{"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, Hee Min Lee, Jae-Ho Park, Yu Geon Lee","doi":"10.1002/mnfr.70010","DOIUrl":"https://doi.org/10.1002/mnfr.70010","url":null,"abstract":"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.","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"14 5 1","pages":""},"PeriodicalIF":5.2,"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}
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, Suqing Lan, Laiming Zhang, Yunxuan Li, Ziyang Deng, Xingqian Ye, Haibo Pan, Shiguo Chen","doi":"10.1002/mnfr.202400838","DOIUrl":"https://doi.org/10.1002/mnfr.202400838","url":null,"abstract":"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.","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"91 1","pages":""},"PeriodicalIF":5.2,"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}
Pengfei Li, Yong Zhang, Hedong Lang, Pengfei Hou, Yu Yao, Ruiliang Zhang, Xiaolan Wang, Qianyong Zhang, Mantian Mi, Long Yi
{"title":"Dihydromyricetin Promotes Glucagon-Like Peptide-1 Secretion and Improves Insulin Resistance by Modulation of the Gut Microbiota-CDCA Pathway","authors":"Pengfei Li, Yong Zhang, Hedong Lang, Pengfei Hou, Yu Yao, Ruiliang Zhang, Xiaolan Wang, Qianyong Zhang, Mantian Mi, Long Yi","doi":"10.1002/mnfr.202400491","DOIUrl":"https://doi.org/10.1002/mnfr.202400491","url":null,"abstract":"Insulin resistance is a common metabolic disease, and its pathogenesis is still unclear. The decrease of glucagon-like peptide-1 (GLP-1) level mediated by the alteration of gut microbiota may be the pathogenesis. The study was to investigate the regulatory effect of dihydromyricetin (DHM) on GLP-1 level and insulin resistance induced by high-fat diet (HFD), and to further explore its possible molecular mechanism. Mice were fed an HFD to establish the model of insulin resistance to determine whether DHM had a protective effect. DHM could improve insulin resistance. DHM increased serum GLP-1 by improving intestinal GLP-1 secretion and inhibiting GLP-1 decomposition, associated with the alteration of intestinal intraepithelial lymphocytes (IELs) proportions and decreased expression of CD26 in IELs and TCRαβ<sup>+</sup> CD8αβ<sup>+</sup> IELs in HFD-induced mice. DHM could ameliorate GLP-1 level and insulin resistance by modulation of gut microbiota and the metabolites, particularly the regulation of chenodeoxycholic acid (CDCA) content, followed by the inhibition of farnesoid X receptor (FXR) expression in intestinal L cells and increased glucagon gene (Gcg) mRNA expression and GLP-1 secretion. This research demonstrates the role of “gut microbiota-CDCA” pathway in the improvement of intestinal GLP-1 levels in HFD-induced mice by DHM administration, providing a new target for the prevention of insulin resistance.","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"87 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143608712","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}
Michael Leonidas Chikindas, Donald W. Schaffner, Svetoslav Dimitrov Todorov
{"title":"New Food Ingredients: The Challenge of Potential New Pathogens and Spoilage Issues","authors":"Michael Leonidas Chikindas, Donald W. Schaffner, Svetoslav Dimitrov Todorov","doi":"10.1002/mnfr.70022","DOIUrl":"https://doi.org/10.1002/mnfr.70022","url":null,"abstract":"The UN Sustainable Development Goal 2 (Zero Hunger) highlights the need to produce sufficient food commodities to meet the world's population demands and combat hunger, while also respecting the environment and adhering to sustainability principles. Since the beginning of the 21st century, new ideas, ingredients, and technologies have emerged that could significantly transform the food industry. These transformations may alter the rules of food production by integrating traditional knowledge with new technologies and scientific advancements. These innovative processes align to feed the world's growing population through sustainable production. The introduction of new ingredients in food products may necessitate new food safety and/or quality requirements. Using several examples of both traditional and new ingredients such as insects, plants, marine plants, mycoproteins, meat crops, cellulose, and chitin (as representative examples), we illustrate the need to determine which microorganisms to look for when it comes to the microbiological quality and safety of such food products. This opinion does not seek to establish new microbiological guidelines or standards for safety and quality. Instead, our goal is to emphasize the need for a process to define new microbiological criteria, ensuring the quality and safety of emerging food products.","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"54 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143608710","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}
Larissa de Mattos Manhães, Ludmilla Santana, Marcelo Ribeiro Alves, Priscila Mansur Leal, Patricia Coelho de Velasco, Isabelle Santana, Jessyca Sousa de Brito, Denise Mafra, Natália Alvarenga Borges
{"title":"Trimethylamine N-Oxide Plasma Levels Following Red Meat and Cod Fish Intake: A Pilot Crossover Trial in Hemodialysis Patients","authors":"Larissa de Mattos Manhães, Ludmilla Santana, Marcelo Ribeiro Alves, Priscila Mansur Leal, Patricia Coelho de Velasco, Isabelle Santana, Jessyca Sousa de Brito, Denise Mafra, Natália Alvarenga Borges","doi":"10.1002/mnfr.70031","DOIUrl":"https://doi.org/10.1002/mnfr.70031","url":null,"abstract":"Scope: The uremic toxin trimethylamine <i>N</i>-oxide (TMAO) accumulates in patients with chronic kidney disease (CKD) and is associated with its progression, cardiovascular disease, and other complications. The gut microbiota produces TMAO from substrates mainly found in red meat, eggs, and dairy. However, some saltwater fish also contain high levels of TMAO. Although fish consumption is generally linked to beneficial effects, its effects on CKD patients require further research. Methods and results: This study compares the effect of red meat and cod fish intake on TMAO plasma levels in CKD patients undergoing hemodialysis (HD). Participants received a single animal protein source (red meat vs. cod fish) for lunch and dinner for four consecutive days (each intervention), with a 2-week washout period in between. TMAO plasma levels were analyzed using LC-MS/MS. All 14 patients concluded the red meat intervention, while one refused to participate in the fish intervention. No significant difference in TMAO plasma levels was found post-red meat (<i>p</i> = 0.21) or fish intervention (<i>p</i> = 0.91), as well as between groups (<i>p</i> = 0.43). Conclusion: In this study, 4 days of red meat and cod fish intake did not significantly impact TMAO levels in HD patients, while other factors may be associated with their circulating levels.","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"68 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143608711","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}
