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}
Pub Date : 2025-03-15DOI: 10.1016/j.jff.2025.106723
Young Sook Kim , Eunjung Son , Seung-Hyung Kim , Su Hyun Yu , Kyu-Suk Shim , Dong-Seon Kim
This study investigates the mechanisms involved and the effects of an ethanol extract of Glycine soja (GS-E) on inhibition of muscle atrophy and inflammation in a rat model of sciatic nerve (SN) injury and C2C12 myoblast. GS extracts had protective effects on oxidative stress and dexamethasone-induced decrease in cell viability in C2C12 myoblasts by inhibiting the expression of MuRF1, Atragin-1, and Myostatin mRNAs. Rats were divided into normal control group, sciatic nerve injury group, and treatment groups (GS-E at 150 mg/kg, 300 mg/kg, and oxymetholone at 20 mg/kg group). The SN injury group showed a decrease in grip strength and time, while the GS-E group showed a significant dose-dependent increase. Inflammatory factors (TNF-a, IL-b1, IL-6) were significantly reduced in the GS-E–treated SN injury group compared with the SN injury group. The study results suggest that GS-E effectively improved muscle strength by inhibiting muscle atrophy and inflammatory factors.
{"title":"Glycine soja extract alleviates muscle atrophy and inflammatory factors in sciatic nerve injury rats and prevents protein degradation in C2C12 myoblasts","authors":"Young Sook Kim , Eunjung Son , Seung-Hyung Kim , Su Hyun Yu , Kyu-Suk Shim , Dong-Seon Kim","doi":"10.1016/j.jff.2025.106723","DOIUrl":"10.1016/j.jff.2025.106723","url":null,"abstract":"<div><div>This study investigates the mechanisms involved and the effects of an ethanol extract of <em>Glycine soja</em> (GS-E) on inhibition of muscle atrophy and inflammation in a rat model of sciatic nerve (SN) injury and C2C12 myoblast. GS extracts had protective effects on oxidative stress and dexamethasone-induced decrease in cell viability in C2C12 myoblasts by inhibiting the expression of MuRF1, Atragin-1, and Myostatin mRNAs. Rats were divided into normal control group, sciatic nerve injury group, and treatment groups (GS-E at 150 mg/kg, 300 mg/kg, and oxymetholone at 20 mg/kg group). The SN injury group showed a decrease in grip strength and time, while the GS-E group showed a significant dose-dependent increase. Inflammatory factors (TNF-a, IL-b1, IL-6) were significantly reduced in the GS-E–treated SN injury group compared with the SN injury group. The study results suggest that GS-E effectively improved muscle strength by inhibiting muscle atrophy and inflammatory factors.</div></div>","PeriodicalId":360,"journal":{"name":"Journal of Functional Foods","volume":"127 ","pages":"Article 106723"},"PeriodicalIF":3.8,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628575","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 : 2025-03-14DOI: 10.1016/j.jff.2025.106722
Feng Yang , Zhiyuan Wu , Jiandong Gao
Sinapic acid (SA) is a compound widely found in plants, known for its anti-inflammatory, antioxidant, and renal protective effects. This study combined network pharmacology, RNA sequencing, and both in vivo and in vitro experiments to explore the therapeutic effects and mechanisms of SA in hyperuricemia (HUA) mice. SA (50 mg/kg, 100 mg/kg) showed no toxicity in mice. Both SA and U0126–EtOH (MEK1/2 inhibitor) effectively reduced serum uric acid levels in HUA mice, alleviated kidney dysfunction, mitigated renal damage, inhibited ROS production in the kidneys, reduced the expression of MDA, IL-1β, and IL-6, and promoted SOD secretion. Molecular docking showed strong binding of SA to key targets. Western blot and PCR analyses revealed that SA inhibited p-ERK, Bax, and Caspase3 expression, while promoting Bcl-2 expression. Overall, SA alleviates HUA-induced renal injury by inhibiting p-ERK1/2 signaling and apoptosis in renal tubular epithelial cells, offering clinical application for uric acid-lowering therapy.
