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Amentoflavone ameliorates DSS-induced ulcerative colitis via gut microbiota-bile acid metabolism axis modulation
IF 3.8 2区 农林科学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-02-18 DOI: 10.1016/j.jff.2025.106706
Yuting Chen , Kaipeng Li , Meiyan Zhang , Jie Liu , Man Wang , Yuhan Xiu , Qiaoyue Zhang , Ding Zhao
Amentoflavone (AMF) has anti-inflammatory, antibacterial, and antioxidant properties. However, the effect and underlying mechanisms of AMF on ulcerative colitis (UC) are unclear. This study aimed to examine the protective effects and regulatory mechanisms of AMF in UC in rats. AMF alleviates UC by inhibiting the spleen index, relieving colon shortening, reducing the disease activity index and reversing pathological injury of the colon tissue. Through 16 s high-throughput sequencing technology and targeted metabolomics methods, AMF was found to reconstruct intestinal microorganisms and regulate the homeostasis of bile acid metabolites. Additionally, AMF protects intestinal barrier function by activating bile acid receptors (TGR5 and FXR), and regulating tight junction proteins (ZO-1 and occludin). In conclusion, the therapeutic mechanism of AMF is mainly attributed to the activation of the gut microbiota-bile acid axis. These findings contribute to mechanistic research and drug development for AMF intervention in patients with UC.
{"title":"Amentoflavone ameliorates DSS-induced ulcerative colitis via gut microbiota-bile acid metabolism axis modulation","authors":"Yuting Chen ,&nbsp;Kaipeng Li ,&nbsp;Meiyan Zhang ,&nbsp;Jie Liu ,&nbsp;Man Wang ,&nbsp;Yuhan Xiu ,&nbsp;Qiaoyue Zhang ,&nbsp;Ding Zhao","doi":"10.1016/j.jff.2025.106706","DOIUrl":"10.1016/j.jff.2025.106706","url":null,"abstract":"<div><div>Amentoflavone (AMF) has anti-inflammatory, antibacterial, and antioxidant properties. However, the effect and underlying mechanisms of AMF on ulcerative colitis (UC) are unclear. This study aimed to examine the protective effects and regulatory mechanisms of AMF in UC in rats. AMF alleviates UC by inhibiting the spleen index, relieving colon shortening, reducing the disease activity index and reversing pathological injury of the colon tissue. Through 16 s high-throughput sequencing technology and targeted metabolomics methods, AMF was found to reconstruct intestinal microorganisms and regulate the homeostasis of bile acid metabolites. Additionally, AMF protects intestinal barrier function by activating bile acid receptors (TGR5 and FXR), and regulating tight junction proteins (ZO-1 and occludin). In conclusion, the therapeutic mechanism of AMF is mainly attributed to the activation of the gut microbiota-bile acid axis. These findings contribute to mechanistic research and drug development for AMF intervention in patients with UC.</div></div>","PeriodicalId":360,"journal":{"name":"Journal of Functional Foods","volume":"126 ","pages":"Article 106706"},"PeriodicalIF":3.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143429840","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
Ethanol extract of Lactobacillus rhamnosus AC1-fermented soymilk alleviated DSS-induced colitis via LPS-TLR4-NF-κB signaling pathway
IF 3.8 2区 农林科学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-02-14 DOI: 10.1016/j.jff.2025.106704
Haicui Wu , Weijie Fang , Yuqing Lu , Jiachi Chiou
Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder associated with a variety of factors including environmental, genetic, gut flora and immune factors. Our previous studies showed that soymilk fermented by Lactobacillus rhamnosus AC1 harbors anti-inflammatory and antioxidant effects. This study aimed to further investigate the beneficial effects of ethanol extract (EE) of L. rhamnosus AC1-fermented soymilk on dextran sulfate sodium (DSS)-induced colitis mice via LPS-TLR4-NF-κB signaling pathway and improvement of gut microbiota dysbiosis. Low dose of EE (200 mg/kg), high dose of EE (400 mg/kg), and anti-colitis drug, 5-Amino Salicylic Acid (5-ASA, 200 mg/kg), were used as the interventions in DSS-induced acute colitis. EE of L. rhamnosus AC1-fermented soymilk significantly alleviated body weight loss, disease activity index (DAI) scores, and histopathological damage. In addition, EE reduced apoptosis, increased proliferation, alleviated mucosa barrier damage, and down-regulated LPS-TLR4-NF-κB signaling pathway in DSS-induced colitis mice. Furthermore, the gut microbiota dysbiosis induced by DSS treatment was partially restored by EE treatments, especially in Proteobacteria and its lower taxa. In conclusion, the present study demonstrated that EE of L. rhamnosus AC1-fermented soymilk is a promising dietary intervention strategy to prevent DSS-induced colitis through down-regulation of LPS-TLR4-NF-κB signaling pathway and reverting gut microbiota dysbiosis.
