Molecular Nutrition & Food Research最新文献

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Aged Garlic Extract Attenuates CaCl2-Induced Abdominal Aortic Aneurysm Formation by Inhibiting Matrix Metalloproteinase 9 Expression in Macrophages 陈年大蒜提取物通过抑制巨噬细胞中基质金属蛋白酶9的表达来减弱cacl2诱导的腹主动脉瘤形成
IF 4.5 2区 农林科学
Molecular Nutrition & Food Research Pub Date : 2025-03-23 DOI: 10.1002/mnfr.70028
Kohei Karasaki, Mari Ishida, Hiroki Kokubo, Chiemi Sakai, Yusuke Kobayashi, Masao Yoshizumi
{"title":"Aged Garlic Extract Attenuates CaCl2-Induced Abdominal Aortic Aneurysm Formation by Inhibiting Matrix Metalloproteinase 9 Expression in Macrophages","authors":"Kohei Karasaki,&nbsp;Mari Ishida,&nbsp;Hiroki Kokubo,&nbsp;Chiemi Sakai,&nbsp;Yusuke Kobayashi,&nbsp;Masao Yoshizumi","doi":"10.1002/mnfr.70028","DOIUrl":"10.1002/mnfr.70028","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Abdominal aortic aneurysm (AAA) is a local enlargement of the abdominal aorta with the risk of its fatal rupture. With lack of established medical treatments reducing the AAA growth, the development of treatment strategies for AAA is warranted. In this study, we examined whether aged garlic extract (AGE), which reportedly has vasoprotective effects, attenuates AAA formation in an animal model. AAAs were induced via CaCl<sub>2</sub> application to the abdominal aortas of C57BL/6J mice. The intake of an AGE-containing diet attenuated the aortic dilatation after AAA induction. Histological analysis showed that the degradation of elastic fibers in AAAs was mild in mice fed AGE compared to that in control mice. In addition, the expression of matrix metalloproteinase 9 (MMP9), a proteolytic enzyme degrading aortic tissue, was decreased in AAAs from mice fed with AGE. In cultured macrophages, AGE significantly inhibited tumor necrosis factor (TNF)-α-induced <i>Mmp9</i> mRNA expression. Furthermore, AGE attenuated TNF-α-induced extracellular signal-regulated kinase (ERK) phosphorylation and <i>c-fos</i> mRNA expression, suggesting the suppressive effect of AGE on ERK-c-Fos-MMP9 axis induced by TNF-α. The present findings indicate that AGE diminishes AAA formation by mitigating tissue destruction, highlighting the potential cardiovascular benefits of AGE intake.</p>\u0000 </section>\u0000 </div>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"69 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143678298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prenatal Intake of High Multivitamins or Folic Acid With or Without Choline Contributes to Gut Microbiota-Associated Dysregulation of Serotonin in Offspring 产前摄入高复合维生素或叶酸(含或不含胆碱)有助于后代肠道微生物群相关的血清素失调
IF 4.5 2区 农林科学
Molecular Nutrition & Food Research Pub Date : 2025-03-23 DOI: 10.1002/mnfr.70044
Jianzhang Dong, Mali Al-Issa, Jenny S. Feeney, Gia V. Shelp, Elizabeth M. Poole, Clara E. Cho
{"title":"Prenatal Intake of High Multivitamins or Folic Acid With or Without Choline Contributes to Gut Microbiota-Associated Dysregulation of Serotonin in Offspring","authors":"Jianzhang Dong,&nbsp;Mali Al-Issa,&nbsp;Jenny S. Feeney,&nbsp;Gia V. Shelp,&nbsp;Elizabeth M. Poole,&nbsp;Clara E. Cho","doi":"10.1002/mnfr.70044","DOIUrl":"10.1002/mnfr.70044","url":null,"abstract":"<p>The gut microbiota is amenable to early nutrition including micronutrients but intake above and below the recommendations commonly occur with unknown consequences. Serotonin (5-hydroxytryptamine [5-HT]) is a monoamine found centrally and peripherally with diverse functions such as food intake regulation via the hypothalamic 5-HT receptor 2C (5-HTR2C). This study determined the impact of prenatal micronutrients on the gut microbiota and serotonergic system