Shanli Zhang, Ziwei Huang, Xinhong Wang, Xiaowei Lu, Qingfeng Xie, Ziren Su, Jianhui Xie, Jiannan Chen and Liping Chen
Ergosterol and β-sitosterol are dietary sterols with cholesterol-lowering effects. They lower cholesterol by regulating cholesterol absorption and metabolism in the intestine and liver. Due to the low intestinal absorption rate of ergosterol and β-sitosterol, gut microbiota may play a key role in their anti-hypercholesterolemic effects. However, the precise mechanisms by which ergosterol and β-sitosterol modulate cholesterol absorption and metabolism via gut microbiota remain unclear. This study aims to investigate the relationship between the cholesterol-lowering effect of ergosterol and β-sitosterol and their regulation of gut microbiota. The results indicated that ergosterol and β-sitosterol promoted the excretion of cholesterol and bile acids and inhibited intestinal cholesterol absorption in hypercholesterolemic mice. They increased the intestinal proportion of Firmicutes and Clostridium to inhibit small intestinal FXR activity and activate hepatic FXR activity, consequently regulating the expression of bile acid transporters. Moreover, ergosterol and β-sitosterol elevated the cholesterol sulfate levels in the large intestine, which was linked to an increased proportion of Bacteroidia in the gut. Further experiments using the intestinal pseudo-sterility model revealed that the aforementioned effects of ergosterol and β-sitosterol depend on the presence of intestinal microbiota. The findings of this study provide novel insights into the cholesterol-lowering mechanism of ergosterol and β-sitosterol: they enhance cholesterol sulfonation and total bile acid excretion mediated by gut microbiota.
{"title":"Ergosterol and β-sitosterol exert cholesterol-lowering effects by enhancing gut microbiota-mediated cholesterol sulfonation and total bile acid excretion in mice","authors":"Shanli Zhang, Ziwei Huang, Xinhong Wang, Xiaowei Lu, Qingfeng Xie, Ziren Su, Jianhui Xie, Jiannan Chen and Liping Chen","doi":"10.1039/D5FO03052H","DOIUrl":"10.1039/D5FO03052H","url":null,"abstract":"<p >Ergosterol and β-sitosterol are dietary sterols with cholesterol-lowering effects. They lower cholesterol by regulating cholesterol absorption and metabolism in the intestine and liver. Due to the low intestinal absorption rate of ergosterol and β-sitosterol, gut microbiota may play a key role in their anti-hypercholesterolemic effects. However, the precise mechanisms by which ergosterol and β-sitosterol modulate cholesterol absorption and metabolism <em>via</em> gut microbiota remain unclear. This study aims to investigate the relationship between the cholesterol-lowering effect of ergosterol and β-sitosterol and their regulation of gut microbiota. The results indicated that ergosterol and β-sitosterol promoted the excretion of cholesterol and bile acids and inhibited intestinal cholesterol absorption in hypercholesterolemic mice. They increased the intestinal proportion of Firmicutes and <em>Clostridium</em> to inhibit small intestinal FXR activity and activate hepatic FXR activity, consequently regulating the expression of bile acid transporters. Moreover, ergosterol and β-sitosterol elevated the cholesterol sulfate levels in the large intestine, which was linked to an increased proportion of <em>Bacteroidia</em> in the gut. Further experiments using the intestinal pseudo-sterility model revealed that the aforementioned effects of ergosterol and β-sitosterol depend on the presence of intestinal microbiota. The findings of this study provide novel insights into the cholesterol-lowering mechanism of ergosterol and β-sitosterol: they enhance cholesterol sulfonation and total bile acid excretion mediated by gut microbiota.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" 3","pages":" 1568-1587"},"PeriodicalIF":5.4,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146049559","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}
Adrià Vilalta, Maria Descamps-Solà, Marta Sierra-Cruz, Alba Miguéns-Gómez, Raúl Beltrán-Debón, Esther Rodríguez-Gallego, Montserrat Pinent, Maria Teresa Blay, Anna Ardévol and Ximena Terra
