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Therapeutic potential of Phoenix dactylifera pulp and seed extracts in mitigating oxidative stress and organ dysfunction in testosterone-induced polycystic ovary syndrome
IF 3.8 2区 农林科学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-03-22 DOI: 10.1016/j.jff.2025.106743
Maryam Sana , Muhammad Arshad , Farzana Siddique , Hafiz Muhammad Irfan , Mulazim Hussain Asim , Waseem Khalid , Robert Mugabi , Tawfiq Alsulami , Gulzar Ahmad Nayik
Polycystic ovary syndrome is associated with metabolic disorders, infertility and chronic diseases. Dietary nutrients playing vital role, Ajwa dates (Phoenix Dactylifera) known for exceptional nutritional and therapeutic properties, were tested as an alternative to polypharmacy. The aim was to explore the potential reversibility of oxidative stress and mitigate the kidney and liver damage associated with PCOS. PCOS was induced through testosterone enanthate (1.0 mg/100 g/BW) injection for 35-days. Ajwa whole date and seed extracts (500, 1000, and 2000 mg/kgBW) administered for 28 days, alongside metformin (250 mg/kgBW). Phytochemical profiling was conducted using HPLC and FTIR techniques. The results, revealing the effects of treatments, exposure duration, and their interactions in groups treated with metformin and Ajwa dates. Their treatment showed significant improvements (p < 0 0.001) in hormonal profile, liver and kidney function and oxidative stress markers compared to PCOS group. These finding highlight Ajwa dates potential as natural therapeutic option for managing PCOS and associated complications.
{"title":"Therapeutic potential of Phoenix dactylifera pulp and seed extracts in mitigating oxidative stress and organ dysfunction in testosterone-induced polycystic ovary syndrome","authors":"Maryam Sana ,&nbsp;Muhammad Arshad ,&nbsp;Farzana Siddique ,&nbsp;Hafiz Muhammad Irfan ,&nbsp;Mulazim Hussain Asim ,&nbsp;Waseem Khalid ,&nbsp;Robert Mugabi ,&nbsp;Tawfiq Alsulami ,&nbsp;Gulzar Ahmad Nayik","doi":"10.1016/j.jff.2025.106743","DOIUrl":"10.1016/j.jff.2025.106743","url":null,"abstract":"<div><div>Polycystic ovary syndrome is associated with metabolic disorders, infertility and chronic diseases. Dietary nutrients playing vital role, Ajwa dates (<em>Phoenix Dactylifera</em>) known for exceptional nutritional and therapeutic properties, were tested as an alternative to polypharmacy. The aim was to explore the potential reversibility of oxidative stress and mitigate the kidney and liver damage associated with PCOS. PCOS was induced through testosterone enanthate (1.0 mg/100 g/BW) injection for 35-days. Ajwa whole date and seed extracts (500, 1000, and 2000 mg/kgBW) administered for 28 days, alongside metformin (250 mg/kgBW). Phytochemical profiling was conducted using HPLC and FTIR techniques. The results, revealing the effects of treatments, exposure duration, and their interactions in groups treated with metformin and Ajwa dates. Their treatment showed significant improvements (<em>p</em> &lt; 0 0.001) in hormonal profile, liver and kidney function and oxidative stress markers compared to PCOS group. These finding highlight Ajwa dates potential as natural therapeutic option for managing PCOS and associated complications.</div></div>","PeriodicalId":360,"journal":{"name":"Journal of Functional Foods","volume":"127 ","pages":"Article 106743"},"PeriodicalIF":3.8,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Anti-obesity effect of isoliquiritigenin in the 3T3-L1 cell line and a high-fat diet-induced obesity mice model
IF 3.8 2区 农林科学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-03-21 DOI: 10.1016/j.jff.2025.106735
Le Zhao , Minhao Li , Qingjun Zhu, Haili Yang, Yongju Zhao
Excessive fat can lead to obesity and health risks. Increasing thermogenesis and lipolysis are effective obesity treatments. Isoliquiritigenin (ISL), found in licorice, has antioxidant, anti-inflammatory, antiviral, and anticancer properties. However, its anti-obesity effects are poorly understood. Mice treated with 50 mg/kg/d ISL for 8 weeks showed significantly lower adipose tissue weight and smaller adipocytes, indicating reduced lipid accumulation. ISL increased UCP1, HSL, and ATGL expression and electron transport chain protein levels in adipose tissue, suggesting enhanced thermogenesis and lipolysis. ISL also reduced HFD-induced adipose tissue inflammation. Additionally, ISL inhibited preadipocyte differentiation in 3T3-L1 cells by suppressing ERK/P38-MAPK signaling. These findings highlight ISL's potential as a nutraceutical agent against obesity.
