Pub Date : 2025-03-19DOI: 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.
{"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 , Thi My Tien Truong , Hyejin Hyeon , Young-Min Ham , Yong-Hwan Jung , Hyun-Jin Kim , Dong-Shin Kim , 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}
Pub Date : 2025-03-19DOI: 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 , Bingbing Song , Zhuo Wang , Kit Leong Cheong , Rui Li , Qiaoli Zhao , Jing Chen , 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> < 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}
Pub Date : 2025-03-19DOI: 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 , Je Hyeon Lee , Su Jung Kim , Ji Hae Yun , Jeongjin Park , 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}
Pub Date : 2025-03-18DOI: 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 , Hyung Jin Lim , Nisansala Chandimali , Seon-Gyeong Bak , Eun-Kyung Kim , Sang-Ik Park , 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}
Pub Date : 2025-03-18DOI: 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 , Min Seung Park , Bong-Keun Jang , Hye-Yeon Kang , 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}
Pub Date : 2025-03-18DOI: 10.1016/j.jff.2025.106727
Xi Wang , Shuangzhi Chen , Chengyang Li , Le Cheng , Chenhui Lv , Lushan Xue , Cheng Zhang , Xuemin Li , Ruolin Yan , Mingkai Li , Qinfei Guo , Haifeng Zhao
Macrophages are the key cells of liver inflammation-immune regulation in a dynamic polarized state, which can differentiate into pro-inflammatory M1-like and anti-inflammatory M2-like in response to different micro-environmental signals. Insulin resistance (IR) and inflammation induced by the increased M1-like macrophages and decreased M2-like macrophages is a key component in the progression of aged type 2 diabetes mellitus (T2DM) combined with nonalcoholic fatty liver disease (NAFLD) and have become a new target for regulating glycolipid metabolism in recent years. In this study, we found that tea polyphenols (TP) can improve aged T2DM combined with NAFLD by modulating macrophage polarization in liver. More specifically, we have further demonstrated that TP promotes M2-like macrophages by activating the JAK2/STAT3 signaling pathway, and then protects the liver injury exacerbated by IR and inflammation. The results of this study can provide new ideas for the prevention and treatment of aged T2DM combined with NAFLD.
{"title":"Tea polyphenols ameliorates insulin resistance and inflammation by modulating macrophage polarization via JAK2/STAT3 pathway in aged T2DM combined with NAFLD rats","authors":"Xi Wang , Shuangzhi Chen , Chengyang Li , Le Cheng , Chenhui Lv , Lushan Xue , Cheng Zhang , Xuemin Li , Ruolin Yan , Mingkai Li , Qinfei Guo , Haifeng Zhao","doi":"10.1016/j.jff.2025.106727","DOIUrl":"10.1016/j.jff.2025.106727","url":null,"abstract":"<div><div>Macrophages are the key cells of liver inflammation-immune regulation in a dynamic polarized state, which can differentiate into pro-inflammatory M1-like and anti-inflammatory M2-like in response to different micro-environmental signals. Insulin resistance (IR) and inflammation induced by the increased M1-like macrophages and decreased M2-like macrophages is a key component in the progression of aged type 2 diabetes mellitus (T2DM) combined with nonalcoholic fatty liver disease (NAFLD) and have become a new target for regulating glycolipid metabolism in recent years. In this study, we found that tea polyphenols (TP) can improve aged T2DM combined with NAFLD by modulating macrophage polarization in liver. More specifically, we have further demonstrated that TP promotes M2-like macrophages by activating the JAK2/STAT3 signaling pathway, and then protects the liver injury exacerbated by IR and inflammation. The results of this study can provide new ideas for the prevention and treatment of aged T2DM combined with NAFLD.</div></div>","PeriodicalId":360,"journal":{"name":"Journal of Functional Foods","volume":"127 ","pages":"Article 106727"},"PeriodicalIF":3.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643248","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}
Pub Date : 2025-03-17DOI: 10.1016/j.jff.2025.106719
Miaoyunhuan Wang , Xiyue Wang , Xiaobin Li , Yuqing Dong , Jiahao Yu , Peihai Li , Rongchun Wang , Qing Xia , Kechun Liu , Houwen Lin