in offspring. Pregnant Wistar rats were fed either recommended vitamins (RV), high vitamins (HV), high folic acid with recommended choline (HFRC), or high folic acid with no choline (HFNC). Offspring were fed a high-fat diet for 12 weeks postweaning. HV, HFRC, and HFNC males and females had lower hypothalamic 5-HTR2C protein expression compared to RV. Brain 5-HT concentrations were lower but colon 5-HT concentrations were higher in HV and HFNC males and females and HFRC males compared to RV. Refeeding response after 5-HTR2C agonist was negatively correlated with hypothalamic 5-HTR2C protein expression in males and with brain 5-HT concentrations in females. Random forest revealed top bacterial taxa, which <i>Lactococcus</i>, <i>Ruminococcus</i>, <i>Bacteroides</i>, and <i>Oscillospira</i> showed significant correlations with refeeding response and concentrations of brain and colon 5-HT. In conclusion, excess or imbalanced prenatal consumption of micronutrients leads to gut microbiota-associated disturbances in the serotonergic system in offspring.</p>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"69 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mnfr.70044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677799","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
Arecoline Alleviates T2DM via Gut Microbiota Modulation and Liver Gene Regulation in Mice 槟榔碱通过调节小鼠肠道菌群和肝脏基因调控缓解T2DM
IF 4.5 2区 农林科学
Molecular Nutrition & Food Research Pub Date : 2025-03-23 DOI: 10.1002/mnfr.70015
Meng Xu, Wanggao Li, Yuan Xu, Jiachao Zhang, Hui Xue, Juan Du, Xiaosong Hu
{"title":"Arecoline Alleviates T2DM via Gut Microbiota Modulation and Liver Gene Regulation in Mice","authors":"Meng Xu,&nbsp;Wanggao Li,&nbsp;Yuan Xu,&nbsp;Jiachao Zhang,&nbsp;Hui Xue,&nbsp;Juan Du,&nbsp;Xiaosong Hu","doi":"10.1002/mnfr.70015","DOIUrl":"10.1002/mnfr.70015","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Scope</h3>\u0000 \u0000 <p>Arecoline, the main alkaloid in areca nut, has shown potential in modulating metabolism and gut microbiota. This study aimed to evaluate its therapeutic effects on glucose and lipid metabolism, inflammation, liver function, and potential mechanisms in a Type 2 diabetes mellitus (T2DM) mouse model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>T2DM was established in mice with a high-fat, high-sugar diet, and streptozotocin injections. Arecoline significantly reduced fasting blood glucose, enhanced glucose tolerance, and increased insulin sensitivity. Serum lipid profiles showed marked decreases in total cholesterol, triglycerides, and LDL-C levels. Systemic inflammation, as measured by serum levels of IL-1β, IL-6, and MCP-1, decreased significantly. Improvements in liver function were observed, as indicated by reductions in ALT and AST levels. Liver transcriptomic analysis revealed modulation of pathways related to glutathione metabolism, MAPK signaling, and cAMP signaling, which were involved in insulin signaling and oxidative stress response. Additionally, arecoline mitigated gut dysbiosis by restoring microbial diversity, altering gut microbiota composition, and regulating key pathways involved in NAD biosynthesis and fatty acid β-oxidation, which were critical for maintaining energy homeostasis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Arecoline improves glucose metabolism, lipid profiles, and liver function, while modulating gut microbiota and liver metabolic pathways, showing potential as a therapeutic agent for T2DM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"69 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143678297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Vitamin A-Enriched Diet Increases Urothelial Cell Proliferation by Upregulating Itga3 and Areg After Cyclophosphamide-Induced Injury in Mice 富含维生素a的饮食通过上调Itga3和Areg促进小鼠环磷酰胺损伤后尿路上皮细胞增殖