{"title":"Anti-obesity effect of isoliquiritigenin in the 3T3-L1 cell line and a high-fat diet-induced obesity mice model","authors":"Le Zhao ,&nbsp;Minhao Li ,&nbsp;Qingjun Zhu,&nbsp;Haili Yang,&nbsp;Yongju Zhao","doi":"10.1016/j.jff.2025.106735","DOIUrl":"10.1016/j.jff.2025.106735","url":null,"abstract":"<div><div>Excessive fat can lead to obesity and health risks. Increasing thermogenesis and lipolysis are effective obesity treatments. Isoliquiritigenin (ISL), found in licorice, has antioxidant, anti-inflammatory, antiviral, and anticancer properties. However, its anti-obesity effects are poorly understood. Mice treated with 50 mg/kg/d ISL for 8 weeks showed significantly lower adipose tissue weight and smaller adipocytes, indicating reduced lipid accumulation. ISL increased UCP1, HSL, and ATGL expression and electron transport chain protein levels in adipose tissue, suggesting enhanced thermogenesis and lipolysis. ISL also reduced HFD-induced adipose tissue inflammation. Additionally, ISL inhibited preadipocyte differentiation in 3T3-L1 cells by suppressing ERK/P38-MAPK signaling. These findings highlight ISL's potential as a nutraceutical agent against obesity.</div></div>","PeriodicalId":360,"journal":{"name":"Journal of Functional Foods","volume":"127 ","pages":"Article 106735"},"PeriodicalIF":3.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring the structure–activity relationships and molecular mechanisms of food-derived antioxidative peptides in mitigating oxidative stress: A comprehensive review
IF 3.8 2区 农林科学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-03-21 DOI: 10.1016/j.jff.2025.106751
Atif Ali , Kiran Kareem Bukhsh , Muhammad Mohsin Raza , Muhammad Talha Afraz , Tazeddinova Diana , Muhammad Waseem , Muhammad Faisal Manzoor , Gholamreza Abdi
Oxidative stress is mainly attributed to the overproduction of reactive oxygen or nitrogen species during mitochondrial electron transport chain reactions. The presence of these reactive species correlates with metabolic conditions, including inflammation, aging, and neurodegeneration. Food-derived bioactive peptides exhibit antioxidative abilities potentially dependent on processing conditions and structural characteristics, including molecular weight and amino acid sequences. This review summarizes recent advances in generating food protein-derived antioxidant peptides and comprehensively explores comparative structural characterization as the basis for examining the molecular mechanisms underlying anti-oxidative potential in mammalian cells. Enzymatically produced antioxidant peptides with molecular weight ˂3 kDa and short amino acid sequences typically exhibit enhanced intestinal epithelial membrane permeability via enterocytes, tight junctions, and passive diffusion, exerting antioxidative potential. Their antioxidative potential is associated with decreased intracellular reactive oxygen species and malondialdehyde production. Additionally, they enhance the defense capabilities of enzymatic (superoxide dismutase and catalase) and non-enzymatic antioxidants (ascorbic acid and alpha-tocopherol). Mechanistically, they regulate major oxidative protein pathways, including Keap1-Nrf2-ARE, MAPK, NF-κB, and PI3K/AKT/mTOR. Intriguingly, plants and animal-derived peptides exhibit different structural characteristics. Plant-derived peptides tend to be negatively charged, making them more soluble with greater bioavailability. Future researchers should focus on developing new technologies for large-scale commercial production of food protein-derived antioxidant peptides and verifying their health benefits in vivo while addressing limitations and safety considerations.