{"title":"Ethanol extract of Lactobacillus rhamnosus AC1-fermented soymilk alleviated DSS-induced colitis via LPS-TLR4-NF-κB signaling pathway","authors":"Haicui Wu ,&nbsp;Weijie Fang ,&nbsp;Yuqing Lu ,&nbsp;Jiachi Chiou","doi":"10.1016/j.jff.2025.106704","DOIUrl":"10.1016/j.jff.2025.106704","url":null,"abstract":"<div><div>Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder associated with a variety of factors including environmental, genetic, gut flora and immune factors. Our previous studies showed that soymilk fermented by <em>Lactobacillus rhamnosus</em> AC1 harbors anti-inflammatory and antioxidant effects. This study aimed to further investigate the beneficial effects of ethanol extract (EE) of L. <em>rhamnosus</em> AC1-fermented soymilk on dextran sulfate sodium (DSS)-induced colitis mice via LPS-TLR4-NF-κB signaling pathway and improvement of gut microbiota dysbiosis. Low dose of EE (200 mg/kg), high dose of EE (400 mg/kg), and anti-colitis drug, 5-Amino Salicylic Acid (5-ASA, 200 mg/kg), were used as the interventions in DSS-induced acute colitis. EE of L. <em>rhamnosus</em> AC1-fermented soymilk significantly alleviated body weight loss, disease activity index (DAI) scores, and histopathological damage. In addition, EE reduced apoptosis, increased proliferation, alleviated mucosa barrier damage, and down-regulated LPS-TLR4-NF-κB signaling pathway in DSS-induced colitis mice. Furthermore, the gut microbiota dysbiosis induced by DSS treatment was partially restored by EE treatments, especially in <em>Proteobacteria</em> and its lower taxa. In conclusion, the present study demonstrated that EE of L. <em>rhamnosus</em> AC1-fermented soymilk is a promising dietary intervention strategy to prevent DSS-induced colitis through down-regulation of LPS-TLR4-NF-κB signaling pathway and reverting gut microbiota dysbiosis.</div></div>","PeriodicalId":360,"journal":{"name":"Journal of Functional Foods","volume":"126 ","pages":"Article 106704"},"PeriodicalIF":3.8,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403301","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
Mixed fruits and berries counteract the detrimental effects caused by the obesogenic cafeteria /western diet in adolescent rat model of obesity
IF 3.8 2区 农林科学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-02-14 DOI: 10.1016/j.jff.2025.106693
Rawan Al Hazaimeh, Louis Shackelford, Judith Boateng
The present study determined if mixed fruits and berries (MFB) could alleviate the negative effects of cafeteria (CAF) diet-induced obesity by improving metabolic and inflammatory markers in a preclinical model of adolescent obesity. Adolescent male Sprague Dawley rats were assigned to Chow-Negative Control (NC), CAF-Positive Control (PC), Treatment: 3 % MFB (T1) or 6 % MFB (T2), Prevention: 3 % MFB (P1) or 6 % MFB (P2) + CAF, Intervention: CAF + NC for 4 weeks, then 3 % MFB (I1) or 6 % MFB (I2) for 2 weeks. After 6 weeks, MFB supplementation significantly (p < 0.05) reduced several key anthropometric parameters and improved plasma and serum concentrations of obesity biomarkers(p < 0.05). P and I groups showed smaller adipocyte cell size and number compared to PC and NC groups. Proinflammatory plasma cytokines increased in PC group compared to other groups. Results corroborate our hypothesis that MFB mitigated metabolic syndrome conditions induced by CAF diet.
{"title":"Mixed fruits and berries counteract the detrimental effects caused by the obesogenic cafeteria /western diet in adolescent rat model of obesity","authors":"Rawan Al Hazaimeh,&nbsp;Louis Shackelford,&nbsp;Judith Boateng","doi":"10.1016/j.jff.2025.106693","DOIUrl":"10.1016/j.jff.2025.106693","url":null,"abstract":"<div><div>The present study determined if mixed fruits and berries (MFB) could alleviate the negative effects of cafeteria (CAF) diet-induced obesity by improving metabolic and inflammatory markers in a preclinical model of adolescent obesity. Adolescent male Sprague Dawley rats were assigned to Chow-Negative Control (NC), CAF-Positive Control (PC), Treatment: 3 % MFB (T1) or 6 % MFB (T2), Prevention: 3 % MFB (P1) or 6 % MFB (P2) + CAF, Intervention: CAF + NC for 4 weeks, then 3 % MFB (I1) or 6 % MFB (I2) for 2 weeks. After 6 weeks, MFB supplementation significantly (<em>p</em> &lt; 0.05) reduced several key anthropometric parameters and improved plasma and serum concentrations of obesity biomarkers(p &lt; 0.05). P and I groups showed smaller adipocyte cell size and number compared to PC and NC groups. Proinflammatory plasma cytokines increased in PC group compared to other groups. Results corroborate our hypothesis that MFB mitigated metabolic syndrome conditions induced by CAF diet.</div></div>","PeriodicalId":360,"journal":{"name":"Journal of Functional Foods","volume":"126 ","pages":"Article 106693"},"PeriodicalIF":3.8,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403300","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
