π and heat shock protein 27. Repeated BITC pretreatment also conferred cross-tolerance to low-pH and heat stress conditions. In addition, BITC treatment significantly upregulated the expression of several carbonic anhydrase isoforms associated with intracellular pH homeostasis. A DNase I-based chromatin accessibility assay revealed that repeated BITC pretreatment promoted euchromatin formation at the HO-1 gene locus. Furthermore, euchromatin formation in cytoprotective gene regions was also induced under various stress conditions. These findings suggest that repeated exposure to BITC enhances cellular stress tolerance through the induction of cytoprotective genes and stress-dependent chromatin remodeling.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":"9222-9233"},"PeriodicalIF":6.3,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101270","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":"<i>Citri reticulatae pericarpium viride</i> attenuates metabolic dysfunction-associated steatotic liver disease by activating PGC-1α-mediated fatty acid oxidation in mice.","authors":"Ting Hu, Ming Zhou, Wen Jiang, Chen Ye, Lijuan Sun, Jichao Liang, Yong Chen","doi":"10.1039/d6fo02111e","DOIUrl":"10.1039/d6fo02111e","url":null,"abstract":"<p><p><i>Citri reticulatae pericarpium viride</i>, a fruit peel from immature <i>Citrus reticulata</i> Blanco known as Qing Pi (QP) in Chinese, is a traditional food ingredient widely employed for culinary flavoring and aroma enhancement. Although QP exerts various metabolic benefits, the impacts and mechanisms of QP on preventing metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear. Here, we found that QP extracts (extracted with 75% concentrated ethanol and ethyl acetate) not only decreased high-fat diet (HFD)-induced hepatic triglyceride accumulation and oxidative damage, ameliorated glucose intolerance and enhanced insulin sensitivity after oral administration in mice, but also inhibited free fatty acid-induced steatosis and oxidative stress in QP extract-treated primary mouse hepatocytes. Furthermore, we profiled the absorbed components in the serum of mice by UHPLC-Orbitrap MS after oral gavage of QP extracts, and a total of fifteen flavonoid components were identified. By integrating the results of network pharmacology, molecular docking and transcriptomic sequencing, we analyzed the mechanism of action of QP extracts and found that the PGC-1α-PPARα axis and fatty acid oxidation pathway were highly enriched. QP treatment increased fatty acid oxidation (FAO) and the protein expression of p-AMPK, PGC-1α and PPARα, along with increased mRNA expression of key CYP450 enzymes involved in FAO. Pharmacological inhibition of AMPK or PPARα partially abrogated these effects. Therefore, our results highlight QP's potential as a functional food for the management of MASLD.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":"9307-9322"},"PeriodicalIF":6.3,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101190","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":"Gastric lipase and PLRP2 trigger the activity of pancreatic lipase on various emulsions stabilized by phospholipids or galactolipids.","authors":"Carolina Quezada, Elizabeth Troncoso, Hélène Launay, Frédéric Carrière","doi":"10.1039/d6fo03954e","DOIUrl":"https://doi.org/10.1039/d6fo03954e","url":null,"abstract":"<p><p>Dietary lipids are often consumed as oil-in-water emulsions, in which the interfacial structure governs enzyme accessibility and lipid digestion. This study investigated how the prior action of gastric lipase (GL) or pancreatic lipase-related protein 2 (PLRP2) modulates the subsequent activity of pancreatic lipase (PL) and triacylglycerol (TAG) hydrolysis. O/W emulsions of linseed oil stabilized with phosphatidylcholine (PC) or galactolipids (digalactosyldiacylglycerol, DGDG) were compared with Intralipid® and fresh bovine milk as reference substrates. Real time continuous assay of free fatty acid (FFA) release by the pHstat technique allowed determining kinetic parameters (initial and maximum (<i>V</i>_max) lipolysis rates; lag time, <i>τ</i>) of emulsion lipolysis by pancreatic lipase (PL; either from porcine pancreatic extracts or purified human pancreatic lipase and colipase), following preincubation with either recombinant dog gastric lipase (rDGL, pH 5.0) or guinea pig PLRP2 (GPLRP2, pH 8.0). Regardless of the type of emulsion, PL, showed a weak activity only revealed after long <i>τ</i>. Preincubation with rDGL or GPLRP2 markedly enhanced lipolysis by PL and reduced or suppressed lag times for reaching <i>V</i>_max. These findings show that the PL activity is not intrinsically limited by polar lipids at the interface, but dynamically regulated by prior interfacial conditioning. A mechanistic basis for the synergistic and sequential action of lipases is proposed, involving either a direct action of GL on TAG through its penetration of the interfacial layer or the digestion of DGDG or PC by PLRP2, both resulting in the production of FFAs facilitating PL-colipase adsorption. Early lipolysis events thus emerge as key determinants of lipid digestion.