{"title":"Exploring the structure–activity relationships and molecular mechanisms of food-derived antioxidative peptides in mitigating oxidative stress: A comprehensive review","authors":"Atif Ali ,&nbsp;Kiran Kareem Bukhsh ,&nbsp;Muhammad Mohsin Raza ,&nbsp;Muhammad Talha Afraz ,&nbsp;Tazeddinova Diana ,&nbsp;Muhammad Waseem ,&nbsp;Muhammad Faisal Manzoor ,&nbsp;Gholamreza Abdi","doi":"10.1016/j.jff.2025.106751","DOIUrl":"10.1016/j.jff.2025.106751","url":null,"abstract":"<div><div>Oxidative stress is mainly attributed to the overproduction of reactive oxygen or nitrogen species during mitochondrial electron transport chain reactions. The presence of these reactive species correlates with metabolic conditions, including inflammation, aging, and neurodegeneration. Food-derived bioactive peptides exhibit antioxidative abilities potentially dependent on processing conditions and structural characteristics, including molecular weight and amino acid sequences. This review summarizes recent advances in generating food protein-derived antioxidant peptides and comprehensively explores comparative structural characterization as the basis for examining the molecular mechanisms underlying anti-oxidative potential in mammalian cells. Enzymatically produced antioxidant peptides with molecular weight ˂3 kDa and short amino acid sequences typically exhibit enhanced intestinal epithelial membrane permeability <em>via</em> enterocytes, tight junctions, and passive diffusion, exerting antioxidative potential. Their antioxidative potential is associated with decreased intracellular reactive oxygen species and malondialdehyde production. Additionally, they enhance the defense capabilities of enzymatic (superoxide dismutase and catalase) and non-enzymatic antioxidants (ascorbic acid and alpha-tocopherol). Mechanistically, they regulate major oxidative protein pathways, including Keap1-Nrf2-ARE, MAPK, NF-κB, and PI3K/AKT/mTOR. Intriguingly, plants and animal-derived peptides exhibit different structural characteristics. Plant-derived peptides tend to be negatively charged, making them more soluble with greater bioavailability. Future researchers should focus on developing new technologies for large-scale commercial production of food protein-derived antioxidant peptides and verifying their health benefits <em>in vivo</em> while addressing limitations and safety considerations.</div></div>","PeriodicalId":360,"journal":{"name":"Journal of Functional Foods","volume":"127 ","pages":"Article 106751"},"PeriodicalIF":3.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Gallic acid alleviates Alzheimer's disease by inhibiting p38/MAPK signaling pathway
IF 3.8 2区 农林科学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-03-21 DOI: 10.1016/j.jff.2025.106745
Jiaxin Wang , Qingling Wang , Xinmin Tu , Ruiwen Yang , Jiangning Hu , Jie Kang , Bing Han , Guoyin Kai
Alzheimer's disease (AD) has become a major public health problem worldwide. The effect and mechanism of GA on AD are unclear. We found that GA could inhibit glutamic acid (Glu)-induced neurocyte damage and alleviated disease symptom in D-galactose and AlCl3-induced AD mice. Besides, the doses used for mice can be obtained by human oral administration. GA improved learning and memory abilities while enhanced motor function in AD mice. In addition, GA protected against pathological damage in the hippocampus and cortex tissues of AD mice. The transcriptomic analysis showed that p38/MAPK signaling pathway was involved in GA's protection against AD. Further verification showed that GA significantly inhibited the expression of Gadd45b, Gadd45g, and the phosphorylation of downstream p38 in vitro and in vivo. Together, it suggests that GA can alleviate AD progression by inhibiting p38/MAPK signaling pathway and might be a candidate natural compound for AD prevention.
{"title":"Gallic acid alleviates Alzheimer's disease by inhibiting p38/MAPK signaling pathway","authors":"Jiaxin Wang ,&nbsp;Qingling Wang ,&nbsp;Xinmin Tu ,&nbsp;Ruiwen Yang ,&nbsp;Jiangning Hu ,&nbsp;Jie Kang ,&nbsp;Bing Han ,&nbsp;Guoyin Kai","doi":"10.1016/j.jff.2025.106745","DOIUrl":"10.1016/j.jff.2025.106745","url":null,"abstract":"<div><div>Alzheimer's disease (AD) has become a major public health problem worldwide. The effect and mechanism of GA on AD are unclear. We found that GA could inhibit glutamic acid (Glu)-induced neurocyte damage and alleviated disease symptom in D-galactose and AlCl<sub>3</sub>-induced AD mice. Besides, the doses used for mice can be obtained by human oral administration. GA improved learning and memory abilities while enhanced motor function in AD mice. In addition, GA protected against pathological damage in the hippocampus and cortex tissues of AD mice. The transcriptomic analysis showed that p38/MAPK signaling pathway was involved in GA's protection against AD. Further verification showed that GA significantly inhibited the expression of Gadd45b, Gadd45g, and the phosphorylation of downstream p38 <em>in vitro</em> and <em>in vivo</em>. Together, it suggests that GA can alleviate AD progression by inhibiting p38/MAPK signaling pathway and might be a candidate natural compound for AD prevention.</div></div>","PeriodicalId":360,"journal":{"name":"Journal of Functional Foods","volume":"127 ","pages":"Article 106745"},"PeriodicalIF":3.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting acquired resistance via promoting stemness of EGFR mutant mitigates lung adenocarcinomas progression: Intervention by harpagoside (Xuandanqingjin decoction)