Ageing is associated with attenuated type-2 bitter-taste receptor (TAS2R) signalling and contributes to metabolic, inflammatory and barrier decline, but its system-wide impact along the gut remains undefined. We combined transcription analysis, physiology, metabolomics and microbiota profiling to test whether a brief grape-seed proanthocyanidin extract (GSPE) intervention can counter age-related dysfunction by long-term modulation of intestinal Tas2r expression. Female Wistar rats were distributed into young (2 months, n = 10) or aged (21 months, n = 24) groups; eleven aged animals received GSPE (500 mg kg−1, oral gavage) for 10 days, followed by a 75-day wash-out. After sacrifice, we quantified Tas2r mRNA in five gut segments, assessed ex vivo permeability, enteroendocrine outputs, systemic metabolites, inflammatory markers, 16S microbiota and the untargeted plasma metabolome. An elastic-net/PLS-DA/random-forest pipeline ranked variables discriminating age and GSPE effects, and GeneNet partial correlations generated an integrated network. Ageing suppressed Tas2r gene expression across the small intestine and the distal colon, while the proximal colon was largely unchanged. Despite the long wash-out, the brief GSPE treatment restored small-intestinal Tas2r transcription of some receptors while paradoxically down-regulating a subset in the distal colon. Consensus variable selection highlighted enterohormone expression and its ex vivo secretion, intestinal barrier dysfunction indices, some microbiota genera and several Tas2r transcripts among the 34 strongest discriminators. Tas2rs formed high-betweenness hubs linking epithelial integrity, inflammatory tone and butyrate-producing taxa. These findings indicate that intestinal type-2 bitter taste receptors (Tas2rs) may integrate multisystem regulatory networks fundamental to healthy ageing. Brief administration of grape-seed proanthocyanidin extract (GSPE) is sufficient to durably reprogramme Tas2r expression and the surrounding microbiota–endocrine–barrier landscape in aged rats.
{"title":"Linking intestinal bitter taste receptors and GSPE-induced long-lasting benefits in ageing rats: an integrative analysis","authors":"Adrià Vilalta, Maria Descamps-Solà, Marta Sierra-Cruz, Alba Miguéns-Gómez, Raúl Beltrán-Debón, Esther Rodríguez-Gallego, Montserrat Pinent, Maria Teresa Blay, Anna Ardévol and Ximena Terra","doi":"10.1039/D5FO03241E","DOIUrl":"10.1039/D5FO03241E","url":null,"abstract":"<p >Ageing is associated with attenuated type-2 bitter-taste receptor (TAS2R) signalling and contributes to metabolic, inflammatory and barrier decline, but its system-wide impact along the gut remains undefined. We combined transcription analysis, physiology, metabolomics and microbiota profiling to test whether a brief grape-seed proanthocyanidin extract (GSPE) intervention can counter age-related dysfunction by long-term modulation of intestinal <em>Tas2r</em> expression. Female Wistar rats were distributed into young (2 months, <em>n</em> = 10) or aged (21 months, <em>n</em> = 24) groups; eleven aged animals received GSPE (500 mg kg<small><sup>−1</sup></small>, oral gavage) for 10 days, followed by a 75-day wash-out. After sacrifice, we quantified Tas2r mRNA in five gut segments, assessed <em>ex vivo</em> permeability, enteroendocrine outputs, systemic metabolites, inflammatory markers, 16S microbiota and the untargeted plasma metabolome. An elastic-net/PLS-DA/random-forest pipeline ranked variables discriminating age and GSPE effects, and GeneNet partial correlations generated an integrated network. Ageing suppressed Tas2r gene expression across the small intestine and the distal colon, while the proximal colon was largely unchanged. Despite the long wash-out, the brief GSPE treatment restored small-intestinal Tas2r transcription of some receptors while paradoxically down-regulating a subset in the distal colon. Consensus variable selection highlighted enterohormone expression and its <em>ex vivo</em> secretion, intestinal barrier dysfunction indices, some microbiota genera and several Tas2r transcripts among the 34 strongest discriminators. Tas2rs formed high-betweenness hubs linking epithelial integrity, inflammatory tone and butyrate-producing taxa. These findings indicate that intestinal type-2 bitter taste receptors (Tas2rs) may integrate multisystem regulatory networks fundamental to healthy ageing. Brief administration of grape-seed proanthocyanidin extract (GSPE) is sufficient to durably reprogramme Tas2r expression and the surrounding microbiota–endocrine–barrier landscape in aged rats.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" 3","pages":" 1336-1349"},"PeriodicalIF":5.4,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/fo/d5fo03241e?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146058272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Correction for ‘Clinical and lipid metabolic responses to diacylglycerol oil administration in Chinese adults with overweight/obesity or central obesity: a randomized, double-blind, placebo-controlled trial’ by Liyuan Qin et al., Food Funct., 2026, https://doi.org/10.1039/D5FO02712H.