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190256","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":"Eugenol alleviates dityrosine-triggered insulin resistance and LPS-related inflammatory response by modulating gut microbiota homeostasis.","authors":"Jia Chen, Jingnan Zhu, Qin Jia, Tianyuan Song, Zhenyu Gu, Hongyun Wang, Yin-Yi Ding","doi":"10.1039/d6fo02007k","DOIUrl":"https://doi.org/10.1039/d6fo02007k","url":null,"abstract":"<p><p>Insulin resistance (IR) is a key pathological basis of metabolic diseases. Dityrosine (Dityr), a characteristic protein oxidation product commonly present in over-processed foods, can induce IR by disrupting metabolic homeostasis. Eugenol (EUG), a natural phenolic compound with anti-inflammatory and antioxidant activities, has been shown to improve insulin sensitivity. However, its protective effect and underlying mechanism against Dityr-induced IR remain unclear. The present study aimed to investigate the effect of EUG on Dityr-induced IR in C57BL/6 mice and explore its potential mechanisms. As a result, EUG significantly improved glucose metabolism and lipid metabolism in Dityr-exposed mice in a dose-dependent manner. This study also suggested that EUG effectively decreased the levels of lipopolysaccharide (LPS), LPS-binding protein (LBP), Toll-like receptor 4 (TLR4), nuclear factor kappa B (NFκB), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) and increased the level of interleukin-10 (IL-10) in Dityr-exposed mice. EUG alleviated oxidative stress induced by Dityr and upregulated the expression of the Nrf2/ARE signaling pathway. Importantly, <i>in vivo</i> animal experiments suggested that EUG reshaped the gut microbiota in Dityr-exposed mice at the phylum level, thereby reducing gut microbiota-derived LPS secretion and LPS-related inflammatory response. In conclusion, the effects of EUG on IR and the activation of LPS-related inflammatory response in Dityr-exposed mice might be attributed to the reconstruction of gut microbiota structure.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190267","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":"Homologous ginger-derived vesicle-like nanocarriers enhance the stability, gastrointestinal bioaccessibility, and macrophage anti-inflammatory activity of 6-gingerol.","authors":"Xiangyu Fu, Jingjing Fu, Yuanyue Jin, Xianrui Liang, Sheng Fang","doi":"10.1039/d6fo03003c","DOIUrl":"https://doi.org/10.1039/d6fo03003c","url":null,"abstract":"<p><p>The application of 6-gingerol (6-G) in functional foods is limited by its poor aqueous dispersibility, chemical instability, and low oral bioaccessibility. Herein, ginger-derived extracellular vesicle-like nanovesicles (GDEVs) were developed as homologous vesicular matrices for stabilizing and delivering 6-G. GDEVs-6-G was prepared using an ultrasonication-assisted method and exhibited high encapsulation efficiency (87.04%) and loading capacity (11.81%). Structural characterization showed that 6-G was incorporated into GDEVs mainly through non-covalent interactions without disrupting vesicle morphology. Compared with free 6-G, GDEVs-6-G showed improved resistance to heat, UV irradiation, pH variation, ionic strength, and storage at -80 °C, indicating enhanced processing and storage stability. During simulated gastrointestinal digestion, GDEVs-6-G showed a sustained release profile and increased the bioaccessibility of 6-G from 26.23% to 43.34%. In LPS-stimulated RAW264.7 macrophages, GDEVs-6-G exhibited good cytocompatibility, promoted cellular uptake, reduced intracellular ROS accumulation, and more effectively suppressed NO production and the expression of pro-inflammatory cytokines, including TNF-<i>α</i>, IL-1<i>β</i>, and IL-6, than free 6-G or blank GDEVs. These results demonstrate that GDEVs can act as homologous food-derived vesicular carriers to enhance the stability, gastrointestinal bioaccessibility, and macrophage-level antioxidant and anti-inflammatory functions of 6-G.