{"title":"Sinapic acid alleviates kidney injury of hyperuricemia mice by inhibiting ERK1/2-mediated apoptosis of renal tubular epithelial cells","authors":"Feng Yang , Zhiyuan Wu , Jiandong Gao","doi":"10.1016/j.jff.2025.106722","DOIUrl":"10.1016/j.jff.2025.106722","url":null,"abstract":"<div><div>Sinapic acid (SA) is a compound widely found in plants, known for its anti-inflammatory, antioxidant, and renal protective effects. This study combined network pharmacology, RNA sequencing, and both in vivo and in vitro experiments to explore the therapeutic effects and mechanisms of SA in hyperuricemia (HUA) mice. SA (50 mg/kg, 100 mg/kg) showed no toxicity in mice. Both SA and U0126–EtOH (MEK1/2 inhibitor) effectively reduced serum uric acid levels in HUA mice, alleviated kidney dysfunction, mitigated renal damage, inhibited ROS production in the kidneys, reduced the expression of MDA, IL-1β, and IL-6, and promoted SOD secretion. Molecular docking showed strong binding of SA to key targets. Western blot and PCR analyses revealed that SA inhibited p-ERK, Bax, and Caspase3 expression, while promoting Bcl-2 expression. Overall, SA alleviates HUA-induced renal injury by inhibiting p-ERK1/2 signaling and apoptosis in renal tubular epithelial cells, offering clinical application for uric acid-lowering therapy.</div></div>","PeriodicalId":360,"journal":{"name":"Journal of Functional Foods","volume":"127 ","pages":"Article 106722"},"PeriodicalIF":3.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619582","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 : 2025-03-14DOI: 10.1016/j.jff.2025.106725
Jinyi Zhou , Xianli Liu , Lishuang Zhao , Chen Yang , Rong Wang , Li Sun , Lan Luo , Zhimin Yin
Diabetic cataract (DC) is a leading cause of blindness globally. Vision impairment in diabetic individuals frequently necessitates surgical intervention for treatment. However, postoperative inflammation response is the major cause of surgery failure. γ-glutamylcysteine (γ-GC), a direct precursor for glutathione (GSH) biosynthesis, has been reported to prevent diabetes. Here, we sought to explore the effects of γ-GC on high glucose (HG)-induced lens epithelial cells (LECs) oxidative damage and cataract formation. Our findings indicated that γ-GC inhibited the onset and progression of cataract in db/db mice. Meanwhile, HLE cells showed severe oxidative damages after HG stimulation; however, γ-GC could significantly rescue HLE cells from oxidative damage-induced apoptosis and inflammation. We further found that γ-GC could inhibit AKR1B1-mediated epithelial-mesenchymal transition (EMT) to ameliorate DC through regulating TGF-β2/Smad/AKT and AMPK-related signaling. Collectively, γ-GC, as a safe and effective natural dipeptide, emerges as a promising candidate for preventing and treating cataract in diabetic patients.
{"title":"γ-Glutamylcysteine suppresses epithelial-mesenchymal transition in lens epithelial cells to ameliorate diabetic cataract through regulating TGF-β2 and AMPK-related signaling pathways","authors":"Jinyi Zhou , Xianli Liu , Lishuang Zhao , Chen Yang , Rong Wang , Li Sun , Lan Luo , Zhimin Yin","doi":"10.1016/j.jff.2025.106725","DOIUrl":"10.1016/j.jff.2025.106725","url":null,"abstract":"<div><div>Diabetic cataract (DC) is a leading cause of blindness globally. Vision impairment in diabetic individuals frequently necessitates surgical intervention for treatment. However, postoperative inflammation response is the major cause of surgery failure. γ-glutamylcysteine (γ-GC), a direct precursor for glutathione (GSH) biosynthesis, has been reported to prevent diabetes. Here, we sought to explore the effects of γ-GC on high glucose (HG)-induced lens epithelial cells (LECs) oxidative damage and cataract formation. Our findings indicated that γ-GC inhibited the onset and progression of cataract in db/db mice. Meanwhile, HLE cells showed severe oxidative damages after HG stimulation; however, γ-GC could significantly rescue HLE cells from oxidative damage-induced apoptosis and inflammation. We further found that γ-GC could inhibit AKR1B1-mediated epithelial-mesenchymal transition (EMT) to ameliorate DC through regulating TGF-β2/Smad/AKT and AMPK-related signaling. Collectively, γ-GC, as a safe and effective natural dipeptide, emerges as a promising candidate for preventing and treating cataract in diabetic patients.</div></div>","PeriodicalId":360,"journal":{"name":"Journal of Functional Foods","volume":"127 ","pages":"Article 106725"},"PeriodicalIF":3.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619583","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 : 2025-03-13DOI: 10.1016/j.jff.2025.106718
Shuxiao Chen , Pei Qiu , Xincheng Zhou , Xian Yang , Cong Bi , Siyuan Li , Weikang Su , Yunlong Pan , Weihua Tao , Xuejun Wu , Shiqi Jia
Abdominal aortic aneurysm (AAA) is a life-threatening disease. Chronic inflammation plays a crucial role in the pathogenesis of AAA. Akkermansia muciniphila (A. muciniphila) is increasingly recognized for its significant probiotic benefits across various diseases. The objective of this study was to explore the role of A. muciniphila in AAA development. We constructed an AAA model by incubating porcine pancreatic elastase (PPE) with infrarenal abdominal aorta in C57BL/6J mice, and the treatment of A. muciniphila was performed by gavage daily for the next 14 days. Our findings revealed that A. muciniphila reduced the incidence of AAA by decreasing extracellular matrix degradation and mitigating inflammatory response. Mechanistically, A. muciniphila reversed the increased levels of Toll-like receptor 4 (TLR4) and the phospho-p65/p65 of the NF-κB family in the AAA model. Overall, A. muciniphila attenuated AAA progression partially via the TLR4/NF-κB signaling pathway, which held promise as a therapeutic agent for AAA.