{"title":"Correction: Clinical and lipid metabolic responses to diacylglycerol oil administration in Chinese adults with overweight/obesity or central obesity: a randomized, double-blind, placebo-controlled trial","authors":"Liyuan Qin, Wei Zhao, Zhuohua Lin, Xin Bao, Rong Li, Qiyue Hao, Zhe Yi, Qun Shen, Hua Jiang, Yumei Zhang and Yong Xue","doi":"10.1039/D5FO90116B","DOIUrl":"10.1039/D5FO90116B","url":null,"abstract":"<p >Correction for ‘Clinical and lipid metabolic responses to diacylglycerol oil administration in Chinese adults with overweight/obesity or central obesity: a randomized, double-blind, placebo-controlled trial’ by Liyuan Qin <em>et al.</em>, <em>Food Funct.</em>, 2026, https://doi.org/10.1039/D5FO02712H.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" 2","pages":" 1093-1094"},"PeriodicalIF":5.4,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/fo/d5fo90116b?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145909566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stefano Quarta, Giuseppe Santarpino, Nadia Calabriso, Maria Annunziata Carluccio, Laura Siracusa, Tonia Strano, Francesco Cardetta, Luisa Siculella, Fabrizio Damiano, Raffaele De Caterina and Marika Massaro
Under proatherogenic conditions, epicardial (EAT) and pericardial adipose tissue (PAT) acquire inflammatory/pro-atherogenic phenotypes that contribute to coronary atherosclerosis. Recent data have highlighted a significant inverse relationship between levels of n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in adipose tissue and risk of myocardial infarction. Our study aimed at investigating whether DHA/EPA supplementation of cardiac fat adipocytes attenuates cardiac adipose tissue inflammation. To this aim mature adipocytes and adipose stem cells were isolated from PAT samples collected from coronary artery disease (CAD) patients undergoing coronary artery bypass grafting, exposed to DHA/EPA ex vivo, and evaluated for pro-inflammatory gene expression and activity. PAT adipocytes and stem cell exposure to DHA led to a significant increase in the membrane ratio of omega-3 to omega-6 PUFAs and decreased mRNA expression levels of monocyte chemoattractant protein (MCP)-1, interleukin(IL)-6, matrix metalloproteinase(MMP)-9 and CXC motif chemokine ligand (CXCL)10 (p < 0.05). This downregulation was accompanied by increased expression of uncoupling proteins (UCP)1 and 2 and heme-oxygenase (HO)-1 and of the anti-inflammatory and pro-resolving lipid mediator resolvin D1. Mechanistically, this protective modulation appears to be driven by the upregulation of peroxisome proliferator-activated receptor gamma (PPAR)-γ and nuclear factor erythroid 2-related factor (NRF)2, leading to increased NRF2 activity and suppressed NF-κB signaling. Functionally, supernatants from DHA-conditioned adipocytes exhibited reduced monocyte-attracting activity in chemotaxis assays. While EPA conditioning produced effects similar to DHA, arachidonic acid (AA) showed no significant biological effects. In conclusion, DHA and EPA mitigated the PAT inflammatory profile, highlighting the potential therapeutic role of such PUFAs in reducing cardiac adipose tissue inflammation. These results may have implications for treatment of CAD patients.