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190211","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":"Dietary anthocyanins as multifunctional bioactives targeting obesity across experimental and clinical models.","authors":"Leila Amjad, Dinushi Gamage, H P Vasantha Rupasinghe","doi":"10.1039/d6fo02463g","DOIUrl":"https://doi.org/10.1039/d6fo02463g","url":null,"abstract":"<p><p>Obesity has emerged as a critical global health issue, contributing to cardiometabolic and other chronic diseases. Current management strategies, including diet, lifestyle modification, and pharmacotherapy, often lack sustainable efficacy and carry side effects. The search for safe, natural interventions has drawn attention to plant-based bioactives, particularly anthocyanins, which are abundant in dark-pigmented fruits and exhibit antioxidant and anti-obesogenic effects. This review critically evaluates the anti-obesogenic potential of anthocyanins, drawing on <i>in vitro</i>, preclinical, and clinical studies. Preclinical evidence demonstrates that anthocyanins improve lipid and glycemic profiles and insulin sensitivity, while reducing body weight, adiposity, hepatic steatosis, and systemic inflammation. Clinical trials generally support beneficial effects of anthocyanin-rich foods and supplements on selected cardiometabolic parameters (<i>e.g.</i>, lipids, glycemic control, and inflammation) in individuals with overweight or obesity, while effects on body weight and adiposity are modest or inconsistent. Mechanistically, anthocyanins inhibit pancreatic lipase, adipogenesis, and lipogenesis; promote fatty acid β-oxidation through AMP-activated protein kinase (AMPK) driven peroxisome proliferator-activated receptor alpha (PPARα) signaling; enhance thermogenesis <i>via</i> upregulation of uncoupling protein 1 (UCP1) and PR domain-containing 16 (PRDM16); and stimulate mitochondrial biogenesis in adipose tissue. In addition, anthocyanins attenuate oxidative stress and chronic inflammation by reducing reactive oxygen species, pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and by modulating nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Furthermore, anthocyanins beneficially modulate the gut microbiota, enriching species such as <i>Akkermansia muciniphila</i>, increasing short-chain fatty acid production, and improving intestinal barrier integrity. Overall, anthocyanins represent a compelling, multi-targeted natural intervention for obesity and its metabolic complications. These natural strategies may complement established pharmacotherapies and, when embedded in plant-forward dietary patterns and sustainable food systems, contribute to a more holistic approach to planetary health.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190285","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":"Effects of locust bean gum on cholesterol gallstones and the gut microbiota in lithogenic diet-fed C57BL/6J mice.","authors":"Xinke Liu, Jianing Zhang, Sa Zhou, Xuegang Luo, Yajian Song","doi":"10.1039/d6fo03327j","DOIUrl":"https://doi.org/10.1039/d6fo03327j","url":null,"abstract":"<p><p>Locust bean gum (LBG) is widely used as a thickener, stabilizer, emulsifier, and gelling agent in the food industry. In this study, a lithogenic diet-induced mouse model of cholesterol gallstones was employed to examine the effects of dietary supplementation with 2% and 5% LBG. Compared to the 5% dose, the 2% dose demonstrated superior efficacy. Gut microbiota analysis revealed that the lithogenic diet disrupted the network formed by Bacillota and Bacteroidota. Intervention with 2% LBG increased the abundance of Bacillota and established a network dominated by this phylum, accompanied by the enrichment of functional genes related to two-component systems, quorum sensing and biofilm formation. In contrast, 5% LBG failed to restore the intestinal network and only elevated the abundance of certain specific members. Furthermore, 2% LBG significantly reduced the abundance of <i>Desulfovibrio</i> and the expression of genes involved in H₂S synthesis, while also promoting a more pronounced increase in butyrate levels. Both 2% and 5% LBG suppressed HMGCR gene expression. Additionally, 2% LBG significantly downregulated the transcription of ABCG5/G8 genes and upregulated that of CYP7A1 and CYP8B1 genes, thereby decreasing cholesterol synthesis and secretion and enhancing its conversion into bile acids. Collectively, these results led to marked alterations in bile acid profiles across the groups, and consequently influenced the degree of gallstone formation. This study demonstrates for the first time that LBG dose-dependently protects mice against lithogenic diet-induced cholesterol gallstones and provides mechanistic insights into its protective effects.