IF 4.5 2区 农林科学
Molecular Nutrition & Food Research Pub Date : 2025-03-22 DOI: 10.1002/mnfr.70045
Brina Dragar, Simona Kranjc Brezar, Maja Čemažar, Tanja Jesenko, Rok Romih, Mateja Erdani Kreft, Tadeja Kuret, Daša Zupančič
{"title":"Vitamin A-Enriched Diet Increases Urothelial Cell Proliferation by Upregulating Itga3 and Areg After Cyclophosphamide-Induced Injury in Mice","authors":"Brina Dragar,&nbsp;Simona Kranjc Brezar,&nbsp;Maja Čemažar,&nbsp;Tanja Jesenko,&nbsp;Rok Romih,&nbsp;Mateja Erdani Kreft,&nbsp;Tadeja Kuret,&nbsp;Daša Zupančič","doi":"10.1002/mnfr.70045","DOIUrl":"10.1002/mnfr.70045","url":null,"abstract":"<p>Vitamin A (VitA) is an essential nutrient, affecting many cell functions, such as proliferation, apoptosis, and differentiation, all of which are important for the regeneration of various tissues. In this study, we investigated the effects of a VitA-enriched diet on the regeneration of the urothelium of the urinary bladder in mice after cyclophosphamide (CP)-induced injury. Female mice were fed VitA-enriched and normal diet for 1 week before receiving an intraperitoneal injection of CP (150 mg/kg). Urinary bladders were removed 1 and 3 days after CP. On Day 1, RNA sequencing showed that VitA upregulated two Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways: the cell cycle and the PI3K-Akt pathway. This was confirmed by qPCR, which showed significantly increased expression of the <i>Itga3</i> and <i>Areg</i> genes. In addition, the effect of VitA on the proliferation of urothelial cells was analyzed by immunohistochemistry of Ki-67, which confirmed an increased proliferation rate. No significant effects of the VitA-enriched diet were observed on the expression of apoptosis-related genes and on differentiation-related markers of superficial urothelial cells. Our results suggest that a VitA-enriched diet improves early urothelial regeneration after CP-induced injury by promoting cell proliferation.</p>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"69 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mnfr.70045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672764","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
Trends in Coenzyme Q10 Supplement Use and Associations With All-Cause and Cardiovascular Mortality: A Population-Based Cohort Study 辅酶 Q10 补充剂的使用趋势及其与全因死亡率和心血管死亡率的关系:基于人群的队列研究
IF 4.5 2区 农林科学
Molecular Nutrition & Food Research Pub Date : 2025-03-21 DOI: 10.1002/mnfr.70019
Lihan Liang, Zepei Zhong, Zezhong Tian, Zhihao Liu, Huiying Kuang, Fang He, Ruijie Wang, Shanshan Hou, Yan Yang
{"title":"Trends in Coenzyme Q10 Supplement Use and Associations With All-Cause and Cardiovascular Mortality: A Population-Based Cohort Study","authors":"Lihan Liang,&nbsp;Zepei Zhong,&nbsp;Zezhong Tian,&nbsp;Zhihao Liu,&nbsp;Huiying Kuang,&nbsp;Fang He,&nbsp;Ruijie Wang,&nbsp;Shanshan Hou,&nbsp;Yan Yang","doi":"10.1002/mnfr.70019","DOIUrl":"10.1002/mnfr.70019","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Coenzyme Q10 (CoQ10) is a fat-soluble nutrient, which has antioxidant and anti-inflammatory properties. However, there is insufficient evidence on its daily use and the association with mortality. We aimed to evaluate the trends of CoQ10 supplement use among US noninstitutionalized adults and explore its associations with all-cause and CVD mortality. A prospective cohort study used data from the National Health and Nutrition Examination Survey (1999–2018). The association of CoQ10 supplementation with mortality