{"title":"Omega-3 PUFAs reduce inflammation by targeting NRF2 and NF-κB activity in an ex vivo model of cardiac mature adipocytes and adipose derived stem cells from atherosclerotic patients","authors":"Stefano Quarta, Giuseppe Santarpino, Nadia Calabriso, Maria Annunziata Carluccio, Laura Siracusa, Tonia Strano, Francesco Cardetta, Luisa Siculella, Fabrizio Damiano, Raffaele De Caterina and Marika Massaro","doi":"10.1039/D5FO03219A","DOIUrl":"10.1039/D5FO03219A","url":null,"abstract":"<p >Under proatherogenic conditions, epicardial (EAT) and pericardial adipose tissue (PAT) acquire inflammatory/pro-atherogenic phenotypes that contribute to coronary atherosclerosis. Recent data have highlighted a significant inverse relationship between levels of n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in adipose tissue and risk of myocardial infarction. Our study aimed at investigating whether DHA/EPA supplementation of cardiac fat adipocytes attenuates cardiac adipose tissue inflammation. To this aim mature adipocytes and adipose stem cells were isolated from PAT samples collected from coronary artery disease (CAD) patients undergoing coronary artery bypass grafting, exposed to DHA/EPA <em>ex vivo</em>, and evaluated for pro-inflammatory gene expression and activity. PAT adipocytes and stem cell exposure to DHA led to a significant increase in the membrane ratio of omega-3 to omega-6 PUFAs and decreased mRNA expression levels of monocyte chemoattractant protein (MCP)-1, interleukin(IL)-6, matrix metalloproteinase(MMP)-9 and CXC motif chemokine ligand (CXCL)10 (<em>p</em> < 0.05). This downregulation was accompanied by increased expression of uncoupling proteins (UCP)1 and 2 and heme-oxygenase (HO)-1 and of the anti-inflammatory and pro-resolving lipid mediator resolvin D1. Mechanistically, this protective modulation appears to be driven by the upregulation of peroxisome proliferator-activated receptor gamma (PPAR)-γ and nuclear factor erythroid 2-related factor (NRF)2, leading to increased NRF2 activity and suppressed NF-κB signaling. Functionally, supernatants from DHA-conditioned adipocytes exhibited reduced monocyte-attracting activity in chemotaxis assays. While EPA conditioning produced effects similar to DHA, arachidonic acid (AA) showed no significant biological effects. In conclusion, DHA and EPA mitigated the PAT inflammatory profile, highlighting the potential therapeutic role of such PUFAs in reducing cardiac adipose tissue inflammation. These results may have implications for treatment of CAD patients.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" 3","pages":" 1431-1450"},"PeriodicalIF":5.4,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/fo/d5fo03219a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145987386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaomei Wang, Jiao Yang, Jiayuan Zhang, Gaihong Yu, Jian Zhu and Yingli Nie
Given the potential of polyphenols to mitigate neurodegenerative diseases (NDDs), this meta-analysis investigated whether clinical evidence supports the use of polyphenols for neuroprotection and as nutritional strategies in NDDs. We analyzed different polyphenol types across seven NDDs, 13 studies involving 849 participants were included. Prespecified outcomes comprised global cognition (Mini-Mental State Examination, MMSE), domain-specific cognition (Alzheimer's Disease Cooperative Study–Cognitive Subscale, ADCS-Cog), activities of daily living (Alzheimer's Disease Cooperative Study–Activities of Daily Living, ADCS-ADL), neuropsychiatric symptoms (Neuropsychiatric Inventory, NPI), and selected biomarkers (plasma amyloid-β40 and brain-derived neurotrophic factor, BDNF). Reporting followed PRISMA 2020 guidelines, methods conformed to the Cochrane Handbook, and certainty of evidence was assessed using GRADE. Overall, polyphenol supplementation was associated with improved global cognition (pooled MD in MMSE = 2.06; 95% CI 0.62–3.49). In subgroup analyses, flavonoids were associated with a modest but significant improvement in MMSE scores, whereas stilbenes produced a significant benefit in daily functioning (ADCS-ADL) without clear gains in MMSE or ADCS-Cog and no consistent effects on NPI. Anthocyanidins, phenolic acids, and lignans did not significantly affect cognitive outcomes (MMSE or ADCS-Cog), and polyphenol subclasses did not yield robust or consistent changes in NPI or biomarker endpoints (Aβ40 and BDNF). Specific polyphenol subclasses therefore appear to confer selective cognitive and functional benefits, with stilbenes primarily supporting functional outcomes and flavonoids potentially enhancing global cognition.