IF 3.8 2区 农林科学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-03-20 DOI: 10.1016/j.jff.2025.106729
Jiamao Lin , Lei Liu , Shengcai Ma , Yuanzhu Jiang , Zhenxiang Li
Non-small-cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide. Resistance to EGFR TKIs and paclitaxel-based chemotherapies in EGFR-mutant lung cancer patients leads to poor prognosis. Effective targeted therapies alone or in combination remain a major clinical challenge. Harpagoside, derived from the Chinese traditional medicine Xuandanqingjin (XDQJ) decoction, has shown potential anti-cancer effects in various tumors. In this study, we used two experimental models to investigate the anti-cancer effect of harpagoside on lung adenocarcinoma progression. We successfully established PC9GR cells resistant to gefitinib. RNA sequencing revealed differential expression of genes related to cancer stem cells and inflammation between PC9 and PC9GR cells. PC9GR formed significantly more and larger colonies compared to PC9 cells. Expression analysis showed reduced E-cadherin and increased Vimentin in PC9GR cells relative to PC9 cells. Tumors in mice treated with both harpagoside and gefitinib had significantly smaller volumes compared to the model and gefitinib-only groups. Additionally, we found that paclitaxel (PTX) in combination with low-concentration harpagoside could sensitize lung cancer cells to PTX treatment, exhibiting synergistic antitumor activity, as indicated by reduced cell proliferation and induced apoptosis. Further findings showed that, in addition to apoptotic cell death, harpagoside combined with PTX significantly triggered ferroptosis in cancer cells, as evidenced by elevated ROS production, lipid peroxidation, and intracellular Fe2+ levels, while decreasing GSH contents. Moreover, harpagoside and PTX combinational treatments markedly reduced cell migration and invasion processes, and such synergistic effects were confirmed in vivo by restrained liver metastasis. Animal analysis also identified suppressive effects of harpagoside and PTX co-treatments on tumor growth in a xenograft mouse model. To gain deeper mechanistic insights into the combinational therapy, RNA-seq assays were conducted. The findings revealed that harpagoside and PTX co-treatments modulated multiple signaling pathways, particularly the Nrf2, apoptosis, and ferroptosis pathways, to exert their anti-tumor potential in cancer cells. Importantly, we found that the synergistic effects of harpagoside and PTX combination on the modulation of proliferation, apoptosis, ferroptosis, and epithelial-to-mesenchymal transition (EMT) events were almost abrogated in cancer cells with Nrf2 overexpression, suggesting that Nrf2 suppression might be required for the combinational therapy-induced cytotoxicity. Collectively, these results suggest that combinational therapy of harpagoside and PTX exhibits promising antitumor activity in lung cancer through depressing Nrf2 signaling.
{"title":"Targeting acquired resistance via promoting stemness of EGFR mutant mitigates lung adenocarcinomas progression: Intervention by harpagoside (Xuandanqingjin decoction)","authors":"Jiamao Lin ,&nbsp;Lei Liu ,&nbsp;Shengcai Ma ,&nbsp;Yuanzhu Jiang ,&nbsp;Zhenxiang Li","doi":"10.1016/j.jff.2025.106729","DOIUrl":"10.1016/j.jff.2025.106729","url":null,"abstract":"<div><div>Non-small-cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide. Resistance to EGFR TKIs and paclitaxel-based chemotherapies in EGFR-mutant lung cancer patients leads to poor prognosis. Effective targeted therapies alone or in combination remain a major clinical challenge. Harpagoside, derived from the Chinese traditional medicine Xuandanqingjin (XDQJ) decoction, has shown potential anti-cancer effects in various tumors. In this study, we used two experimental models to investigate the anti-cancer effect of harpagoside on lung adenocarcinoma progression. We successfully established PC9GR cells resistant to gefitinib. RNA sequencing revealed differential expression of genes related to cancer stem cells and inflammation between PC9 and PC9GR cells. PC9GR formed significantly more and larger colonies compared to PC9 cells. Expression analysis showed reduced E-cadherin and increased Vimentin in PC9GR cells relative to PC9 cells. Tumors in mice treated with both harpagoside and gefitinib had significantly smaller volumes compared to the model and gefitinib-only groups. Additionally, we found that paclitaxel (PTX) in combination with low-concentration harpagoside could sensitize lung cancer cells to PTX treatment, exhibiting synergistic antitumor activity, as indicated by reduced cell proliferation and induced apoptosis. Further findings showed that, in addition to apoptotic cell death, harpagoside combined with PTX significantly triggered ferroptosis in cancer cells, as evidenced by elevated ROS