Gemma Beasy, Federico Bernuzzi, Priscilla Day-Walsh, Perla Tronsco-Rey, Marianne Defernez, Shikha Saha, Richard F. Mithen, Maria H. Traka, Paul A. Kroon
{"title":"S-Methyl Methanethiosulfonate, the Main Human Metabolite of S-Methyl-L-Cysteine Sulfoxide, Alters Energy Metabolism in Prostate Cancer Cells","authors":"Gemma Beasy, Federico Bernuzzi, Priscilla Day-Walsh, Perla Tronsco-Rey, Marianne Defernez, Shikha Saha, Richard F. Mithen, Maria H. Traka, Paul A. Kroon","doi":"10.1002/mnfr.70008","DOIUrl":"https://doi.org/10.1002/mnfr.70008","url":null,"abstract":"Cruciferous and allium vegetables contain the sulfur compound S-methyl-L-cysteine-sulfoxide (SMCSO). Considering SMCSO is found at a higher abundance compared to the glucosinolates, there are limited reports on its effect on health, with the majority of the evidence on the beneficial effects on glucose metabolism in rodent models. In the current study, we investigated the metabolic effects of SMCSO and its metabolite, S-methyl methanethiosulfonate (MMTSO), on prostate cancer metabolism. DU145 prostate cancer cells were cultured in 5.5 mM (basal), 10 mM (intermediate) and 25 mM (high) glucose concentrations in the presence of SMCSO or MMTSO (100 µM). Using Seahorse technology, MMTSO but not SMCSO reduced mitochondrial metabolism, mitochondrial ATP, and the percentage of oxidative phosphorylation and increased the fatty acid dependency of DU145 cells. Transcriptomic and metabolomic analyses observed cellular and energy metabolism pathways and immune response changes.","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"91 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582447","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}
{"title":"Anti-Osteoporosis and Bone Protective Effects of Resveratrol in Rats With Chronic Kidney Disease-Induced Osteoporosis","authors":"Enzhe Zhao, Jian Zhu, Haihu Hao, Rui Zhang, Dou Wu","doi":"10.1002/mnfr.70017","DOIUrl":"https://doi.org/10.1002/mnfr.70017","url":null,"abstract":"Chronic kidney disease (CKD)–induced osteoporosis is a new concept that implies CKD-related impaired bone quality. Resveratrol (RES) is a natural component, known for its anti-inflammatory and anti-osteoporotic effects. In the present study, we aimed to investigate the bone-protective and anti-osteoporotic effects of resveratrol in rats with chronic kidney disease-induced osteoporosis. The 5/6th nephrectomy (Nx) model of CKD was established. Resveratrol and alendronate (ALN), as standard drug, were administered for 45 days. Blood samples and femurs were collected and subjected to molecular analysis, micro-CT, and bone mechanical tests. The results showed a significant decrease in Ca levels but no significant changes in 1,25 vitamin D and phosphorus levels in untreated and treated CKD groups. Treatment with RES and ALN did not reverse the increase of serum parathyroid hormone while reducing the elevated FGF-23 levels. Unlike ALN, RES had no significant effect on increased alkaline phosphatas levels or decreased osteocalcin and OPG levels in CKD rats. Moreover, results showed that RES reversed the increase of RANKL and TRAP in serum and femur tissue close to the control level, leading to an improvement in bone strength and microarchitecture. In conclusion, the present study showed beneficial anti-osteoporotic effects of RES on CKD-induced osteoporosis.","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"14 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143561224","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}
{"title":"Postbiotics Made From Selected Lactic Acid Bacteria Improves Chronic Restraint Stress-Induced Anhedonia and Sleep Disorders","authors":"Jinxing Li, Yimei Wang, Simou Wu, Zhimo Zhou, Wen Jia, Xi Shen, Yun Li, Fang He, Ruyue Cheng","doi":"10.1002/mnfr.70005","DOIUrl":"https://doi.org/10.1002/mnfr.70005","url":null,"abstract":"Sleep disorders have become one of the most prevalent neuropsychiatric disorders in recent years. This study aimed to investigate the effects of postbiotics derived from selected lactic acid bacteria on anhedonia and sleep disorders in chronic restraint stress (CRS)-induced mice, as well as their potential mechanisms. Mice were orally administered normal saline, low, medium, or high doses of postbiotics for 30 days, with CRS applied from days 1 to 21. The medium dose of postbiotics significantly increased the sucrose preference index, and the high dose of postbiotics significantly increased sleep duration. Postbiotic treatment effectively restored the diversity and composition of the gut microbiota to levels comparable to those observed in the vehicle (Veh) group. Furthermore, low and medium doses of postbiotics significantly reduced serum corticosterone levels, and medium and high doses significantly reduced serum IL-1β levels. Additionally, postbiotics administration significantly increased glutamate and GABA levels in both the prefrontal cortex and hypothalamus, as well as GABA levels in the feces. These results indicate that postbiotics alleviate CRS-induced anhedonia and sleep disorders in a dose-dependent manner. This effect may be mediated through the restoration of homeostasis in the MGB axis, HPA axis, inflammation pathways, and neurotransmitter balance.","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"53 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143561223","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}