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1.
Food Res Int ; 188: 114451, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38823860

ABSTRACT

Excessive intake of sugar has become a public concern. However, it is challenging for food industries to decrease sugar level without sacrificing safety and sensory profile. Odor-induced sweetness enhancement (OISE) is believed to be a novel and promising strategy for sugar reduction. In order to investigate the OISE effect of mango aroma and evaluate its degree of sugar reduction in low-sugar beverages, a mathematical model was constructed through sensory evaluation in this study. The results showed that the maximum liking of low-sugar model beverages was 4.28 % sucrose and 0.57 % mango flavor. The most synergistic of OISE was at the concentration level of 2.24 % sucrose + 0.25 % mango flavor, which was equivalent to 2.96 % pure sucrose solution. With 32.14 % sugar reduction, the mango aroma was suggested to generate the OISE effect. However, the same level of garlic aroma was not able to enhance sweetness perception, suggesting that the congruency of aroma and taste is a prerequisite for the OISE effect to occur. This study demonstrated that the cross-modal interaction of mango aroma on sweetness enhancement in low-sugar model beverages could provide practical guidance for developing sugar-reduced beverages without applying sweeteners.


Subject(s)
Mangifera , Odorants , Taste , Humans , Odorants/analysis , Mangifera/chemistry , Female , Adult , Male , Young Adult , Sweetening Agents/analysis , Smell , Sucrose/analysis , Consumer Behavior , Beverages/analysis , Taste Perception , Flavoring Agents/analysis
2.
Curr Opin Clin Nutr Metab Care ; 27(4): 344-349, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38836812

ABSTRACT

PURPOSE OF REVIEW: Recommendations on the use of nonsugar sweeteners are contradictory, even if they come from official sources. The aim is to review and discuss recent findings on the potential impact of nonsugar sweeteners on human health. RECENT FINDINGS: While randomized controlled trials (RCTs) with short duration and risk factors endpoints mostly show favourable effects on body weight and cardiometabolic parameters when nonsugar sweeteners are used to replaced sugar-sweetened products, observational studies mostly show a positive association between the consumption of nonsugar sweeteners and cardiometabolic diseases. The conflicting results may be explained by the heterogenous nature of nonsugar sweeteners but also likely is a consequence of serious weaknesses of available studies. SUMMARY: For more evidence-based recommendations for practice and policy, scientifically sound studies with long follow-up are required.


Subject(s)
Observational Studies as Topic , Randomized Controlled Trials as Topic , Humans , Sweetening Agents , Non-Nutritive Sweeteners , Cardiovascular Diseases/prevention & control , Risk Factors , Risk Assessment , Body Weight/drug effects
3.
BMC Res Notes ; 17(1): 155, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38840123

ABSTRACT

BACKGROUND AND OBJECTIVE: Aspartame (L-aspartyl L-phenylalanine methyl ester) is an artificial sweetener widely used as a sugar substitute. There are concerns regarding the effects of high aspartame doses on the kidney owing to oxidative stress; however, whether the maximum allowed dose of aspartame in humans affects the kidneys remains unknown. Therefore, in this study, we investigated whether the maximum allowed dose of aspartame in humans affects the kidneys. METHODS: In this study, animals were fed a folate-deficient diet to mimic human aspartame metabolism. Eight-week-old ICR mice were divided into control (CTL), 40 mg/kg/day of aspartame-administered (ASP), folate-deficient diet (FD), and 40 mg/kg/day of aspartame-administered with a folate-deficient diet (FD + ASP) groups. Aspartame was administered orally for eight weeks. Thereafter, we evaluated aspartame's effect on kidneys via histological analysis. RESULTS: There were no differences in serum creatinine and blood urea nitrogen levels between the CTL and ASP groups or between the FD and FD + ASP groups. There was no histological change in the kidneys in any group. The expression of superoxide dismutase and 4-hydroxy-2-nonenal in the kidney did not differ between the CTL and ASP groups or the FD and FD + ASP groups. CONCLUSION: Our findings indicate that the allowed doses of aspartame in humans may not affect kidney function or oxidative states.