production, lipid peroxidation, and intracellular Fe<sub>2</sub><sup>+</sup> levels, while decreasing GSH contents. Moreover, harpagoside and PTX combinational treatments markedly reduced cell migration and invasion processes, and such synergistic effects were confirmed in vivo by restrained liver metastasis. Animal analysis also identified suppressive effects of harpagoside and PTX co-treatments on tumor growth in a xenograft mouse model. To gain deeper mechanistic insights into the combinational therapy, RNA-seq assays were conducted. The findings revealed that harpagoside and PTX co-treatments modulated multiple signaling pathways, particularly the Nrf2, apoptosis, and ferroptosis pathways, to exert their anti-tumor potential in cancer cells. Importantly, we found that the synergistic effects of harpagoside and PTX combination on the modulation of proliferation, apoptosis, ferroptosis, and epithelial-to-mesenchymal transition (EMT) events were almost abrogated in cancer cells with Nrf2 overexpression, suggesting that Nrf2 suppression might be required for the combinational therapy-induced cytotoxicity. Collectively, these results suggest that combinational therapy of harpagoside and PTX exhibits promising antitumor activity in lung cancer through depressing Nrf2 signaling.</div></div>","PeriodicalId":360,"journal":{"name":"Journal of Functional Foods","volume":"127 ","pages":"Article 106729"},"PeriodicalIF":3.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Caulerpa okamurae extract alleviates pulmonary fibrosis in vitro and in vivo by modulating Tgfβ/SMAD/MAPK signaling and NLRP3 inflammasome activation
IF 3.8 2区 农林科学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-03-19 DOI: 10.1016/j.jff.2025.106734
Seok Hee Seo , Thi My Tien Truong , Hyejin Hyeon , Young-Min Ham , Yong-Hwan Jung , Hyun-Jin Kim , Dong-Shin Kim , Inhae Kang
Pulmonary fibrosis (PF) characterized by fibroblast dysfunction and inflammation, in driven by transforming growth factor beta (Tgfβ) plays a crucial role. Caulerpa okamurae extract (COE), drived from a green seaweed widely consumed in East Asia, is known for its anti-obesity properties, but its effects on PF remain unexplored. This study investigated the potential of the COE in PF using Tgfβ-stimulated MRC-5 lung fibroblasts and bleomycin (BLM)-induced PF in C57BL/6 mice. In vitro, COE significantly reduced fibrotic markers (α-Sma, Mmp1, Col1a1, and Vimentin) and suppressed inflammatory mediators (Il-1β, Il-6, and Cox2) by downregulating Tgfβ/SMAD2/3 and MAPK signaling. In vivo, COE attenuated fibrotic features in BLM-treated mice by modulating the Tgfβ/SMAD/MAPK pathway. Interestingly, COE decreased plasma levels of IL-1β, an indicative of suppressed NLRP3 inflammasome activation. This effect was further validated in lipopolysaccharide and nigericin-treated bone marrow-derived macrophages, where COE inhibited NLRP3 inflammasome activation. These finding highlight COE's action in mitigating fibrosis and inflammation by modulation of Tgfβ/SMAD2/3 and MAPK signaling, along with the NLRP3 inflammasome pathway, underscoring its potential as a novel therapeutic for PF.
肺纤维化(PF)以成纤维细胞功能障碍和炎症为特征,其中转化生长因子β(Tgfβ)起着至关重要的作用。褐藻提取物(Caulerpa okamurae extract,COE)是从一种在东亚广泛食用的绿藻中提取出来的,以其抗肥胖特性而闻名,但其对肺纤维化的影响仍有待探索。本研究利用Tgfβ刺激的MRC-5肺成纤维细胞和博来霉素(BLM)诱导的C57BL/6小鼠PF,研究了COE对PF的潜在作用。在体外,COE通过下调Tgfβ/SMAD2/3和MAPK信号转导,明显减少了纤维化标志物(α-Sma、Mmp1、Col1a1和Vimentin),并抑制了炎症介质(Il-1β、Il-6和Cox2)。在体内,COE 通过调节 Tgfβ/SMAD/MAPK 通路,减轻了 BLM 处理的小鼠的纤维化特征。有趣的是,COE降低了血浆中IL-1β的水平,这表明NLRP3炎性体的激活受到了抑制。这一效应在脂多糖和尼格瑞辛处理的骨髓巨噬细胞中得到了进一步验证,COE抑制了NLRP3炎性体的活化。这些发现凸显了COE通过调节Tgfβ/SMAD2/3和MAPK信号以及NLRP3炎性体通路来减轻纤维化和炎症的作用,强调了它作为一种新型PF疗法的潜力。
{"title":"Caulerpa okamurae extract alleviates pulmonary fibrosis in vitro and in vivo by modulating Tgfβ/SMAD/MAPK signaling and NLRP3 inflammasome activation","authors":"Seok Hee Seo ,&nbsp;Thi My Tien Truong ,&nbsp;Hyejin Hyeon ,&nbsp;Young-Min Ham ,&nbsp;Yong-Hwan Jung ,&nbsp;Hyun-Jin Kim ,&nbsp;Dong-Shin Kim ,&nbsp;Inhae Kang","doi":"10.1016/j.jff.2025.106734","DOIUrl":"10.1016/j.jff.2025.106734","url":null,"abstract":"<div><div>Pulmonary fibrosis (PF) characterized by fibroblast dysfunction and inflammation, in driven by transforming growth factor beta (Tgf<em>β</em>) plays a crucial role. <em>Caulerpa okamurae</em> extract (COE), drived from a green seaweed widely consumed in East Asia, is known for its anti-obesity properties, but its effects on PF remain unexplored. This study investigated the potential of the COE in PF using Tgf<em>β</em>-stimulated MRC-5 lung fibroblasts and bleomycin (BLM)-induced PF in C57BL/6 mice. <em>In vitro</em>, COE significantly reduced fibrotic markers (<em>α-Sma</em>, <em>Mmp1</em>, <em>Col1a1</em>, and <em>Vimentin</em>) and suppressed inflammatory mediators (<em>Il-1β</em>, <em>Il-6</em>, and <em>Cox2</em>) by downregulating Tgfβ/SMAD2/3 and MAPK signaling. <em>In vivo</em>, COE attenuated fibrotic features in BLM-treated mice by modulating the Tgf<em>β</em>/SMAD/MAPK pathway. Interestingly, COE decreased plasma levels of IL-1<em>β</em>, an indicative of suppressed NLRP3 inflammasome activation. This effect was further validated in lipopolysaccharide and nigericin-treated bone marrow-derived macrophages, where COE inhibited NLRP3 inflammasome activation. These finding highlight COE's action in mitigating fibrosis and inflammation by modulation of Tgf<em>β</em>/SMAD2/3 and MAPK signaling, along with the NLRP3 inflammasome pathway, underscoring its potential as a novel therapeutic for PF.</div></div>","PeriodicalId":360,"journal":{"name":"Journal of Functional Foods","volume":"127 ","pages":"Article 106734"},"PeriodicalIF":3.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sulfated glycosaminoglycan from swim bladder mitigates lipid accumulation in Caenorhabditis elegans by mediating the transcription factor NHR-49