The polysaccharides from Hemerocallis citrina Baroni alleviate cognitive impairment in high-fat diet/streptozocin-induced type 2 diabetic mice
IF 3.8 2区 农林科学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-02-12 DOI: 10.1016/j.jff.2025.106701
Xiaoyu Liu , Yazi Wu , Wenjing Jiang , Kexi Ma , Jinkun Du , Jingming Li
Diabetes is a global health crisis linked to cognitive decline and metabolic dysfunctions. Plant-derived polysaccharides are important components for biological functions. This study investigates the beneficial effects of individual polysaccharide components and whole polysaccharide complex extracted from dried flowers of Hemerocallis citrina Baroni (H. citrina) on type 2 diabetes mellitus (T2DM). Polysaccharides (HCPS-1 and HCPS-2) were isolated from the crude polysaccharides of H. citrina (HCPS), accompanied by a preliminary characterization of the structure. Polysaccharides intervention significantly exerted hypoglycemic effect and alleviated liver damage in high-fat diet (HFD)/streptozotocin-induced T2DM mice. Additionally, polysaccharides intervention significantly increased the number entering correct arm in the Y-maze test, indicating alleviated cognitive impairment. Furthermore, polysaccharides treatment improved peripheral glucose levels, and maintained energy supply to the brain through enhancing brain glucose metabolism and boosting mitochondrial respiratory chain complex activities. These results highlight the potential of H. citrina polysaccharide in managing T2DM and related cognitive impairment.
{"title":"The polysaccharides from Hemerocallis citrina Baroni alleviate cognitive impairment in high-fat diet/streptozocin-induced type 2 diabetic mice","authors":"Xiaoyu Liu ,&nbsp;Yazi Wu ,&nbsp;Wenjing Jiang ,&nbsp;Kexi Ma ,&nbsp;Jinkun Du ,&nbsp;Jingming Li","doi":"10.1016/j.jff.2025.106701","DOIUrl":"10.1016/j.jff.2025.106701","url":null,"abstract":"<div><div>Diabetes is a global health crisis linked to cognitive decline and metabolic dysfunctions. Plant-derived polysaccharides are important components for biological functions. This study investigates the beneficial effects of individual polysaccharide components and whole polysaccharide complex extracted from dried flowers of <em>Hemerocallis citrina</em> Baroni (<em>H. citrina</em>) on type 2 diabetes mellitus (T2DM). Polysaccharides (HCPS-1 and HCPS-2) were isolated from the crude polysaccharides of <em>H. citrina</em> (HCPS), accompanied by a preliminary characterization of the structure. Polysaccharides intervention significantly exerted hypoglycemic effect and alleviated liver damage in high-fat diet (HFD)/streptozotocin-induced T2DM mice. Additionally, polysaccharides intervention significantly increased the number entering correct arm in the Y-maze test, indicating alleviated cognitive impairment. Furthermore, polysaccharides treatment improved peripheral glucose levels, and maintained energy supply to the brain through enhancing brain glucose metabolism and boosting mitochondrial respiratory chain complex activities. These results highlight the potential of <em>H. citrina</em> polysaccharide in managing T2DM and related cognitive impairment.</div></div>","PeriodicalId":360,"journal":{"name":"Journal of Functional Foods","volume":"126 ","pages":"Article 106701"},"PeriodicalIF":3.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143386939","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
Antiemetic activity of Sesamol possibly through serotonergic and dopaminergic receptor interaction pathways: In vivo and in silico studies
IF 3.8 2区 农林科学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-02-08 DOI: 10.1016/j.jff.2025.106702
Touhidul Islam Tanim , Ayman M. Al-Qaaneh , Raihan Chowdhury , Md. Shimul Bhuia , Tabassum Islam , Md Showkoth Akbor , Md. Tahajul Islam , Md. Mohasin Miah , Ali Raza Ishaq , Mostafa A. Abdel-Maksoud , Mohamed A. El-Tayeb , Mohamed El-Shazly , Muhammad Torequl Islam , Heba A.S. El-Nashar
Sesamol (SEL) is 3,4-methylenedioxyphenol isolated from sesame seeds. This study aimed to evaluate the antiemetic activity of SEL, supported by in vivo and in silico studies. Further, molecular docking was carried out to understand the molecular interaction between selected ligands and different receptors liable for mediating emesis. SEL (25 and 50 mg/kg) showed dose-dependent elevation in latency (133.20 ± 2.19 and 293.00 ± 5.27 s) and diminishment in the retching number (16.40 ± 1.15 and 9.40 ± 1.04 times), compared to control. Additionally, SEL can antagonize the activity of ondansetron (OND; 5 mg/kg) and domperidone (DOM; 7 mg/kg), resulting in a decrease in latency (256.00 ± 9.59 and 253.00 ± 2.79 s) and enhancing the number of retches (11.80 ± 0.82 and 12.60 ± 1.04) in combination rather than OND and DOM alone. An in-silico study showed SEL has moderate binding activity (−5.9 and − 5.7 kcal/mol) for serotonin (5HT3) and dopaminergic (D2) receptors, respectively, via hydrogen and hydrophobic bonds with specific amino acid residues.