Chenopodium album L., is a folk potherb as well as a traditional herbal medicine, which valued for its rich material ingredients and pharmacological effects. However, its pharmacological substance basis and potential molecular mechanisms of the anti-inflammatory effect have still not been fully elucidated. The present study aims to investigate its active fractions, material basis and action mechanism of C. album to cure inflammation. First of all, C. album was extracted by 95 % ethanol, and was separated to four fractions via macroporous resin. Then we confirmed the typically anti-inflammatory active fraction CA-A with the best anti-inflammatory effect by CuSO4-induced inflammatory zebrafish model. Subsequently, the main components of CA-A were identified as amino acids and their derivatives and saccharides by UPLC-Q-TOF-MS. And the comprehensive evaluation of anti-inflammatory effect for CA-A indicated that CA-A inhibited inflammatory cells migration in zebrafish with a dose-dependent manner, and promote the up-regulation of IL-10 and the down-regulation of TNF-α and IL-1β. Eventually, network pharmacology and transcriptomic analysis, together with RT-qPCR verification revealed that CA-A suppressed inflammation progression by down-regulating PI3K/AKT, MAPK, and NF-κB signaling pathways and up-regulating PPAR signaling pathway. These findings offered guidance for its potential applications of C. album and provide a novel foundation for development of CA-A as functional food to inhibit inflammation.
{"title":"Chenopodium album L. herb attenuates inflammation by modulating multiple signaling pathways in zebrafish: Network pharmacology analysis, transcriptomics analysis and experimental verification","authors":"Miaoyunhuan Wang , Xiyue Wang , Xiaobin Li , Yuqing Dong , Jiahao Yu , Peihai Li , Rongchun Wang , Qing Xia , Kechun Liu , Houwen Lin","doi":"10.1016/j.jff.2025.106719","DOIUrl":"10.1016/j.jff.2025.106719","url":null,"abstract":"<div><div><em>Chenopodium album</em> L., is a folk potherb as well as a traditional herbal medicine, which valued for its rich material ingredients and pharmacological effects. However, its pharmacological substance basis and potential molecular mechanisms of the anti-inflammatory effect have still not been fully elucidated. The present study aims to investigate its active fractions, material basis and action mechanism of <em>C. album</em> to cure inflammation. First of all, <em>C. album</em> was extracted by 95 % ethanol, and was separated to four fractions via macroporous resin. Then we confirmed the typically anti-inflammatory active fraction CA-A with the best anti-inflammatory effect by CuSO<sub>4</sub>-induced inflammatory zebrafish model. Subsequently, the main components of CA-A were identified as amino acids and their derivatives and saccharides by UPLC-Q-TOF-MS. And the comprehensive evaluation of anti-inflammatory effect for CA-A indicated that CA-A inhibited inflammatory cells migration in zebrafish with a dose-dependent manner, and promote the up-regulation of IL-10 and the down-regulation of TNF-α and IL-1β. Eventually, network pharmacology and transcriptomic analysis, together with RT-qPCR verification revealed that CA-A suppressed inflammation progression by down-regulating PI3K/AKT, MAPK, and NF-κB signaling pathways and up-regulating PPAR signaling pathway. These findings offered guidance for its potential applications of <em>C. album</em> and provide a novel foundation for development of CA-A as functional food to inhibit inflammation.</div></div>","PeriodicalId":360,"journal":{"name":"Journal of Functional Foods","volume":"127 ","pages":"Article 106719"},"PeriodicalIF":3.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143637225","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}
Pub Date : 2025-03-16DOI: 10.1016/j.jff.2025.106715
Jie Luo , Dai Lu , Ruiyi Zhang , Bin Long , Liang Chen , Wei Wang , Xing Tian
Low-calorie sweeteners, also known as non-nutritive sweeteners (NNSs), have been widely used in the food industry for decades to replace sugar due to their ability to reduce calories in foods and beverages while maintaining sweetness. Nonetheless, numerous controversies persist regarding the long-term effects of various types of NNSs on human physiology and their metabolic safety. Therefore, the aim of this study was to evaluate the effects of long-term consumption of various types of sweet water on metabolism, gut microbiota and their potential mechanisms of action in male SD rats (n = 24). Purified water (WAT), 5 % sucrose solution (SUC) (5 mg/mL), and sucralose