was assessed with Cox proportional hazard models. The overall reported prevalence of CoQ10 supplement use increased from 1.2% (95% CI 0.7%–1.8%) in 1999–2000 to 4.6% (95% CI 3.4%–6.1%) in 2017–2018 (linear <i>p</i>  =  0.002). During an average of 9.8 years of follow-up, 5237 deaths were identified, including 1428 deaths due to CVD. In the multivariable model, CoQ10 supplement use was not associated with all-cause mortality (HR 1.00, 95% CI 0.77–1.30, <i>p</i> = 0.996) and CVD mortality (HR 1.30, 95% CI 0.89–1.90, <i>p</i> = 0.170). Subgroup analyses suggested that the use of CoQ10 supplements was associated with a higher all-cause mortality in obese participants (HR 1.45, 95% CI 1.01–2.08, <i>p</i> for interaction = 0.013). Although the prevalence of CoQ10 supplement use experienced continuous growth from 1999 to 2018 in the general adults of NHANES, CoQ10 supplementation was not associated with all-cause and CVD mortality.</p>\u0000 </section>\u0000 </div>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"69 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143666481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Protocatechuic Acid Reduces Liver Fatty Acid Uptake in HFD-Fed Mice Associated With the Inhibition of DHHC5-Mediated CD36 Palmitoylation 原儿茶酸通过抑制dhhc5介导的CD36棕榈酰化来减少hfd喂养小鼠肝脏脂肪酸摄取
IF 5.2 2区 农林科学
Molecular Nutrition & Food Research Pub Date : 2025-03-20 DOI: 10.1002/mnfr.70012
Jia Li, Peiran Li, Xue Wu, Zibin Li, Yunlong Li, Chao Liu, Ji Bian, Lin Han, Min Wang
{"title":"Protocatechuic Acid Reduces Liver Fatty Acid Uptake in HFD-Fed Mice Associated With the Inhibition of DHHC5-Mediated CD36 Palmitoylation","authors":"Jia Li, Peiran Li, Xue Wu, Zibin Li, Yunlong Li, Chao Liu, Ji Bian, Lin Han, Min Wang","doi":"10.1002/mnfr.70012","DOIUrl":"https://doi.org/10.1002/mnfr.70012","url":null,"abstract":"Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent and has emerged as a pressing issue for human health. A highly palmitoylated cluster of differentiation 36 (CD36) promotes free fatty acid (FFA) uptake, which contributes to the development of MASLD. Protocatechuic acid (PCA), the main metabolite of anthocyanins, was reported to inhibit MASLD by regulating the expression of CD36. However, the impact of PCA on CD36 palmitoylation has not been extensively studied. In the present study, we found that PCA could significantly reduce lipid uptake and accumulation in hepatocytes by decreasing CD36 palmitoylation. Inhibitors were used to prove that PCA suppressed CD36 palmitoylation by lowering zinc finger DHHC-type palmitoyltransferase 5 (DHHC5) palmitoylation, but not in an acyl protein thioesterase 1 (APT1)-dependent manner. Further experiments showed that PCA-mediated inhibition of DHHC5 palmitoylation and acyltransferase activity was closely related to the reduction of the CD36/Fyn/Lyn complex. PCA diminished the palmitoylation of CD36 and DHHC5 and ultimately lessened lipid uptake and accumulation in hepatocytes.","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"124 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Issue Information: Mol. Nutr. Food Res. 6'25 发布信息:Mol. Nutr。Food Res. 6'25
IF 4.5 2区 农林科学
Molecular Nutrition & Food Research Pub Date : 2025-03-20 DOI: 10.1002/mnfr.70032
{"title":"Issue Information: Mol. Nutr. Food Res. 6'25","authors":"","doi":"10.1002/mnfr.70032","DOIUrl":"10.1002/mnfr.70032","url":null,"abstract":"","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"69 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mnfr.70032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660648","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