Subject(s)
Aspartame , Kidney , Mice, Inbred ICR , Oxidative Stress , Sweetening Agents , Animals , Aspartame/pharmacology , Kidney/drug effects , Kidney/metabolism , Sweetening Agents/pharmacology , Sweetening Agents/administration & dosage , Mice , Male , Oxidative Stress/drug effects , Antioxidants/pharmacology , Antioxidants/metabolism , Superoxide Dismutase/metabolism , Blood Urea Nitrogen
4.
Food Res Int ; 183: 114185, 2024 May.
Article in English | MEDLINE | ID: mdl-38760122

ABSTRACT

Low- and no-calorie sweeteners reduce the amount of carbohydrates in foods and beverages. However, concerns about taste perception surrounding the role of non-nutritive sweeteners in the oral cavity remain unanswered. One of the parameters that influences taste perception is the diffusion coefficient of the sweetener molecules inside the mucin layer lining the mouth. This study investigated the impact of diffusion coefficients of common high-intensity sweeteners on taste perception focusing on the sweeteners' diffusion through mucin. Transwell Permeable Support well plates were used to measure diffusion coefficients of samples that were collected at specific intervals to estimate the coefficients based on concentration measurements. The diffusion coefficients of acesulfame-K, aspartame, rebaudioside M, sucralose, and sucrose with and without NaCl were compared. We found that different sweeteners show different diffusion behavior through mucin and that the presence of salt enhances the diffusion. These findings contribute insights into the diffusion of high-intensity sweeteners, offer a way to evaluate diffusion coefficients in real-time, and inform the development of products with improved taste profiles.


Subject(s)
Mucins , Sucrose , Sweetening Agents , Diffusion , Mucins/metabolism , Sucrose/analogs & derivatives , Taste Perception , Humans , Thiazines
5.
Int J Mol Sci ; 25(10)2024 May 16.
Article in English | MEDLINE | ID: mdl-38791474

ABSTRACT

Sweetness in food delivers a delightful sensory experience, underscoring the crucial role of sweeteners in the food industry. However, the widespread use of sweeteners has sparked health concerns. This underscores the importance of developing and screening natural, health-conscious sweeteners. Our study represents a groundbreaking venture into the discovery of such sweeteners derived from egg and soy proteins. Employing virtual hydrolysis as a novel technique, our research entailed a comprehensive screening process that evaluated biological activity, solubility, and toxicity of the derived compounds. We harnessed cutting-edge machine learning methodologies, specifically the latest graph neural network models, for predicting the sweetness of molecules. Subsequent refinements were made through molecular docking screenings and molecular dynamics simulations. This meticulous research approach culminated in the identification of three promising sweet peptides: DCY(Asp-Cys-Tyr), GGR(Gly-Gly-Arg), and IGR(Ile-Gly-Arg). Their binding affinity with T1R2/T1R3 was lower than -15 kcal/mol. Using an electronic tongue, we verified the taste profiles of these peptides, with IGR emerging as the most favorable in terms of taste with a sweetness value of 19.29 and bitterness value of 1.71. This study not only reveals the potential of these natural peptides as healthier alternatives to traditional sweeteners in food applications but also demonstrates the successful synergy of computational predictions and experimental validations in the realm of flavor science.


Subject(s)
Egg Proteins , Molecular Docking Simulation , Peptides , Soybean Proteins , Sweetening Agents , Taste , Soybean Proteins/chemistry , Sweetening Agents/chemistry , Egg Proteins/chemistry , Egg Proteins/metabolism , Peptides/chemistry , Molecular Dynamics Simulation , Humans , Receptors, G-Protein-Coupled/metabolism , Receptors, G-Protein-Coupled/chemistry
6.
Pharmacol Res ; 204: 107211, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38744400

ABSTRACT

Several non-caloric sweeteners exhibit a delay in sweetness onset and a sweetness linger after sampling. These temporal properties are thought to be the result of non-specific interactions with cell membranes and proteins in the oral cavity. Data and analysis presented in this report also support the potential involvement of receptor affinity and binding kinetics to this phenomenon. In general, affected sweeteners exhibit distinctly higher binding affinity compared to carbohydrate sweeteners, which do not have temporal issues. In addition, binding kinetic simulations illustrate much slower receptor binding association and dissociation kinetics for a set of non-caloric sweeteners presenting temporal issues, in comparison to carbohydrate sweeteners. So, the higher affinity of some non-caloric sweeteners, dictating lower use levels, and affecting binding kinetics, could contribute to their delay and linger in sweetness perception. Simple pharmacology principles could explain, at least in part, some of the temporal issues of sweeteners.