solution (TGS) (0.0833 mg/mL) and mogroside solution (MOG) (0.2 mg/mL) with the same sweetness as 5 % sucrose were continuously administered for a period of 15 weeks and then the fat content, blood glucose levels, and blood lipids of male SD rats were measured. Additionally, the interaction between intestinal metabolic disorders and intestinal microbiota abnormalities was analyzed using targeted metabolomics combined with 16S rRNA gene sequencing. The findings suggest that NNSs, while not having a significant effect on body weight, may lead to obesity and metabolic disorders in the long-term consumption of sweet water. Mogroside has preferably physiological characteristics, including reducing obesity and improving metabolic disorders, additionally the capacity to enrich beneficial bacteria (Akkermansia and Allobaculum). Conversely, sucralose is similar to sucrose, both of them were observed to promote the growth of harmful bacteria (Corynebacterium and Alloprevotella), exacerbate obesity and metabolic impairment. Moreover, long-term consumption of sweet water affected the transduction mechanism of sweet taste, which in turn synergy with other metabolic pathways, affected the glycolipid metabolism and altered the composition of the gut microbiota. This research provides a theoretical basis for the rational development and use of non-nutritive sweeteners.
{"title":"What exactly happens to rats that drink different types of sweetness water over a long time:A comparison with sucrose, artificial sweeteners and natural sweeteners","authors":"Jie Luo , Dai Lu , Ruiyi Zhang , Bin Long , Liang Chen , Wei Wang , Xing Tian","doi":"10.1016/j.jff.2025.106715","DOIUrl":"10.1016/j.jff.2025.106715","url":null,"abstract":"<div><div>Low-calorie sweeteners, also known as non-nutritive sweeteners (NNSs), have been widely used in the food industry for decades to replace sugar due to their ability to reduce calories in foods and beverages while maintaining sweetness. Nonetheless, numerous controversies persist regarding the long-term effects of various types of NNSs on human physiology and their metabolic safety. Therefore, the aim of this study was to evaluate the effects of long-term consumption of various types of sweet water on metabolism, gut microbiota and their potential mechanisms of action in male SD rats (<em>n</em> = 24). Purified water (WAT), 5 % sucrose solution (SUC) (5 mg/mL), and sucralose solution (TGS) (0.0833 mg/mL) and mogroside solution (MOG) (0.2 mg/mL) with the same sweetness as 5 % sucrose were continuously administered for a period of 15 weeks and then the fat content, blood glucose levels, and blood lipids of male SD rats were measured. Additionally, the interaction between intestinal metabolic disorders and intestinal microbiota abnormalities was analyzed using targeted metabolomics combined with 16S rRNA gene sequencing. The findings suggest that NNSs, while not having a significant effect on body weight, may lead to obesity and metabolic disorders in the long-term consumption of sweet water. Mogroside has preferably physiological characteristics, including reducing obesity and improving metabolic disorders, additionally the capacity to enrich beneficial bacteria (<em>Akkermansia</em> and <em>Allobaculum</em>). Conversely, sucralose is similar to sucrose, both of them were observed to promote the growth of harmful bacteria (<em>Corynebacterium</em> and <em>Alloprevotella</em>), exacerbate obesity and metabolic impairment. Moreover, long-term consumption of sweet water affected the transduction mechanism of sweet taste, which in turn synergy with other metabolic pathways, affected the glycolipid metabolism and altered the composition of the gut microbiota. This research provides a theoretical basis for the rational development and use of non-nutritive sweeteners.</div></div>","PeriodicalId":360,"journal":{"name":"Journal of Functional Foods","volume":"127 ","pages":"Article 106715"},"PeriodicalIF":3.8,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143632008","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}
Pub Date : 2025-03-15DOI: 10.1016/j.jff.2025.106720
Lin Liang , Yu Wang , Haoran Chen , Jianrong Huo , Shilong Yu , Junxing Zhao