{"title":"Antiemetic activity of Sesamol possibly through serotonergic and dopaminergic receptor interaction pathways: In vivo and in silico studies","authors":"Touhidul Islam Tanim ,&nbsp;Ayman M. Al-Qaaneh ,&nbsp;Raihan Chowdhury ,&nbsp;Md. Shimul Bhuia ,&nbsp;Tabassum Islam ,&nbsp;Md Showkoth Akbor ,&nbsp;Md. Tahajul Islam ,&nbsp;Md. Mohasin Miah ,&nbsp;Ali Raza Ishaq ,&nbsp;Mostafa A. Abdel-Maksoud ,&nbsp;Mohamed A. El-Tayeb ,&nbsp;Mohamed El-Shazly ,&nbsp;Muhammad Torequl Islam ,&nbsp;Heba A.S. El-Nashar","doi":"10.1016/j.jff.2025.106702","DOIUrl":"10.1016/j.jff.2025.106702","url":null,"abstract":"<div><div>Sesamol (SEL) is 3,4-methylenedioxyphenol isolated from sesame seeds. This study aimed to evaluate the antiemetic activity of SEL, supported by <em>in vivo</em> and <em>in silico</em> studies. Further, molecular docking was carried out to understand the molecular interaction between selected ligands and different receptors liable for mediating emesis. SEL (25 and 50 mg/kg) showed dose-dependent elevation in latency (133.20 ± 2.19 and 293.00 ± 5.27 s) and diminishment in the retching number (16.40 ± 1.15 and 9.40 ± 1.04 times), compared to control. Additionally, SEL can antagonize the activity of ondansetron (OND; 5 mg/kg) and domperidone (DOM; 7 mg/kg), resulting in a decrease in latency (256.00 ± 9.59 and 253.00 ± 2.79 s) and enhancing the number of retches (11.80 ± 0.82 and 12.60 ± 1.04) in combination rather than OND and DOM alone. An <em>in-silico</em> study showed SEL has moderate binding activity (−5.9 and − 5.7 kcal/mol) for serotonin (5HT<sub>3</sub>) and dopaminergic (D<sub>2</sub>) receptors, respectively, <em>via</em> hydrogen and hydrophobic bonds with specific amino acid residues.</div></div>","PeriodicalId":360,"journal":{"name":"Journal of Functional Foods","volume":"126 ","pages":"Article 106702"},"PeriodicalIF":3.8,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143372304","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
PLGA-based biocompatible nanoparticles improved anti-breast tumor efficacy of 1,25(OH)2D3 through the SOCS3/STAT3/EMT signaling axis
IF 3.8 2区 农林科学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-02-07 DOI: 10.1016/j.jff.2025.106700
JinJing Pan , Ping Wang , Linghong Xiong , Wenqing Yang , Jie Li , Kai Yang , Bingyan Li
Several studies have demonstrated that active vitamin D (1,25(OH)2D3) can impede the cancerous traits of breast cancer. However, due to the susceptibility of 1,25(OH)2D3 to degradation in the tumor microenvironment, higher doses were required to sustain its efficacy. This elevated dosage could lead to significant side effects, thereby constraining its practical application in clinical settings. The FDA-approved nanomaterial poly (lactic-co-glycolic acid) (PLGA) had the potential for utilization in clinical settings. It could be employed to helps in maintaining and extending the biological activity of the drugs, thereby enhancing their therapeutic efficacy. Hence, the potential of PLGA encapsulation to augment the anti-breast cancer properties of 1,25(OH)2D3 and the underlying mechanism remain uncertain. In this study, our findings not only demonstrated the effective encapsulation of 1,25(OH)2D3 in PLGA (PLGA-1,25(OH)2D3, PD) but also indicated that the PD has a more potent inhibitory effect on the proliferation and migration of breast cancer cells compared with 1,25(OH)2D3 alone. Consistently, PD exhibits superior efficacy in suppressing subcutaneous neoplasia and lung metastasis of breast cancer cells compared to 1,25(OH)2D3. It is noteworthy that PD significantly alleviates the adverse effects of increased serum calcium levels and weight loss in mice induced by 1,25(OH)2D3. Subsequently, bioinformatics analysis and western blot confirmed that PD showed a more pronounced upregulation of SOCS3 and a concurrent downregulation of JAK/STAT3 and PI3K/AKT signals compared to 1,25(OH)2D3 both in vivo and in vitro. Considering that epithelial-mesenchymal transition (EMT) is downstream of the SOCS3/STAT3/PI3K pathway, our findings also revealed that 1,25(OH)2D3 markedly regulated the expression of EMT markers. Additionally, the inhibitor of STAT3 exhibited inhibitory effects on EMT progression in breast cancer cells. Moreover, we manifested that PD robustly curtailed the EMT markers compared to 1,25(OH)2D3 in vivo. In conclusion, these findings elucidate PLGA-1,25(OH)2D3 enhances 1,25(OH)2D3's antitumor effects through the SOCS3/STAT3/EMT signaling axis, offering potential targets for therapeutic interventions in breast cancer treatment.