IF 3.8 2区 农林科学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-03-19 DOI: 10.1016/j.jff.2025.106724
Yehua Huang , Bingbing Song , Zhuo Wang , Kit Leong Cheong , Rui Li , Qiaoli Zhao , Jing Chen , Saiyi Zhong
Sulfated glycosaminoglycan from swim bladder (SBG) is a marine-derived bioactive polysaccharide structurally similar to chondroitin sulfate A. This study investigates the potential of SBG in mitigating hyperlipidemia linked to lipid metabolism disorders. The results indicate that SBG significantly mitigates glucose-induced metabolic disturbances in C. elegans, including reduced fertility, shortened lifespan, elevated ROS levels, lipofuscin accumulation, and impaired antioxidant responses. Notably, at 1 mg/mL, SBG reduced triglyceride and free fatty acid levels by 56.76 % and 26.64 %, respectively (P < 0.05), as confirmed by Oil Red O staining. At the molecular level, SBG downregulated the expression of lipid metabolism genes, such as daf-2, mdt-15, sbp-1, and acs-2. Additionally, SBG upregulated the expression of nhr-49 and daf-16, which enhanced Δ9-desaturase activity and promoted the synthesis of monounsaturated fatty acids. The deletion of nhr-49 further confirmed that SBG regulates Δ9-desaturase through NHR-49 activation, thereby improving lipid accumulation and preserving metabolic homeostasis.
{"title":"Sulfated glycosaminoglycan from swim bladder mitigates lipid accumulation in Caenorhabditis elegans by mediating the transcription factor NHR-49","authors":"Yehua Huang ,&nbsp;Bingbing Song ,&nbsp;Zhuo Wang ,&nbsp;Kit Leong Cheong ,&nbsp;Rui Li ,&nbsp;Qiaoli Zhao ,&nbsp;Jing Chen ,&nbsp;Saiyi Zhong","doi":"10.1016/j.jff.2025.106724","DOIUrl":"10.1016/j.jff.2025.106724","url":null,"abstract":"<div><div>Sulfated glycosaminoglycan from swim bladder (SBG) is a marine-derived bioactive polysaccharide structurally similar to chondroitin sulfate A. This study investigates the potential of SBG in mitigating hyperlipidemia linked to lipid metabolism disorders. The results indicate that SBG significantly mitigates glucose-induced metabolic disturbances in <em>C. elegans</em>, including reduced fertility, shortened lifespan, elevated ROS levels, lipofuscin accumulation, and impaired antioxidant responses. Notably, at 1 mg/mL, SBG reduced triglyceride and free fatty acid levels by 56.76 % and 26.64 %, respectively (<em>P</em> &lt; 0.05), as confirmed by Oil Red O staining. At the molecular level, SBG downregulated the expression of lipid metabolism genes, such as <em>daf-2</em>, <em>mdt-15</em>, <em>sbp-1</em>, and <em>acs-2</em>. Additionally, SBG upregulated the expression of <em>nhr-49</em> and <em>daf-16</em>, which enhanced Δ9-desaturase activity and promoted the synthesis of monounsaturated fatty acids. The deletion of <em>nhr-49</em> further confirmed that SBG regulates Δ9-desaturase through NHR-49 activation, thereby improving lipid accumulation and preserving metabolic homeostasis.</div></div>","PeriodicalId":360,"journal":{"name":"Journal of Functional Foods","volume":"127 ","pages":"Article 106724"},"PeriodicalIF":3.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Neoagarooligosaccharides improve non-alcoholic fatty liver disease by modulating lipid metabolism and Nrf2-related pathways
IF 3.8 2区 农林科学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-03-19 DOI: 10.1016/j.jff.2025.106737
Subin Bae , Je Hyeon Lee , Su Jung Kim , Ji Hae Yun , Jeongjin Park , Woojin Jun
Neoagarooligosaccharides (NAO), polysaccharides derived from seaweed, exhibit anti-obesity, hepatoprotective, and anti-inflammatory properties. However, their effects on non-alcoholic fatty liver disease (NAFLD) remain underexplored. This study investigates the impact of NAO on lipid accumulation and oxidative stress in free fatty acid (FFA)-treated HepG2 cells and high-fat diet-fed mice. NAO treatment significantly reduced triglyceride and total cholesterol levels, inhibited lipid accumulation (assessed via Oil Red O staining), and lowered liver enzyme levels. NAO also suppressed oxidative stress by enhancing antioxidant enzyme activity and reducing malondialdehyde levels. Real-time PCR and Western blot analyses revealed that NAO modulated lipid transporters, increased AMPK and β-oxidation, and reduced de novo lipogenesis. It also regulated the PI3K/AKT/Nrf2 pathway, suggesting its role in antioxidant defense. These findings highlight NAO's potential as a promising natural compound for developing effective and less toxic therapeutic interventions for NAFLD by mitigating lipid accumulation and oxidative stress.