Sea buckthorn (SB) berries, which are non-toxic, contain diverse bioactive substances with high nutritional value and beneficial medicinal properties. This study aims to explore the effects of maternal dietary SB during pregnancy and lactation on high-fat diet (HFD) induced obesity in offspring. The results showed that maternal SB intake reduced offspring body weight and fat mass, and improved both glucose tolerance and insulin sensitivity. Furthermore, offspring of dams fed SB exhibited lower expression of inflammatory response factors, such as IL-6, IL-10, and TNF-α, and higher energy metabolism in BAT to resist the cold environment than the descendants of only HFD-fed dams. Meanwhile, markers for BAT were dramatically upregulated in offspring of HFDSB-fed dams. Finally, dietary SB restored the number of functional mitochondria by increasing PKM2 and FASN expression. Taken together, this study reveals a novel approach for alleviating offspring obesity induced by HFD in terms of maternal SB supplementation.
{"title":"Dietary Sea buckthorn during pregnancy reverses offspring obesity by alleviating BAT dysfunction","authors":"Lin Liang , Yu Wang , Haoran Chen , Jianrong Huo , Shilong Yu , Junxing Zhao","doi":"10.1016/j.jff.2025.106720","DOIUrl":"10.1016/j.jff.2025.106720","url":null,"abstract":"<div><div>Sea buckthorn (SB) berries, which are non-toxic, contain diverse bioactive substances with high nutritional value and beneficial medicinal properties. This study aims to explore the effects of maternal dietary SB during pregnancy and lactation on high-fat diet (HFD) induced obesity in offspring. The results showed that maternal SB intake reduced offspring body weight and fat mass, and improved both glucose tolerance and insulin sensitivity. Furthermore, offspring of dams fed SB exhibited lower expression of inflammatory response factors, such as IL-6, IL-10, and TNF-α, and higher energy metabolism in BAT to resist the cold environment than the descendants of only HFD-fed dams. Meanwhile, markers for BAT were dramatically upregulated in offspring of HFDSB-fed dams. Finally, dietary SB restored the number of functional mitochondria by increasing PKM2 and FASN expression. Taken together, this study reveals a novel approach for alleviating offspring obesity induced by HFD in terms of maternal SB supplementation.</div></div>","PeriodicalId":360,"journal":{"name":"Journal of Functional Foods","volume":"127 ","pages":"Article 106720"},"PeriodicalIF":3.8,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628576","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}
Pub Date : 2025-03-15DOI: 10.1016/j.jff.2025.106730
Asad Ur Rahman , Naveed Ullah Khan , Pharkphoom Panichayupakaranant , Jiang Ni
Chamuangone is a polyprenylated benzophenone found in the leaves of the Thai vegetable Garcinia cowa Roxb., which has been reported for its in vitro anticancer properties. The leaves have traditionally been used for the treatment of inflammation, infections, and diabetes. In this study, a standardized chamuangone-enriched extract (CEE) from G. cowa leaves, containing 73.0 ± 2.0 % w/w of chamuangone, was evaluated in vitro and in vivo in allograft models (4 T1-luc cells) of breast cancer (BC) and metastatic breast cancer (MBC). The effects of CEE on 4 T1-luc cell viability, apoptosis, cell cycle, and cell migration were analyzed using CCK-8, flow cytometry, and wound healing assays. The in vivo antitumor and antimetastatic efficacy of CEE at doses of 25, 50, and 100 mg/kg body weight (b.w.) was evaluated in BALB/c mice. Tumor markers (CEA, CA 125, CA 15–3), apoptotic markers (p53, Bcl-2), and inflammatory markers (MMP-2, MMP-9, IL-6, NF-κB, and TNF-α) were assessed using ELISA assays. Additionally, the pharmacokinetic and biodistribution profiles of CEE were assessed using the normal mice. The results revealed that CEE (10 µg/mL) decreased 4 T1-luc cell viability, with IC50 values of 62.5, 48.07, and 31.18 μg/mL at 24, 48, and 72 h, respectively. CEE induced early apoptosis (18.38 %) and late apoptosis (42.79 %), inhibited cell migration and triggered cell cycle arrest, with 59.92 % of cells in the subG1 phase. Furthermore, CEE at 100 mg/kg b.w., significantly inhibited tumor growth and metastasis, in vivo and significantly modulating apoptotic, tumor, and inflammatory markers. The plasma half-life (t½) of CEE at 100 mg/kg b.w. was found to be 11 h. The liver achieved the maximum concentration of chamuangone, followed by the spleen, kidneys, lungs, and heart. Based on the preclinical safety assessment of CEE, a green extract, a dose of 100 mg/kg b.w. is considered safe for therapeutic application as a chemopreventive functional ingredient in BC treatment.