{"title":"PLGA-based biocompatible nanoparticles improved anti-breast tumor efficacy of 1,25(OH)2D3 through the SOCS3/STAT3/EMT signaling axis","authors":"JinJing Pan ,&nbsp;Ping Wang ,&nbsp;Linghong Xiong ,&nbsp;Wenqing Yang ,&nbsp;Jie Li ,&nbsp;Kai Yang ,&nbsp;Bingyan Li","doi":"10.1016/j.jff.2025.106700","DOIUrl":"10.1016/j.jff.2025.106700","url":null,"abstract":"<div><div>Several studies have demonstrated that active vitamin D (1,25(OH)<sub>2</sub>D<sub>3</sub>) can impede the cancerous traits of breast cancer. However, due to the susceptibility of 1,25(OH)<sub>2</sub>D<sub>3</sub> to degradation in the tumor microenvironment, higher doses were required to sustain its efficacy. This elevated dosage could lead to significant side effects, thereby constraining its practical application in clinical settings. The FDA-approved nanomaterial poly (lactic-<em>co</em>-glycolic acid) (PLGA) had the potential for utilization in clinical settings. It could be employed to helps in maintaining and extending the biological activity of the drugs, thereby enhancing their therapeutic efficacy. Hence, the potential of PLGA encapsulation to augment the anti-breast cancer properties of 1,25(OH)<sub>2</sub>D<sub>3</sub> and the underlying mechanism remain uncertain. In this study, our findings not only demonstrated the effective encapsulation of 1,25(OH)<sub>2</sub>D<sub>3</sub> in PLGA (PLGA-1,25(OH)<sub>2</sub>D<sub>3</sub>, PD) but also indicated that the PD has a more potent inhibitory effect on the proliferation and migration of breast cancer cells compared with 1,25(OH)<sub>2</sub>D<sub>3</sub> alone. Consistently, PD exhibits superior efficacy in suppressing subcutaneous neoplasia and lung metastasis of breast cancer cells compared to 1,25(OH)<sub>2</sub>D<sub>3</sub>. It is noteworthy that PD significantly alleviates the adverse effects of increased serum calcium levels and weight loss in mice induced by 1,25(OH)<sub>2</sub>D<sub>3</sub>. Subsequently, bioinformatics analysis and western blot confirmed that PD showed a more pronounced upregulation of SOCS3 and a concurrent downregulation of JAK/STAT3 and PI3K/AKT signals compared to 1,25(OH)<sub>2</sub>D<sub>3</sub> both <em>in vivo</em> and <em>in vitro</em>. Considering that epithelial-mesenchymal transition (EMT) is downstream of the SOCS3/STAT3/PI3K pathway, our findings also revealed that 1,25(OH)<sub>2</sub>D<sub>3</sub> markedly regulated the expression of EMT markers. Additionally, the inhibitor of STAT3 exhibited inhibitory effects on EMT progression in breast cancer cells. Moreover, we manifested that PD robustly curtailed the EMT markers compared to 1,25(OH)<sub>2</sub>D<sub>3</sub> <em>in vivo.</em> In conclusion, these findings elucidate PLGA-1,25(OH)<sub>2</sub>D<sub>3</sub> enhances 1,25(OH)<sub>2</sub>D<sub>3</sub>'s antitumor effects through the SOCS3/STAT3/EMT signaling axis, offering potential targets for therapeutic interventions in breast cancer treatment.</div></div>","PeriodicalId":360,"journal":{"name":"Journal of Functional Foods","volume":"126 ","pages":"Article 106700"},"PeriodicalIF":3.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143278625","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
Astragaloside IV inhibits atherosclerosis caused by ferritin autophagy in a lipid deposition environment by activating Nrf2
IF 3.8 2区 农林科学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-02-05 DOI: 10.1016/j.jff.2025.106695
Dandan Liu , Hewei Qin , Guanghua Liu , Yang Gao , Yu Guo
The Chinese medicine Astragalus mongholicus Bunge has the effect of benefiting vital energy and activating blood circulation, and is commonly used clinically in the treatment of various cardiovascular diseases. Astragalus is not only a kind of traditional Chinese medicine, but is now also widely used in various kinds of health food. Astragaloside IV is the most abundant active ingredient in this herb. In addition, astragaloside IV has lipid-modulating and antioxidant pharmacological potential. The vasoprotective and anti-ferroptosis effects of astragaloside IV were determined by establishing a high-fat-fed ApoE−/− mouse model of AS and an ox-LDL-induced model of lipid damage in VECs. Lipid profile (TC, TG, LDL-C, HDLC), HE and local oil red O showed a reduction in atherosclerotic pathological damage and lipid deposition after astragaloside IV treatment. Astragaloside IV was then able to increase FTH1 and p62 expression, decrease NCOA4 and Beclin1 expression, and inhibit ferritin autophagy by activating Nrf2. Meanwhile, when ML385 inhibits Nrf2, astragaloside IV can diminish the expression of divalent iron, suppress iron death-related factors (FTH1, FTL, FPN, ACSL4), and alleviate disorders in iron metabolism and the overproduction of ROS. Collectively, these findings suggest that astragaloside IV can regulate autophagy-dependent NCOA4 and FTH1 expression through activation of Nrf2, thereby inhibiting autophagy.