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190283","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":"Prebiotic potential and modulation of the fecal microbiota by konjac oligo-glucomannan prepared using <i>Pediococcus acidilactici</i> mannanase.","authors":"Shuhan Yang, Xi Chen, Zijing Li, Ruoxi Yang, Dan Zhao","doi":"10.1039/d6fo02824a","DOIUrl":"https://doi.org/10.1039/d6fo02824a","url":null,"abstract":"<p><p>In this study, konjac oligo-glucomannan (KOGM) was prepared from konjac glucomannan (KGM) by enzymatic hydrolysis using β-mannanase derived from <i>Pediococcus acidilactici</i> HDM2. The prepared KOGM had an average molecular weight of 13.4 kDa under optimized conditions (50 °C, pH 6.0, 80 U mL^-1 and 180 min). The KOGM exhibited selective prebiotic potential by promoting probiotic growth, particularly <i>Lacticaseibacillus paracasei</i> HD1.7 and <i>Lactiplantibacillus plantarum</i> CICC 6076. In contrast, it inhibited the growth of potentially harmful bacteria, including <i>Klebsiella pneumoniae</i> and <i>Enterobacter</i> spp. Its prebiotic potential was further evaluated using an <i>in vitro</i> fecal fermentation model with six treatment groups: blank control, commercial mannan oligosaccharides (MOS), KGM, KOGM, KGM combined with HDM2 (KGM2), and KOGM combined with HDM2 (KOGM2). After 24 h of fermentation, the KOGM2 group exhibited the lowest pH (3.89 ± 0.03, <i>P</i> < 0.05) and increased production of short-chain fatty acids (SCFAs), particularly acetate (2062.72 μg mL^-1), propionate (1356.81 μg mL^-1), and valerate (16.89 μg mL^-1). Notably, the KGM2 group produced the highest acetate level, while KGM yielded the greatest butyrate content (206.7 ± 15.0 μg mL^-1). α and β diversity analyses revealed that KGM and KOGM treatments enhanced microbial diversity and accelerated community stabilization. Furthermore, KOGM enriched beneficial phyla such as Bacteroidetes and Actinobacteria, stimulated the growth of beneficial genera including <i>Bifidobacterium</i>, <i>Prevotella</i>, and <i>Limosilactobacillus</i>, and reduced potential pathogens including <i>Escherichia</i>-<i>Shigella</i> and Proteobacteria. These findings highlight the prebiotic potential of enzymatically prepared KOGM, which effectively modulates gut microbiota composition and promotes beneficial metabolic activity.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178023","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":"Recombinant bovine αs1-casein ameliorates PCPA-induced insomnia-like behavioral and physiological abnormalities in mice.","authors":"Xiang-Li Mu, Yan Sun, Meng-Jia Song, Lin-Lin Ding, Jing-Yang Cai, Ai-Mei Liao, Yin-Chen Hou, Ji-Hong Huang, Guang-Hai Yu, Long Pan","doi":"10.1039/d6fo03828j","DOIUrl":"https://doi.org/10.1039/d6fo03828j","url":null,"abstract":"<p><p>Insomnia is a multifactorial sleep-wake disorder associated with altered neurotransmitter homeostasis, systemic inflammatory changes, and gut microbial dysbiosis. Recombinant bovine αs1-casein (RC) is a scalable milk-protein ingredient, but its effects on insomnia-like physiological and behavioral abnormalities have not been systematically evaluated. We investigated RC in a <i>p</i>-chlorophenylalanine (PCPA)-induced mouse model. Male ICR mice received RC (100, 300, or 500 mg kg^-1 day^-1), melatonin, Naoxinshu oral liquid, natural casein, or vehicle for 7 days after PCPA modeling. Body weight, open-field behavior, serum cytokines, brain neurotransmitters, hippocampal histology, organ indices, and cecal microbiota were assessed. RC improved body-weight recovery and open-field performance without altering major-organ indices. It increased brain 5-HT, 5-HIAA, dopamine, GABA, and glutamate concentrations and reduced the elevated norepinephrine concentration. High-dose RC reduced serum IL-6 and was associated with better-preserved hippocampal morphology. 16S rRNA gene sequencing showed RC-associated changes in bacterial richness and community structure. The parallel physiological, neurochemical, inflammatory, and microbial changes support an association between RC administration and improvement of PCPA-induced insomnia-like abnormalities. These results identify recombinant bovine αs1-casein as a promising food-derived ingredient for further investigation in sleep-health applications, while the microbiota-gut-brain axis is presented as a testable mechanistic framework rather than a demonstrated causal pathway.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190209","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}