{"title":"A standardized chamuangone enriched extract shows anticancer efficacy in allograft models of metastatic breast cancer","authors":"Asad Ur Rahman , Naveed Ullah Khan , Pharkphoom Panichayupakaranant , Jiang Ni","doi":"10.1016/j.jff.2025.106730","DOIUrl":"10.1016/j.jff.2025.106730","url":null,"abstract":"<div><div>Chamuangone is a polyprenylated benzophenone found in the leaves of the Thai vegetable <em>Garcinia cowa</em> Roxb., which has been reported for its <em>in vitro</em> anticancer properties. The leaves have traditionally been used for the treatment of inflammation, infections, and diabetes. In this study, a standardized chamuangone-enriched extract (CEE) from <em>G. cowa</em> leaves, containing 73.0 ± 2.0 % w/w of chamuangone, was evaluated <em>in vitro</em> and <em>in vivo</em> in allograft models (4 T1-luc cells) of breast cancer (BC) and metastatic breast cancer (MBC). The effects of CEE on 4 T1-luc cell viability, apoptosis, cell cycle, and cell migration were analyzed using CCK-8, flow cytometry, and wound healing assays. The <em>in vivo</em> antitumor and antimetastatic efficacy of CEE at doses of 25, 50, and 100 mg/kg body weight (b.w.) was evaluated in BALB/c mice. Tumor markers (CEA, CA 125, CA 15–3), apoptotic markers (p53, Bcl-2), and inflammatory markers (MMP-2, MMP-9, IL-6, NF-κB, and TNF-α) were assessed using ELISA assays. Additionally, the pharmacokinetic and biodistribution profiles of CEE were assessed using the normal mice. The results revealed that CEE (10 µg/mL) decreased 4 T1-luc cell viability, with IC<sub>50</sub> values of 62.5, 48.07, and 31.18 μg/mL at 24, 48, and 72 h, respectively. CEE induced early apoptosis (18.38 %) and late apoptosis (42.79 %), inhibited cell migration and triggered cell cycle arrest, with 59.92 % of cells in the subG1 phase. Furthermore, CEE at 100 mg/kg b.w., significantly inhibited tumor growth and metastasis, <em>in vivo</em> and significantly modulating apoptotic, tumor, and inflammatory markers. The plasma half-life (t½) of CEE at 100 mg/kg b.w. was found to be 11 h. The liver achieved the maximum concentration of chamuangone, followed by the spleen, kidneys, lungs, and heart. Based on the preclinical safety assessment of CEE, a green extract, a dose of 100 mg/kg b.w. is considered safe for therapeutic application as a chemopreventive functional ingredient in BC treatment.</div></div>","PeriodicalId":360,"journal":{"name":"Journal of Functional Foods","volume":"127 ","pages":"Article 106730"},"PeriodicalIF":3.8,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628577","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}