{"title":"Neoagarooligosaccharides improve non-alcoholic fatty liver disease by modulating lipid metabolism and Nrf2-related pathways","authors":"Subin Bae ,&nbsp;Je Hyeon Lee ,&nbsp;Su Jung Kim ,&nbsp;Ji Hae Yun ,&nbsp;Jeongjin Park ,&nbsp;Woojin Jun","doi":"10.1016/j.jff.2025.106737","DOIUrl":"10.1016/j.jff.2025.106737","url":null,"abstract":"<div><div>Neoagarooligosaccharides (NAO), polysaccharides derived from seaweed, exhibit anti-obesity, hepatoprotective, and anti-inflammatory properties. However, their effects on non-alcoholic fatty liver disease (NAFLD) remain underexplored. This study investigates the impact of NAO on lipid accumulation and oxidative stress in free fatty acid (FFA)-treated HepG2 cells and high-fat diet-fed mice. NAO treatment significantly reduced triglyceride and total cholesterol levels, inhibited lipid accumulation (assessed via Oil Red O staining), and lowered liver enzyme levels. NAO also suppressed oxidative stress by enhancing antioxidant enzyme activity and reducing malondialdehyde levels. Real-time PCR and Western blot analyses revealed that NAO modulated lipid transporters, increased AMPK and β-oxidation, and reduced de novo lipogenesis. It also regulated the PI3K/AKT/Nrf2 pathway, suggesting its role in antioxidant defense. These findings highlight NAO's potential as a promising natural compound for developing effective and less toxic therapeutic interventions for NAFLD by mitigating lipid accumulation and oxidative stress.</div></div>","PeriodicalId":360,"journal":{"name":"Journal of Functional Foods","volume":"127 ","pages":"Article 106737"},"PeriodicalIF":3.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Regulatory effects of Dieckol on inflammatory cytokines and Osteoclastogenesis in Ovariectomized mouse model
IF 3.8 2区 农林科学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-03-18 DOI: 10.1016/j.jff.2025.106731
Eun Hyun Park , Hyung Jin Lim , Nisansala Chandimali , Seon-Gyeong Bak , Eun-Kyung Kim , Sang-Ik Park , Seung-Jae Lee
Dieckol, a major bioactive compound of Ecklonia cava, exhibits antiosteoporosis, anti-inflammatory, antioxidant, and muscle atrophy attenuation properties. This study investigated its effects on IL-6 signaling suppression, estrogen activity, and osteoclastogenesis inhibition. Dieckol inhibited IL-6-induced p-STAT3 activity and downstream signaling molecules like STAT3 and ERK, suppressing the expression of genes such as CRP, IL-1β, SOCS3, and ICAM-1. It attenuated M-CSF/RANKL-induced osteoclastogenesis in mouse bone marrow macrophages and prevented bone loss in an ovariectomized mouse model by improving bone mineral density and microarchitecture. Dieckol also enhanced estrogen receptor activity, upregulating ESR2 while downregulating ESR1, and increased serotonin and norepinephrine levels, potentially alleviating mood disturbances. The doses used were within the safe range in animal studies, and available data indicate good tolerability in humans. These findings suggest dieckol as a promising therapeutic agent for IL-6-mediated or estrogen deficiency-related osteoporosis and associated mood disorders.