考虑到多酚具有减轻神经退行性疾病(ndd)的潜力,本荟萃分析调查了临床证据是否支持在ndd中使用多酚作为神经保护和营养策略。我们分析了7个ndd中不同的多酚类型,包括13项研究,涉及849名参与者。预先指定的结果包括整体认知(迷你精神状态检查,MMSE)、特定领域认知(阿尔茨海默病合作研究-认知亚量表,ADCS-Cog)、日常生活活动(阿尔茨海默病合作研究-日常生活活动,ADCS-ADL)、神经精神症状(神经精神量表,NPI)和选定的生物标志物(血浆淀粉样蛋白-β40和脑源性神经营养因子,BDNF)。报告遵循PRISMA 2020指南,方法符合Cochrane手册,并使用GRADE评估证据的确定性。总体而言,多酚补充与整体认知改善相关(MMSE的汇总MD = 2.06; 95% CI 0.62-3.49)。在亚组分析中,黄酮类化合物与MMSE评分的适度但显著的改善有关,而芪在日常功能(ADCS-ADL)方面有显著的益处,但在MMSE或ADCS-Cog方面没有明显的提高,对NPI也没有一致的影响。花青素、酚酸和木酚素对认知结果没有显著影响(MMSE或ADCS-Cog),多酚亚类在NPI或生物标志物终点(Aβ40和BDNF)方面没有显著或一致的变化。因此,特定的多酚亚类似乎具有选择性的认知和功能益处,二苯乙烯主要支持功能结果,类黄酮可能增强整体认知。
{"title":"Polyphenol consumption and neurodegeneration risk: a systematic meta-analysis of randomized controlled trials bridging nutrition and cognitive health†","authors":"Xiaomei Wang, Jiao Yang, Jiayuan Zhang, Gaihong Yu, Jian Zhu and Yingli Nie","doi":"10.1039/D5FO05135E","DOIUrl":"10.1039/D5FO05135E","url":null,"abstract":"<p >Given the potential of polyphenols to mitigate neurodegenerative diseases (NDDs), this meta-analysis investigated whether clinical evidence supports the use of polyphenols for neuroprotection and as nutritional strategies in NDDs. We analyzed different polyphenol types across seven NDDs, 13 studies involving 849 participants were included. Prespecified outcomes comprised global cognition (Mini-Mental State Examination, MMSE), domain-specific cognition (Alzheimer's Disease Cooperative Study–Cognitive Subscale, ADCS-Cog), activities of daily living (Alzheimer's Disease Cooperative Study–Activities of Daily Living, ADCS-ADL), neuropsychiatric symptoms (Neuropsychiatric Inventory, NPI), and selected biomarkers (plasma amyloid-β40 and brain-derived neurotrophic factor, BDNF). Reporting followed PRISMA 2020 guidelines, methods conformed to the Cochrane Handbook, and certainty of evidence was assessed using GRADE. Overall, polyphenol supplementation was associated with improved global cognition (pooled MD in MMSE = 2.06; 95% CI 0.62–3.49). In subgroup analyses, flavonoids were associated with a modest but significant improvement in MMSE scores, whereas stilbenes produced a significant benefit in daily functioning (ADCS-ADL) without clear gains in MMSE or ADCS-Cog and no consistent effects on NPI. Anthocyanidins, phenolic acids, and lignans did not significantly affect cognitive outcomes (MMSE or ADCS-Cog), and polyphenol subclasses did not yield robust or consistent changes in NPI or biomarker endpoints (Aβ40 and BDNF). Specific polyphenol subclasses therefore appear to confer selective cognitive and functional benefits, with stilbenes primarily supporting functional outcomes and flavonoids potentially enhancing global cognition.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" 3","pages":" 1114-1126"},"PeriodicalIF":5.4,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/fo/d5fo05135e?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hsuan-Yin Chen, Chang-Lin Lin, Chou-Chen Chen and Jin-Yuarn Lin
Caffeic acid (CA) has been found to have the potential to inhibit the growth of human colorectal cancer HT-29 cells in vitro. However, the effects of CA administration on colorectal cancer growth and immunity in vivo remain unclear. To unravel the mystery of CA administration on cancer cell growth, serum antibody titers, lymphoid lineage cells in the peripheral blood, and the M1/M2 immune balance in BALB/c nude mice subcutaneously loaded with human colorectal cancer HT-29 cells for 35 days were examined in the experiment. The experimental mice were respectively given low (6 mg CA per kg AIN-93M feed), medium (30 mg CA per kg AIN-93M feed), and high (60 mg CA per kg AIN-93M feed) doses for 35 days. The results showed that CA administration tended to decrease the cancer cell volume and serum IgG and IgM levels compared to those in the dietary control (DC) group. CA administration slightly increased the proportion of CD3+ T and CD49+ natural killer cells, but decreased CD19+ B cells in the peripheral blood compared to those in the DC group, causing the immune cell distribution to be closer to the vehicle control (VC) group. The HT-29 cell-bearing mice exhibited an M2-polarized immune balance based on the TNF-α (M1)/IL-10 (M2) cytokine secretion ratio by macrophages compared to that in the VC group. Notably, low-dose CA administration significantly (P < 0.05) increased the TNF-α/IL-10 cytokine secretion ratio compared to that in the DC group, evidencing that low-dose CA administration reversed the immune response toward the M1-polarized immune balance in the HT-29 cell-bearing mice. CA administration may restore the M1-polarized immune balance but decrease serum IgG and IgM levels in subjects with colorectal cancer cells.