Enhancing Colorectal Cancer Treatment: The Role of Bifidobacterium in Modulating Gut Immunity and Mitigating Capecitabine-Induced Toxicity 加强结直肠癌治疗:双歧杆菌在调节肠道免疫和减轻卡培他滨诱导的毒性中的作用
IF 4.5 2区 农林科学
Molecular Nutrition & Food Research Pub Date : 2025-03-20 DOI: 10.1002/mnfr.70023
Aswathi Ramesh, Dhasarathdev Srinivasan, Rajasekaran Subbarayan, Ankush Chauhan, Loganathan Krishnamoorthy, Jeevan Kumar, Madhan Krishnan, Rupendra Shrestha
{"title":"Enhancing Colorectal Cancer Treatment: The Role of Bifidobacterium in Modulating Gut Immunity and Mitigating Capecitabine-Induced Toxicity","authors":"Aswathi Ramesh,&nbsp;Dhasarathdev Srinivasan,&nbsp;Rajasekaran Subbarayan,&nbsp;Ankush Chauhan,&nbsp;Loganathan Krishnamoorthy,&nbsp;Jeevan Kumar,&nbsp;Madhan Krishnan,&nbsp;Rupendra Shrestha","doi":"10.1002/mnfr.70023","DOIUrl":"10.1002/mnfr.70023","url":null,"abstract":"<div>\u0000 \u0000 <p>Colorectal cancer (CRC) is the third leading cause of cancer-related mortality globally and presents significant challenges in treatment and patient care. Capecitabine, a widely used prodrug of 5-fluorouracil (5-FU), offers targeted delivery with reduced systemic toxicity compared to traditional chemotherapies. However, capacitabine is associated with adverse effects, such as hand-foot syndrome, gastrointestinal issues, and mucositis. Emerging evidence suggests that probiotics, particularly Bifidobacterium, play a pivotal role in gut microbiota modulation, promoting anti-inflammatory cytokines and short-chain fatty acids, such as butyrate, which possess both intestinal protective and anti-cancer properties. In this review, we explored the potential of Bifidobacterium to improve chemotherapy outcomes by mitigating inflammation and enhancing mucosal immunity in CRC patients. Furthermore, we demonstrated in silico approaches, including molecular docking and protein–protein interaction analysis, for Bifidobacterium and Toll-like receptor 2 (TLR-2), a key mediator of intestinal immunity. Docking results revealed strong binding affinity, suggesting the activation of anti-inflammatory pathways. Notably, this interaction enhanced IL-10 production while reducing pro-inflammatory cytokines, such as IL-6 and TNF-α, fostering gut homeostasis and mitigating chronic inflammation, a key driver of CRC progression. Therefore, future research should focus on personalized probiotics and validating their synergy with chemotherapy and immunotherapy to improve CRC treatment outcomes.</p>\u0000 </div>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"69 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Improvement of Glucose Metabolism by Pennogenin 3-O-β-Chacotrioside via Activation of IRS/PI3K/Akt Signaling and Mitochondrial Respiration in Insulin-Resistant Hepatocytes Pennogenin 3-O-β-Chacotrioside通过激活IRS/PI3K/Akt信号和线粒体呼吸改善胰岛素抵抗肝细胞的葡萄糖代谢
IF 4.5 2区 农林科学
Molecular Nutrition & Food Research Pub Date : 2025-03-19 DOI: 10.1002/mnfr.70010
Jae-In Lee, Hee Min Lee, Jae-Ho Park, Yu Geon Lee
{"title":"Improvement of Glucose Metabolism by Pennogenin 3-O-β-Chacotrioside via Activation of IRS/PI3K/Akt Signaling and Mitochondrial Respiration in Insulin-Resistant Hepatocytes","authors":"Jae-In Lee,&nbsp;Hee Min Lee,&nbsp;Jae-Ho Park,&nbsp;Yu Geon Lee","doi":"10.1002/mnfr.70010","DOIUrl":"10.1002/mnfr.70010","url":null,"abstract":"<div>\u0000 \u0000 <p>Scope: Insulin resistance (IR), which causes chronic hyperglycemia, has been one of the most prevalent components of metabolic syndrome over the centuries. Pennogenin 3-<i>O</i>-β-chacotrioside (P3C), the main steroid glycoside derived from <i>Paris polyphylla</i>, has been found to exert various biological activities. However, the exact role of P3C on glucose