{"title":"Regulatory effects of Dieckol on inflammatory cytokines and Osteoclastogenesis in Ovariectomized mouse model","authors":"Eun Hyun Park ,&nbsp;Hyung Jin Lim ,&nbsp;Nisansala Chandimali ,&nbsp;Seon-Gyeong Bak ,&nbsp;Eun-Kyung Kim ,&nbsp;Sang-Ik Park ,&nbsp;Seung-Jae Lee","doi":"10.1016/j.jff.2025.106731","DOIUrl":"10.1016/j.jff.2025.106731","url":null,"abstract":"<div><div>Dieckol, a major bioactive compound of Ecklonia cava, exhibits antiosteoporosis, anti-inflammatory, antioxidant, and muscle atrophy attenuation properties. This study investigated its effects on IL-6 signaling suppression, estrogen activity, and osteoclastogenesis inhibition. Dieckol inhibited IL-6-induced p-STAT3 activity and downstream signaling molecules like STAT3 and ERK, suppressing the expression of genes such as CRP, IL-1β, SOCS3, and ICAM-1. It attenuated M-CSF/RANKL-induced osteoclastogenesis in mouse bone marrow macrophages and prevented bone loss in an ovariectomized mouse model by improving bone mineral density and microarchitecture. Dieckol also enhanced estrogen receptor activity, upregulating ESR2 while downregulating ESR1, and increased serotonin and norepinephrine levels, potentially alleviating mood disturbances. The doses used were within the safe range in animal studies, and available data indicate good tolerability in humans. These findings suggest dieckol as a promising therapeutic agent for IL-6-mediated or estrogen deficiency-related osteoporosis and associated mood disorders.</div></div>","PeriodicalId":360,"journal":{"name":"Journal of Functional Foods","volume":"127 ","pages":"Article 106731"},"PeriodicalIF":3.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Polysaccharide fraction isolated from Korean Saccharina japonica alleviates impaired immune responses in macrophages and immunosuppressed mice
IF 3.8 2区 农林科学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-03-18 DOI: 10.1016/j.jff.2025.106733
Seung-U Son , Min Seung Park , Bong-Keun Jang , Hye-Yeon Kang , Kwang-Soon Shin
This research aimed to investigate the immunostimulating properties of polysaccharides extracted from Saccharina japonica (SJP). Initially, the SJP was a heteropolysaccharide composed of seven different monosaccharides, such as fucose, galactose, mannose, glucuronic acid, guluronic acid, and mannuronic acid. The SJP stimulated the release of NO, IL-6, and TNF-α and mRNA expression of macrophage. Furthermore, these outcomes were closely associated with immunostimulatory signaling pathways including MAPK and NF-κB. Additionally, immunostimulation by SJP is caused by various pattern recognition receptors including dectin-1, SR, and CD14. Prophylactic administration of SJP effectively prevented the toxicity of cyclophosphamide on body weight and the spleen index. In addition, SJP improved the function of various splenic immunocytes such as natural killer cells, CD4+, CD8+, CD11b+, and CD45R+ cells. Especially, the improvement effects on serum IL-6, TNF-α, IgA, and IgG were notable. These results suggest that polysaccharides isolated from S. japonica have high potential as immunomodulators.
{"title":"Polysaccharide fraction isolated from Korean Saccharina japonica alleviates impaired immune responses in macrophages and immunosuppressed mice","authors":"Seung-U Son ,&nbsp;Min Seung Park ,&nbsp;Bong-Keun Jang ,&nbsp;Hye-Yeon Kang ,&nbsp;Kwang-Soon Shin","doi":"10.1016/j.jff.2025.106733","DOIUrl":"10.1016/j.jff.2025.106733","url":null,"abstract":"<div><div>This research aimed to investigate the immunostimulating properties of polysaccharides extracted from <em>Saccharina japonica</em> (SJP). Initially, the SJP was a heteropolysaccharide composed of seven different monosaccharides, such as fucose, galactose, mannose, glucuronic acid, guluronic acid, and mannuronic acid. The SJP stimulated the release of NO, IL-6, and TNF-α and mRNA expression of macrophage. Furthermore, these outcomes were closely associated with immunostimulatory signaling pathways including MAPK and NF-κB. Additionally, immunostimulation by SJP is caused by various pattern recognition receptors including dectin-1, SR, and CD14. Prophylactic administration of SJP effectively prevented the toxicity of cyclophosphamide on body weight and the spleen index. In addition, SJP improved the function of various splenic immunocytes such as natural killer cells, CD4<sup>+</sup>, CD8<sup>+</sup>, CD11b<sup>+</sup>, and CD45R<sup>+</sup> cells. Especially, the improvement effects on serum IL-6, TNF-α, IgA, and IgG were notable. These results suggest that polysaccharides isolated from <em>S. japonica</em> have high potential as immunomodulators.</div></div>","PeriodicalId":360,"journal":{"name":"Journal of Functional Foods","volume":"127 ","pages":"Article 106733"},"PeriodicalIF":3.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Journal of Functional Foods
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