{"title":"Caffeic acid restores the M1-polarized immune balance but decreases IgG and IgM levels in human colorectal cancer HT-29 cell-bearing nude mice","authors":"Hsuan-Yin Chen, Chang-Lin Lin, Chou-Chen Chen and Jin-Yuarn Lin","doi":"10.1039/D5FO05024C","DOIUrl":"10.1039/D5FO05024C","url":null,"abstract":"<p >Caffeic acid (CA) has been found to have the potential to inhibit the growth of human colorectal cancer HT-29 cells <em>in vitro</em>. However, the effects of CA administration on colorectal cancer growth and immunity <em>in vivo</em> remain unclear. To unravel the mystery of CA administration on cancer cell growth, serum antibody titers, lymphoid lineage cells in the peripheral blood, and the M1/M2 immune balance in BALB/c nude mice subcutaneously loaded with human colorectal cancer HT-29 cells for 35 days were examined in the experiment. The experimental mice were respectively given low (6 mg CA per kg AIN-93M feed), medium (30 mg CA per kg AIN-93M feed), and high (60 mg CA per kg AIN-93M feed) doses for 35 days. The results showed that CA administration tended to decrease the cancer cell volume and serum IgG and IgM levels compared to those in the dietary control (DC) group. CA administration slightly increased the proportion of CD3<small><sup>+</sup></small> T and CD49<small><sup>+</sup></small> natural killer cells, but decreased CD19<small><sup>+</sup></small> B cells in the peripheral blood compared to those in the DC group, causing the immune cell distribution to be closer to the vehicle control (VC) group. The HT-29 cell-bearing mice exhibited an M2-polarized immune balance based on the TNF-α (M1)/IL-10 (M2) cytokine secretion ratio by macrophages compared to that in the VC group. Notably, low-dose CA administration significantly (<em>P</em> < 0.05) increased the TNF-α/IL-10 cytokine secretion ratio compared to that in the DC group, evidencing that low-dose CA administration reversed the immune response toward the M1-polarized immune balance in the HT-29 cell-bearing mice. CA administration may restore the M1-polarized immune balance but decrease serum IgG and IgM levels in subjects with colorectal cancer cells.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" 3","pages":" 1604-1619"},"PeriodicalIF":5.4,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146058237","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}
Fermented barley can be used as a functional ingredient of staple foods. In the present study, the effect of fermented barley bran addition on extruded rice was investigated in terms of digestive properties, gastrointestinal phenol release and antioxidant activities. Different nutrient compositions were observed between fermented barley extruded rice (FBER) and barley extruded rice (BER). After fermented barley bran addition, the resistant starch proportion increased to 17.49% and the glycemic index decreased to 68.82 in FBER. The release of phenols was more significant in FBER than in BER during digestion and colonic fermentation, leading to enhanced in vitro antioxidant activities. Among the phenolic compounds, ferulic acid exhibited different variation tendencies when comparing BER with FBER during colonic fermentation. According to the results of microbiota analysis, higher abundances of Lactobacillus and Bifidobacterium were observed in FBER-fermented faecal samples. Correlation network analysis further revealed the potential role of Megasphaera and Bifidobacterium in the biotransformation of specific phenols.