{"title":"Akkermansia muciniphila exerts a protective effect on the development of abdominal aortic aneurysm by inhibiting inflammation","authors":"Shuxiao Chen , Pei Qiu , Xincheng Zhou , Xian Yang , Cong Bi , Siyuan Li , Weikang Su , Yunlong Pan , Weihua Tao , Xuejun Wu , Shiqi Jia","doi":"10.1016/j.jff.2025.106718","DOIUrl":"10.1016/j.jff.2025.106718","url":null,"abstract":"<div><div>Abdominal aortic aneurysm (AAA) is a life-threatening disease. Chronic inflammation plays a crucial role in the pathogenesis of AAA. <em>Akkermansia muciniphila</em> (<em>A. muciniphila</em>) is increasingly recognized for its significant probiotic benefits across various diseases. The objective of this study was to explore the role of <em>A. muciniphila</em> in AAA development. We constructed an AAA model by incubating porcine pancreatic elastase (PPE) with infrarenal abdominal aorta in C57BL/6J mice, and the treatment of <em>A. muciniphila</em> was performed by gavage daily for the next 14 days. Our findings revealed that <em>A. muciniphila</em> reduced the incidence of AAA by decreasing extracellular matrix degradation and mitigating inflammatory response. Mechanistically, <em>A. muciniphila</em> reversed the increased levels of Toll-like receptor 4 (TLR4) and the phospho-p65/p65 of the NF-κB family in the AAA model. Overall, <em>A. muciniphila</em> attenuated AAA progression partially via the TLR4/NF-κB signaling pathway, which held promise as a therapeutic agent for AAA.</div></div>","PeriodicalId":360,"journal":{"name":"Journal of Functional Foods","volume":"127 ","pages":"Article 106718"},"PeriodicalIF":3.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610605","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 : 2025-03-13DOI: 10.1016/j.jff.2025.106721
Mihi Yang , Yang Sueun Lee , Un Jae Lee , Seul Kim , Chang-Young Jang , Jung Min Bae , Kyung Bae Lee , Kwang Eun Yeo , Sang Hoon Park
Korean pears and Chlorella have shown potential in detoxifying various xenobiotics. Thus, we investigated their combined effects on the detoxification of endocrine-disrupting chemicals (EDCs), and EDC-related fat and muscle health using a non-inferiority clinical trial and in vivo and in vitro tests. The human doses of pear extracts, chlorella, and positive control (l-carnitine tartrate) were safe levels, based on previous clinical trials and the approvement by Korean government. The combination increased hand grip strength. Total cholesterol, low-density lipoprotein, apoA-I, and apoB levels were alleviated by the combination, which also modulated ACC, FASN, and HSL to affect fatty acid synthesis and lipidosis or β-oxidation in high-fat-diet- and bisphenol-A-treated mice and in 3 T3-L1 adipocytes. Consistently, in vitro experiments showed that the combination treatment suppressed adipocyte differentiation, downregulated PPARγ expression, promoted lipid breakdown, and enhanced myoblast differentiation. In conclusion, the combination can be useful to prevent from EDCs on fat and muscle health.
{"title":"Effects of the combination of Korean pears and chlorella on endocrine-disrupting chemicals and fat and muscle health","authors":"Mihi Yang , Yang Sueun Lee , Un Jae Lee , Seul Kim , Chang-Young Jang , Jung Min Bae , Kyung Bae Lee , Kwang Eun Yeo , Sang Hoon Park","doi":"10.1016/j.jff.2025.106721","DOIUrl":"10.1016/j.jff.2025.106721","url":null,"abstract":"<div><div>Korean pears and <em>Chlorella</em> have shown potential in detoxifying various xenobiotics. Thus, we investigated their combined effects on the detoxification of endocrine-disrupting chemicals (EDCs), and EDC-related fat and muscle health using a non-inferiority clinical trial and in vivo and in vitro tests. The human doses of pear extracts, chlorella, and positive control (<span>l</span>-carnitine tartrate) were safe levels, based on previous clinical trials and the approvement by Korean government. The combination increased hand grip strength. Total cholesterol, low-density lipoprotein, apoA-I, and apoB levels were alleviated by the combination, which also modulated <em>ACC, FASN,</em> and <em>HSL</em> to affect fatty acid synthesis and lipidosis or β-oxidation in high-fat-diet- and bisphenol-A-treated mice and in 3 T3-L1 adipocytes. Consistently, in vitro experiments showed that the combination treatment suppressed adipocyte differentiation, downregulated PPARγ expression, promoted lipid breakdown, and enhanced myoblast differentiation. In conclusion, the combination can be useful to prevent from EDCs on fat and muscle health.</div></div>","PeriodicalId":360,"journal":{"name":"Journal of Functional Foods","volume":"127 ","pages":"Article 106721"},"PeriodicalIF":3.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610604","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}
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