metabolism in the IR state remains unexplored. Methods and results: To induce IR, AML12 cells were exposed to glucose (27 mM) and insulin (10 µg/mL) and then incubated with P3C (0.25 or 0.5 µM) for 24 h. The effects of P3C on glucose metabolism in insulin-resistant AML12 cells were evaluated through glucose consumption assays, real-time quantitative polymerase chain reaction (qPCR), Western blotting, and metabolic analysis for extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Our data showed that P3C significantly improved insulin sensitivity in AML12 hepatocytes with high glucose-induced IR. P3C stimulated insulin sensitivity and glucose uptake by activating the IRS/PI3K/Akt signaling pathway, which enhances glycogen synthesis and suppresses gluconeogenesis in insulin-resistant AML12 cells. In addition, P3C treatment increased the protein expression of p-AMPK and PGC1α, as well as the expression of oxidative phosphorylation complex proteins, potentially enhancing mitochondrial oxidative respiration. Conclusions: Our findings imply that P3C could be a therapeutic option for improving metabolic abnormalities associated with IR.</p>\u0000 </div>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"69 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mucus Barrier Weakens the Inhibitory Activity of Pyrogallol-Based Polyphenols Against α-Glucosidase 粘液屏障减弱邻苯三酚类多酚对α-葡萄糖苷酶的抑制活性
IF 4.5 2区 农林科学
Molecular Nutrition & Food Research Pub Date : 2025-03-19 DOI: 10.1002/mnfr.202400838
Yi Wang, Suqing Lan, Laiming Zhang, Yunxuan Li, Ziyang Deng, Xingqian Ye, Haibo Pan, Shiguo Chen
{"title":"Mucus Barrier Weakens the Inhibitory Activity of Pyrogallol-Based Polyphenols Against α-Glucosidase","authors":"Yi Wang,&nbsp;Suqing Lan,&nbsp;Laiming Zhang,&nbsp;Yunxuan Li,&nbsp;Ziyang Deng,&nbsp;Xingqian Ye,&nbsp;Haibo Pan,&nbsp;Shiguo Chen","doi":"10.1002/mnfr.202400838","DOIUrl":"10.1002/mnfr.202400838","url":null,"abstract":"<div>\u0000 \u0000 <p>Scope: Polyphenols reportedly possess strong in vitro α-glucosidase inhibitory activity, even higher than acarbose, but their in vivo regulation on postprandial hyperglycemia is poor. So far this typical problem of polyphenols remains unsolved, greatly hindering their application as α-glucosidase inhibitors. Methods and results: Here, we identify the small intestinal mucus layer acts as a barrier to significantly reduce in vivo α-glucosidase inhibitory activity of epigallocatechin gallate, prodelphinidin B digallate (proDB DG), and proanthocyanidins from Chinese bayberry leaves. Multispectroscopy, rheology, solvent method, and molecular docking analysis showed that these pyrogallol-based polyphenols, especially proDB DG strongly interacted with small intestinal mucins through hydrogen bonding, hydrophobic interactions, and electrostatic interactions. These interactions block polyphenols from penetrating the mucus layer, resulting in their low binding rates with α-glucosidase in vivo. Besides, polyphenol-driven aggregation of the mucins enhanced the barrier function and reduced the permeability of the mucus layer, resulting in delayed digestion and absorption of carbohydrates. Conclusions: The mucus barrier weakens the inhibitory activity of pyrogallol-based polyphenols against α-glucosidase. Hence, overcoming the mucus barrier is a promising strategy to improve the regulation of pyrogallol-based polyphenols against postprandial hyperglycemia in vivo, which helps them to become novel α-glucosidase inhibitors in the clinic.</p>\u0000 </div>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"69 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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