中药黄芪具有益气活血的功效,临床上常用于治疗各种心血管疾病。黄芪不仅是一种中药,现在还被广泛应用于各种保健食品中。黄芪皂苷 IV 是黄芪中含量最高的有效成分。此外,黄芪皂苷 IV 还具有调节血脂和抗氧化的药理潜力。通过建立高脂喂养载脂蛋白E-/-小鼠强直性脊柱炎模型和氧化-LDL诱导的血管内皮细胞脂质损伤模型,确定了黄芪皂苷 IV 的血管保护和抗软化作用。血脂谱(TC、TG、LDL-C、HDLC)、HE和局部油红O显示,黄芪皂苷IV治疗后动脉粥样硬化病理损伤和脂质沉积减少。黄芪皂苷 IV 还能增加 FTH1 和 p62 的表达,降低 NCOA4 和 Beclin1 的表达,并通过激活 Nrf2 抑制铁蛋白自噬。同时,当 ML385 抑制 Nrf2 时,黄芪皂苷 IV 可减少二价铁的表达,抑制铁死亡相关因子(FTH1、FTL、FPN、ACSL4),缓解铁代谢紊乱和 ROS 过度产生。总之,这些研究结果表明,黄芪皂苷 IV 可以通过激活 Nrf2 来调节依赖于自噬的 NCOA4 和 FTH1 的表达,从而抑制自噬。
{"title":"Astragaloside IV inhibits atherosclerosis caused by ferritin autophagy in a lipid deposition environment by activating Nrf2","authors":"Dandan Liu ,&nbsp;Hewei Qin ,&nbsp;Guanghua Liu ,&nbsp;Yang Gao ,&nbsp;Yu Guo","doi":"10.1016/j.jff.2025.106695","DOIUrl":"10.1016/j.jff.2025.106695","url":null,"abstract":"<div><div>The Chinese medicine <em>Astragalus mongholicus</em> Bunge has the effect of benefiting vital energy and activating blood circulation, and is commonly used clinically in the treatment of various cardiovascular diseases. Astragalus is not only a kind of traditional Chinese medicine, but is now also widely used in various kinds of health food. Astragaloside IV is the most abundant active ingredient in this herb. In addition, astragaloside IV has lipid-modulating and antioxidant pharmacological potential. The vasoprotective and anti-ferroptosis effects of astragaloside IV were determined by establishing a high-fat-fed ApoE<sup>−/−</sup> mouse model of AS and an ox-LDL-induced model of lipid damage in VECs. Lipid profile (TC, TG, LDL-C, HDL<img>C), HE and local oil red O showed a reduction in atherosclerotic pathological damage and lipid deposition after astragaloside IV treatment. Astragaloside IV was then able to increase FTH1 and p62 expression, decrease NCOA4 and Beclin1 expression, and inhibit ferritin autophagy by activating Nrf2. Meanwhile, when ML385 inhibits Nrf2, astragaloside IV can diminish the expression of divalent iron, suppress iron death-related factors (FTH1, FTL, FPN, ACSL4), and alleviate disorders in iron metabolism and the overproduction of ROS. Collectively, these findings suggest that astragaloside IV can regulate autophagy-dependent NCOA4 and FTH1 expression through activation of Nrf2, thereby inhibiting autophagy.</div></div>","PeriodicalId":360,"journal":{"name":"Journal of Functional Foods","volume":"126 ","pages":"Article 106695"},"PeriodicalIF":3.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143182033","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
Golden berry fruit modulates inflammation in LPS-stimulated RAW 264.7 macrophages and the DSS-induced acute colitis model
IF 3.8 2区 农林科学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.jff.2025.106665
Jenny Castro , Guillermo Lopez-Lluch , Juan Carlos Rodríguez , Rocío de la Puerta , Lía Barrios , Rubén Salas , Luis Franco
Physalis peruviana L. (golden berry) fruit is attractive for its many health benefits, associated with the presence of anti-inflammatory and antioxidant compounds. High fruit consumption has been associated with a lower risk of developing chronic non-communicable diseases. This work evaluated the anti-inflammatory potential of ten fruits cultivated in Colombia, determining their capacity to inhibit ⋅NO production in LPS-activated RAW 264.7 macrophages. The most active extracts were evaluated for their effect on the production of IL-1β, IL-6, TNF-α, and PGE2. Golden berry was the most active extract, so its immunomodulatory effect was evaluated in a model of DSS-induced colitis in BALB/c mice. Dietary supplementation with golden berry attenuates the pathological symptoms of colitis. This effect may be associated with the inhibition of neutrophil infiltration and impacts on the production of IL-6, IL-1β, IL-10, TNF-α, and ROS. Our results suggest that consistently consuming golden berries could benefit intestinal inflammation.