Subject(s)
Sweetening Agents , Humans , Sweetening Agents/pharmacology , Taste/drug effects , Animals , Kinetics , Receptors, G-Protein-Coupled/metabolism , Taste Perception/drug effects
7.
Sci Rep ; 14(1): 11492, 2024 05 20.
Article in English | MEDLINE | ID: mdl-38769413

ABSTRACT

The research employed network toxicology and molecular docking techniques to systematically examine the potential carcinogenic effects and mechanisms of aspartame (L-α-aspartyl-L-phenylalanine methyl ester). Aspartame, a commonly used synthetic sweetener, is widely applied in foods and beverages globally. In recent years, its safety issues, particularly the potential carcinogenic risk, have garnered widespread attention. The study first constructed an interaction network map of aspartame with gastric cancer targets using network toxicology methods and identified key targets and pathways. Preliminary validation was conducted through microarray data analysis and survival analysis, and molecular docking techniques were employed to further examine the binding affinity and modes of action of aspartame with key proteins. The findings suggest that aspartame has the potential to impact various cancer-related proteins, potentially raising the likelihood of cellular carcinogenesis by interfering with biomolecular function. Furthermore, the study found that the action patterns and pathways of aspartame-related targets are like the mechanisms of known carcinogenic pathways, further supporting the scientific hypothesis of its potential carcinogenicity. However, given the complexity of the in vivo environment, we also emphasize the necessity of validating these molecular-level findings in actual biological systems. The study introduces a fresh scientific method for evaluating the safety of food enhancers and provides a theoretical foundation for shaping public health regulations.


Subject(s)
Aspartame , Carcinogens , Molecular Docking Simulation , Aspartame/chemistry , Aspartame/adverse effects , Aspartame/metabolism , Aspartame/toxicity , Humans , Carcinogens/toxicity , Carcinogens/chemistry , Sweetening Agents/chemistry , Sweetening Agents/adverse effects , Sweetening Agents/toxicity , Stomach Neoplasms/chemically induced
8.
Food Chem ; 453: 139622, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-38761729

ABSTRACT

For health and safety reasons, the search for green, healthy, and low-calorie sweeteners with good taste has become the demand of many consumers. Furthermore, the need for sugar substitutes of natural origin has increased dramatically. In this review, we briefly discussed the safety and health benefits of stevia sweeteners and enumerated some examples of physiological functions of steviol glycosides (SGs), such as anti-inflammatory, anti-obesity, antihypertensive, anti-diabetes, and anticaries, citing various evidence related to their application in the food industry. The latest advances in emerging technologies for extracting and purifying SGs and the process variables and operational strategies were discussed. The impact of the extraction methods and their comparison against the conventional techniques have also been demonstrated. These technologies use minimal energy solvents and simplify subsequent purification stages, making viable alternatives suitable for a possible industrial application. Furthermore, we also elucidated the potential for advancing and applying the natural sweeteners SGs.


Subject(s)
Diterpenes, Kaurane , Plant Extracts , Stevia , Sweetening Agents , Stevia/chemistry , Diterpenes, Kaurane/isolation & purification , Diterpenes, Kaurane/chemistry , Sweetening Agents/isolation & purification , Sweetening Agents/chemistry , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Humans , Glucosides/isolation & purification , Glucosides/chemistry , Animals , Glycosides/isolation & purification , Glycosides/chemistry
9.
Food Chem ; 453: 139654, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-38781899

ABSTRACT

As a natural low-calorie sweetener, Mogroside V (Mog-V) has gradually become one of the alternatives to sucrose with superior health attributes. However, Mog-V will bring unpleasant aftertastes when exceeding a threshold concentration. To investigate the possibility of soy protein isolates (SPIs), namely ß-conglycinin (7S), and glycinin (11S) as flavor-improving agents of Mog-V, the binding mechanism between Mog-V and SPIs was explored through multi-spectroscopy, particle size, zeta potential, and computational simulation. The results of the multi-spectroscopic experiments indicated that Mog-V enhanced the fluorescence of 7S/11S protein in a static mode. The binding affinity of 7S-Mog-V was greater compared with 11S-Mog-V. Particle size and zeta potential analysis revealed that the interaction could promote aggregation of 7S/11S protein with different stability. Furthermore, computational simulations further confirmed that Mog-V could interact with the 7S/11S protein in different ways. This research provides a theoretical foundation for the development and application of SPI to improve the flavor of Mog-V, opening a new avenue for further expanding the market demand for Mog-V.