{"title":"Fermented barley bran addition improved the digestive properties, gastrointestinal phenol release and the antioxidant activities of extruded rice","authors":"Yufeng He, Mingzhe Chen, Yunxuan Tang, Wenxuan Tui, Qi Gan, Ying Zhu, Jiayan Zhang, Yansheng Zhao, Xiangping Zhang and Xiang Xiao","doi":"10.1039/D5FO05414A","DOIUrl":"10.1039/D5FO05414A","url":null,"abstract":"<p >Fermented barley can be used as a functional ingredient of staple foods. In the present study, the effect of fermented barley bran addition on extruded rice was investigated in terms of digestive properties, gastrointestinal phenol release and antioxidant activities. Different nutrient compositions were observed between fermented barley extruded rice (FBER) and barley extruded rice (BER). After fermented barley bran addition, the resistant starch proportion increased to 17.49% and the glycemic index decreased to 68.82 in FBER. The release of phenols was more significant in FBER than in BER during digestion and colonic fermentation, leading to enhanced <em>in vitro</em> antioxidant activities. Among the phenolic compounds, ferulic acid exhibited different variation tendencies when comparing BER with FBER during colonic fermentation. According to the results of microbiota analysis, higher abundances of <em>Lactobacillus</em> and <em>Bifidobacterium</em> were observed in FBER-fermented faecal samples. Correlation network analysis further revealed the potential role of <em>Megasphaera</em> and <em>Bifidobacterium</em> in the biotransformation of specific phenols.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" 3","pages":" 1277-1291"},"PeriodicalIF":5.4,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146058289","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}
Jun Gong, Xiuzhen Jia, Lei Wang, Yiwu Lu, Rui Guo, Ruihan Gong, Jingyu Hao, Zifu Zhao, Sufang Duan, Xuebo Liu, Jian He, Hongwei Li and Zhigang Liu
Chronic stress-induced sleep disorders are characterized by disrupted sleep architecture and a significant reduction in slow-wave sleep (SWS). These disorders represent a major public health challenge and are mechanistically linked to the hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis. This study employed a translational research paradigm-including zebrafish screening, a chronic unpredictable mild stress (CUMS) mouse model, and an eight-week randomized, placebo-controlled human trial-to evaluate the efficacy of a combination of walnut peptide and theanine (WPT). Treatment with WPT reduced waking activity and duration in pentylenetetrazole (PTZ)-induced zebrafish. In CUMS mice, the combination significantly improved sleep architecture by restoring the duration of SWS and enhanced sleep quality by increasing delta wave power density. Mechanistically, the intervention corrected hypothalamic-pituitary-adrenal (HPA) axis hyperactivity by lowering elevated serum corticosterone (CORT) levels. Furthermore, it modulated central neurotransmitters, notably reversing stress-induced deficits by increasing the levels of the inhibitory neurotransmitter GABA and tryptophan, a key precursor for serotonin and melatonin. In the human trial, the WPT restored sleep duration and improved subjective sleep quality scores (assessed by the Pittsburgh Sleep Quality Index, PSQI). In conclusion, this translational study provides robust evidence that the WPT effectively improves chronic stress-induced sleep disorders in zebrafish and mice, and improves sleep disturbances in adults (PSQI ≥ 7) by regulating HPA axis function and restoring the duration and quality of SWS. This makes it a highly promising nutritional intervention strategy.
{"title":"Walnut peptide and theanine combination ameliorates sleep disorders: a multi-species study including a human trial","authors":"Jun Gong, Xiuzhen Jia, Lei Wang, Yiwu Lu, Rui Guo, Ruihan Gong, Jingyu Hao, Zifu Zhao, Sufang Duan, Xuebo Liu, Jian He, Hongwei Li and Zhigang Liu","doi":"10.1039/D5FO03867G","DOIUrl":"10.1039/D5FO03867G","url":null,"abstract":"<p >Chronic stress-induced sleep disorders are characterized by disrupted sleep architecture and a significant reduction in slow-wave sleep (SWS). These disorders represent a major public health challenge and are mechanistically linked to the hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis. This study employed a translational research paradigm-including zebrafish screening, a chronic unpredictable mild stress (CUMS) mouse model, and an eight-week randomized, placebo-controlled human trial-to evaluate the efficacy of a combination of walnut peptide and theanine (WPT). Treatment with WPT reduced waking activity and duration in pentylenetetrazole (PTZ)-induced zebrafish. In CUMS mice, the combination significantly improved sleep architecture by restoring the duration of SWS and enhanced sleep quality by increasing delta wave power density. Mechanistically, the intervention corrected hypothalamic-pituitary-adrenal (HPA) axis hyperactivity by lowering elevated serum corticosterone (CORT) levels. Furthermore, it modulated central neurotransmitters, notably reversing stress-induced deficits by increasing the levels of the inhibitory neurotransmitter GABA and tryptophan, a key precursor for serotonin and melatonin. In the human trial, the WPT restored sleep duration and improved subjective sleep quality scores (assessed by the Pittsburgh Sleep Quality Index, PSQI). In conclusion, this translational study provides robust evidence that the WPT effectively improves chronic stress-induced sleep disorders in zebrafish and mice, and improves sleep disturbances in adults (PSQI ≥ 7) by regulating HPA axis function and restoring the duration and quality of SWS. This makes it a highly promising nutritional intervention strategy.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" 3","pages":" 1199-1213"},"PeriodicalIF":5.4,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964556","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}
Meng Tao, Junying Mao, Guichao Wang, Yu Jiang, Guiwei Li, Kun Zhang, Lanying Sun and Guang Yang
In red raspberry (Rubus idaeus L.), ellagitannins constitute the predominant class of polyphenols, accounting for 53–76% of the total polyphenolic content, and their health-promoting potential is becoming increasingly evident. This review systematically delineates the chemical structures of ellagitannins, extraction and analytical techniques, in vivo metabolic pathways, and their multiple biological activities. It aims to provide the food science and nutrition community with an authoritative reference on ellagitannins in red raspberry and to guide their development and application as core ingredients for next-generation functional foods and nutraceuticals.