{"title":"Golden berry fruit modulates inflammation in LPS-stimulated RAW 264.7 macrophages and the DSS-induced acute colitis model","authors":"Jenny Castro ,&nbsp;Guillermo Lopez-Lluch ,&nbsp;Juan Carlos Rodríguez ,&nbsp;Rocío de la Puerta ,&nbsp;Lía Barrios ,&nbsp;Rubén Salas ,&nbsp;Luis Franco","doi":"10.1016/j.jff.2025.106665","DOIUrl":"10.1016/j.jff.2025.106665","url":null,"abstract":"<div><div><em>Physalis peruviana</em> L. (golden berry) fruit is attractive for its many health benefits, associated with the presence of anti-inflammatory and antioxidant compounds. High fruit consumption has been associated with a lower risk of developing chronic non-communicable diseases. This work evaluated the anti-inflammatory potential of ten fruits cultivated in Colombia, determining their capacity to inhibit ⋅NO production in LPS-activated RAW 264.7 macrophages. The most active extracts were evaluated for their effect on the production of IL-1β, IL-6, TNF-α, and PGE2. Golden berry was the most active extract, so its immunomodulatory effect was evaluated in a model of DSS-induced colitis in BALB/c mice. Dietary supplementation with golden berry attenuates the pathological symptoms of colitis. This effect may be associated with the inhibition of neutrophil infiltration and impacts on the production of IL-6, IL-1β, IL-10, TNF-α, and ROS. Our results suggest that consistently consuming golden berries could benefit intestinal inflammation.</div></div>","PeriodicalId":360,"journal":{"name":"Journal of Functional Foods","volume":"125 ","pages":"Article 106665"},"PeriodicalIF":3.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143183685","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
L-arabinose alleviates constipation through gastrointestinal peptide,gut microbiota,and Phlpp2 of gastrointestinal rhythms in rats
IF 3.8 2区 农林科学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.jff.2025.106697
Ting Gong , Linzheng Liao , Yong Tang , Weiwei Liu , Ling Yao , Zhen Wu , Jianmei Li , Fulai Bai , Qian Zhang , Liling Tang
Constipation is a common gastrointestinal disorder, and while L-arabinose has been shown to relieve it, the exact molecular mechanisms remain unclear. This study investigated the effects of L-arabinose in constipated rat at doses of 400, 600, and 800 mg/kg body weight (B.W.). The 800 mg/kg B.W. dose significantly improved overall physiological state, stool consistency, intestinal transit, and gastric emptying. It also improved gastric, liver, and kidney function, while modulating key gastrointestinal peptides, including motilin (MTL), substance P (SP), vasoactive intestinal peptide (VIP), acetylcholinesterase (AchE), endothelin-1 (ET-1), serotonin (5-HT), somatostatin (SS), gastrin (Gas), and nitric oxide (NO). In addition, the 800 mg/kg dose notably increased goblet cell numbers, mucus layer thickness, and beneficial gut microbes such as Ruminococcus flavefaciens and Muribaculum intestinale. It also upregulated the expression of Cd38, Phlpp2, Muc3, and Acat2, while downregulating Cd34, C1qa, and C1qc. These results indicate that L-arabinose not only alleviates constipation but also enhances immune function and regulates signaling pathways, restoring gastrointestinal peptides to near-normal levels.