Subject(s)
Soybean Proteins , Sweetening Agents , Soybean Proteins/chemistry , Soybean Proteins/metabolism , Sweetening Agents/chemistry , Sweetening Agents/metabolism , Globulins/chemistry , Globulins/metabolism , Protein Binding , Antigens, Plant/chemistry , Antigens, Plant/metabolism , Computer Simulation , Seed Storage Proteins/chemistry , Seed Storage Proteins/metabolism , Molecular Docking Simulation , Triterpenes
10.
J Chem Inf Model ; 64(10): 4102-4111, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38712852

ABSTRACT

The perception of bitter and sweet tastes is a crucial aspect of human sensory experience. Concerns over the long-term use of aspartame, a widely used sweetener suspected of carcinogenic risks, highlight the importance of developing new taste modifiers. This study utilizes Large Language Models (LLMs) such as GPT-3.5 and GPT-4 for predicting molecular taste characteristics, with a focus on the bitter-sweet dichotomy. Employing random and scaffold data splitting strategies, GPT-4 demonstrated superior performance, achieving an impressive 86% accuracy under scaffold partitioning. Additionally, ChatGPT was employed to extract specific molecular features associated with bitter and sweet tastes. Utilizing these insights, novel molecular compounds with distinct taste profiles were successfully generated. These compounds were validated for their bitter and sweet properties through molecular docking and molecular dynamics simulation, and their practicality was further confirmed by ADMET toxicity testing and DeepSA synthesis feasibility. This research highlights the potential of LLMs in predicting molecular properties and their implications in health and chemical science.


Subject(s)
Molecular Docking Simulation , Molecular Dynamics Simulation , Taste , Humans , Sweetening Agents/chemistry , Sweetening Agents/metabolism
11.
Int Immunopharmacol ; 135: 112295, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38776852

ABSTRACT

Aspartame, an artificial sweetener, is consumed by millions of people globally. There are multiple reports of aspartame and its metabolites affecting cognitive functions in animal models and humans, which include learning problems, headaches, seizures, migraines, irritable moods, anxiety, depression, and insomnia. These cognitive deficits and associated symptoms are partly attributed to dysregulated excitatory and inhibitory neurotransmitter balance due to aspartate released from aspartame, resulting in an excitotoxic effect in neurons, leading to neuronal damage. However, microglia, a central immunocompetent cell type in brain tissue and a significant player in inflammation can contribute to the impact. Microglia rapidly respond to changes in CNS homeostasis. Aspartame consumption might affect the microglia phenotype directly via methanol-induced toxic effects and indirectly via aspartic acid-mediated excitotoxicity, exacerbating symptoms of cognitive decline. Long-term oral consumption of aspartame thus might change microglia's phenotype from ramified to activated, resulting in chronic or sustained activation, releasing excess pro-inflammatory molecules. This pro-inflammatory surge might lead to the degeneration of healthy neurons and other glial cells, impairing cognition. This review will deliberate on possible links and research gaps that need to be explored concerning aspartame consumption, ecotoxicity and microglia-mediated inflammatory cognitive impairment. The study covers a comprehensive analysis of the impact of aspartame consumption on cognitive function, considering both direct and indirect effects, including the involvement of microglia-mediated neuroinflammation. We also propose a novel intervention strategy involving tryptophan supplementation to mitigate cognitive decline symptoms in individuals with prolonged aspartame consumption, providing a potential solution to address the adverse effects of aspartame on cognitive function.


Subject(s)
Aspartame , Cognitive Dysfunction , Microglia , Microglia/drug effects , Microglia/immunology , Humans , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/drug therapy , Animals , Neuroinflammatory Diseases/immunology , Neuroinflammatory Diseases/drug therapy , Neuroinflammatory Diseases/chemically induced , Sweetening Agents , Brain/drug effects , Brain/pathology , Brain/metabolism , Brain/immunology
12.
PLoS One ; 19(5): e0298239, 2024.
Article in English | MEDLINE | ID: mdl-38691547

ABSTRACT

The sweet taste receptor, TAS1R2-TAS1R3, is expressed in taste bud cells, where it conveys sweetness, and also in intestinal enteroendocrine cells, where it may facilitate glucose absorption and assimilation. In the present study, our objective was to determine whether TAS1R2-TAS1R3 influences glucose metabolism bidirectionally via hyperactivation with 5 mM sucralose (n = 12) and inhibition with 2 mM sodium lactisole (n = 10) in mixture with 75 g glucose loads during oral glucose tolerance tests (OGTTs) in healthy humans. Plasma glucose, insulin, and glucagon were measured before, during, and after OGTTs up to 120 minutes post-prandially. We also assessed individual participants' sweet taste responses to sucralose and their sensitivities to lactisole sweetness inhibition. The addition of sucralose to glucose elevated plasma insulin responses to the OGTT (F(1, 11) = 4.55, p = 0.056). Sucralose sweetness ratings were correlated with early increases in plasma glucose (R2 = 0.41, p<0.05), as well as increases in plasma insulin (R2 = 0.38, p<0.05) when sucralose was added to the OGTT (15 minute AUC). Sensitivity to lactisole sweetness inhibition was correlated with decreased plasma glucose (R2 = 0.84, p<0.01) when lactisole was added to the OGTT over the whole test (120 minute AUC). In summary, stimulation and inhibition of the TAS1R2-TAS1R3 receptor demonstrates that TAS1R2-TAS1R3 helps regulate glucose metabolism in humans and may have translational implications for metabolic disease risk.