{"title":"Ellagitannins from red raspberry (Rubus idaeus L.): a comprehensive review on chemistry characteristics and beneficial effects","authors":"Meng Tao, Junying Mao, Guichao Wang, Yu Jiang, Guiwei Li, Kun Zhang, Lanying Sun and Guang Yang","doi":"10.1039/D5FO04185F","DOIUrl":"10.1039/D5FO04185F","url":null,"abstract":"<p >In red raspberry (<em>Rubus idaeus</em> L.), ellagitannins constitute the predominant class of polyphenols, accounting for 53–76% of the total polyphenolic content, and their health-promoting potential is becoming increasingly evident. This review systematically delineates the chemical structures of ellagitannins, extraction and analytical techniques, <em>in vivo</em> metabolic pathways, and their multiple biological activities. It aims to provide the food science and nutrition community with an authoritative reference on ellagitannins in red raspberry and to guide their development and application as core ingredients for next-generation functional foods and nutraceuticals.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" 3","pages":" 1127-1144"},"PeriodicalIF":5.4,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958276","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}
Angélique Berthomé, Asma El Aoud, Sébastien Marze, Charlotte Sabran, Donato Vairo and Emmanuelle Reboul
We investigated whether low (L) or high (H) amounts of tricaprylin (TC) or triolein (TO) modulate fat-soluble vitamin bioavailability. Mice received 5 mg kg−1 vitamins with either 117 or 933 mg kg−1 of TC or TO. The vitamin levels were monitored in the plasma (0–6 h) and intestine (6 h). The plasma vitamin A response was up to 87.6 ± 3.2% higher (p < 0.0001) with LTC compared to HTC or HTO. The vitamin D response remained unaffected. The plasma vitamin E and K responses were both favored by HTO (up to +283.9 ± 24.0%, p < 0.0001 and +163.8 ± 34.7%, p = 0.033, respectively). The intestinal vitamin A, E and K concentrations reflected the modulations observed in the plasma, while the intestinal vitamin D concentration was significantly higher with HTC compared to LTC (796.9 ± 80.8 vs. 457.1 ± 46.3 pmol g−1, p = 0.0340). Overall, the type and amount of triglycerides influence the bioavailability of vitamins A, E and K but not that of vitamin D. These results could help in formulating fortified foods.
{"title":"Both the type and amount of triglycerides influence the bioavailability of fat-soluble vitamins in mice","authors":"Angélique Berthomé, Asma El Aoud, Sébastien Marze, Charlotte Sabran, Donato Vairo and Emmanuelle Reboul","doi":"10.1039/D5FO03891J","DOIUrl":"10.1039/D5FO03891J","url":null,"abstract":"<p >We investigated whether low (L) or high (H) amounts of tricaprylin (TC) or triolein (TO) modulate fat-soluble vitamin bioavailability. Mice received 5 mg kg<small><sup>−1</sup></small> vitamins with either 117 or 933 mg kg<small><sup>−1</sup></small> of TC or TO. The vitamin levels were monitored in the plasma (0–6 h) and intestine (6 h). The plasma vitamin A response was up to 87.6 ± 3.2% higher (<em>p</em> < 0.0001) with LTC compared to HTC or HTO. The vitamin D response remained unaffected. The plasma vitamin E and K responses were both favored by HTO (up to +283.9 ± 24.0%, <em>p</em> < 0.0001 and +163.8 ± 34.7%, <em>p</em> = 0.033, respectively). The intestinal vitamin A, E and K concentrations reflected the modulations observed in the plasma, while the intestinal vitamin D concentration was significantly higher with HTC compared to LTC (796.9 ± 80.8 <em>vs.</em> 457.1 ± 46.3 pmol g<small><sup>−1</sup></small>, <em>p</em> = 0.0340). Overall, the type and amount of triglycerides influence the bioavailability of vitamins A, E and K but not that of vitamin D. These results could help in formulating fortified foods.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" 3","pages":" 1326-1335"},"PeriodicalIF":5.4,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964583","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}