{"title":"L-arabinose alleviates constipation through gastrointestinal peptide,gut microbiota,and Phlpp2 of gastrointestinal rhythms in rats","authors":"Ting Gong ,&nbsp;Linzheng Liao ,&nbsp;Yong Tang ,&nbsp;Weiwei Liu ,&nbsp;Ling Yao ,&nbsp;Zhen Wu ,&nbsp;Jianmei Li ,&nbsp;Fulai Bai ,&nbsp;Qian Zhang ,&nbsp;Liling Tang","doi":"10.1016/j.jff.2025.106697","DOIUrl":"10.1016/j.jff.2025.106697","url":null,"abstract":"<div><div>Constipation is a common gastrointestinal disorder, and while L-arabinose has been shown to relieve it, the exact molecular mechanisms remain unclear. This study investigated the effects of L-arabinose in constipated rat at doses of 400, 600, and 800 mg/kg body weight (B.W.). The 800 mg/kg B.W. dose significantly improved overall physiological state, stool consistency, intestinal transit, and gastric emptying. It also improved gastric, liver, and kidney function, while modulating key gastrointestinal peptides, including motilin (MTL), substance P (SP), vasoactive intestinal peptide (VIP), acetylcholinesterase (AchE), endothelin-1 (ET-1), serotonin (5-HT), somatostatin (SS), gastrin (Gas), and nitric oxide (NO). In addition, the 800 mg/kg dose notably increased goblet cell numbers, mucus layer thickness, and beneficial gut microbes such as <em>Ruminococcus flavefaciens</em> and <em>Muribaculum intestinale</em>. It also upregulated the expression of <em>Cd38, Phlpp2, Muc3,</em> and <em>Acat2</em>, while downregulating <em>Cd34</em>, <em>C1qa</em>, and <em>C1qc.</em> These results indicate that L-arabinose not only alleviates constipation but also enhances immune function and regulates signaling pathways, restoring gastrointestinal peptides to near-normal levels.</div></div>","PeriodicalId":360,"journal":{"name":"Journal of Functional Foods","volume":"125 ","pages":"Article 106697"},"PeriodicalIF":3.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143182962","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
Protective effects and antioxidant mechanisms of lactobacillus combined with carnosine on the stomach and small intestine
IF 3.8 2区 农林科学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.jff.2025.106687
Jian Qin , Ziyi Luo , Xu Yang , Yunqing Zhang , Huiying Li , Conghui Wang , Zhiqiang Zou , Yue Ma , Jing Ma , Daoyou Yue , Dipeng Zhao , Sen Qin , Rong Du
Oxidative stress is intricately related to gastrointestinal diseases. Although both lactobacillus (LAB) and carnosine (CAR) contribute to combating oxidative stress and attenuating gastrointestinal disorders, little is known about the effects and mechanisms of their combined treatment. Here, we report the protective effects of LAB and/or CAR on the gastrointestinal tissues in normal or dexamethasone (Dex)-induced stress mice. The combination of LAB and CAR protected the structures of stomach and small intestine, alleviating the Dex-induced tissue damages. Additionally, this combined treatment increased the activity of antioxidant enzymes and up-regulated the expression of antioxidant genes in the Nrf2 signaling pathway in stress mice. Our study sheds light on the synergetic and complementary roles of LAB and CAR in maintaining the structural and functional integrity of stomach and small intestine, offering clues for understanding the regulation of antioxidant enzyme genes through the Nrf2 pathway as a potential mechanism.
氧化应激与胃肠道疾病密切相关。虽然乳酸菌(LAB)和肌肽(CAR)都有助于对抗氧化应激和减轻胃肠道疾病,但人们对它们联合治疗的效果和机制知之甚少。在此,我们报告了 LAB 和/或 CAR 对正常或地塞米松(Dex)诱导的应激小鼠胃肠道组织的保护作用。LAB 和 CAR 的联合治疗保护了胃和小肠的结构,减轻了地塞米松引起的组织损伤。此外,这种联合疗法还提高了应激小鼠体内抗氧化酶的活性,并上调了Nrf2信号通路中抗氧化基因的表达。我们的研究揭示了LAB和CAR在维持胃和小肠的结构和功能完整性方面的协同和互补作用,为了解通过Nrf2途径调控抗氧化酶基因的潜在机制提供了线索。
{"title":"Protective effects and antioxidant mechanisms of lactobacillus combined with carnosine on the stomach and small intestine","authors":"Jian Qin ,&nbsp;Ziyi Luo ,&nbsp;Xu Yang ,&nbsp;Yunqing Zhang ,&nbsp;Huiying Li ,&nbsp;Conghui Wang ,&nbsp;Zhiqiang Zou ,&nbsp;Yue Ma ,&nbsp;Jing Ma ,&nbsp;Daoyou Yue ,&nbsp;Dipeng Zhao ,&nbsp;Sen Qin ,&nbsp;Rong Du","doi":"10.1016/j.jff.2025.106687","DOIUrl":"10.1016/j.jff.2025.106687","url":null,"abstract":"<div><div>Oxidative stress is intricately related to gastrointestinal diseases. Although both lactobacillus (LAB) and carnosine (CAR) contribute to combating oxidative stress and attenuating gastrointestinal disorders, little is known about the effects and mechanisms of their combined treatment. Here, we report the protective effects of LAB and/or CAR on the gastrointestinal tissues in normal or dexamethasone (Dex)-induced stress mice. The combination of LAB and CAR protected the structures of stomach and small intestine, alleviating the Dex-induced tissue damages. Additionally, this combined treatment increased the activity of antioxidant enzymes and up-regulated the expression of antioxidant genes in the Nrf2 signaling pathway in stress mice. Our study sheds light on the synergetic and complementary roles of LAB and CAR in maintaining the structural and functional integrity of stomach and small intestine, offering clues for understanding the regulation of antioxidant enzyme genes through the Nrf2 pathway as a potential mechanism.</div></div>","PeriodicalId":360,"journal":{"name":"Journal of Functional Foods","volume":"125 ","pages":"Article 106687"},"PeriodicalIF":3.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143183058","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
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Journal of Functional Foods
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