Subject(s)
Benzene Derivatives , Blood Glucose , Glucose Tolerance Test , Insulin , Receptors, G-Protein-Coupled , Sucrose , Sucrose/analogs & derivatives , Humans , Receptors, G-Protein-Coupled/metabolism , Male , Adult , Female , Sucrose/metabolism , Blood Glucose/metabolism , Insulin/metabolism , Insulin/blood , Taste/physiology , Young Adult , Thiazoles/pharmacology , Glucose/metabolism , Glucagon/metabolism , Glucagon/blood , Sweetening Agents/pharmacology
13.
Endocrinol Diabetes Metab ; 7(3): e00482, 2024 May.
Article in English | MEDLINE | ID: mdl-38556697

ABSTRACT

BACKGROUND: Stevioside (SV) with minimal calories is widely used as a natural sweetener in beverages due to its high sweetness and safety. However, the effects of SV on glucose uptake and the pyruvate dehydrogenase kinase isoenzyme (PDK4) as an important protein in the regulation of glucose metabolism, remain largely unexplored. In this study, we used C2C12 skeletal muscle cells that was induced by palmitic acid (PA) to assess the effects and mechanisms of SV on glucose uptake and PDK4. METHODS: The glucose uptake of C2C12 cells was determined by 2-NBDG; expression of the Pdk4 gene was measured by quantitative real-time PCR; and expression of the proteins PDK4, p-AMPK, TBC1D1 and GLUT4 was assessed by Western blotting. RESULTS: In PA-induced C2C12 myotubes, SV could significantly promote cellular glucose uptake by decreasing PDK4 levels and increasing p-AMPK and TBC1D1 levels. SV could promote the translocation of GLUT4 from the cytoplasm to the cell membrane in cells. Moreover, in Pdk4-overexpressing C2C12 myotubes, SV decreased the level of PDK4 and increased the levels of p-AMPK and TBC1D1. CONCLUSION: SV was found to ameliorate PA-induced abnormal glucose uptake via the PDK4/AMPK/TBC1D1 pathway in C2C12 myotubes. Although these results warranted further investigation for validation, they may provide some evidence of SV as a safe natural sweetener for its use in sugar-free beverages to prevent and control T2DM.


Subject(s)
AMP-Activated Protein Kinases , Diterpenes, Kaurane , Glucosides , Palmitic Acid , Palmitic Acid/metabolism , Palmitic Acid/pharmacology , Pyruvate Dehydrogenase Acetyl-Transferring Kinase/metabolism , AMP-Activated Protein Kinases/metabolism , AMP-Activated Protein Kinases/pharmacology , Muscle, Skeletal/metabolism , Glucose/metabolism , Glucose/pharmacology , Muscle Fibers, Skeletal/metabolism , Sweetening Agents/pharmacology , Sweetening Agents/metabolism
14.
Molecules ; 29(7)2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38611906

ABSTRACT

Steviosides extracted from the leaves of the plant Stevia rebaudiana are increasingly used in the food industry as natural low-calorie sweeteners. Phthalates in food are often assumed to arise from food containers or packaging materials. Here, experiments were carried out to identify the potential sources of DMP, DBP, DIBP, and DEHP in the leaves of stevioside through investigation of their content in native stevioside tissues, soils, and associated agronomic materials. The results show that phthalate contamination was present in all the samples tested, and the influence of regional factors at the provincial level on the content of plasticizers in stevia leaves was not significant. Phthalates in stevia leaves can be absorbed into the plant body through leaves and roots. Using resin removal, the phthalate content in stevioside glycosides was reduced to less than 0.05 ppm, and some indicators were far lower than the limit standard in EU food.


Subject(s)
Diterpenes, Kaurane , Glucosides , Phthalic Acids , Stevia , Technology , Sweetening Agents
15.
Food Funct ; 15(8): 4527-4537, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38576413

ABSTRACT

Artificial sweeteners (ASs) have been widely added to food and beverages because of their properties of low calories and sweet taste. However, whether the consumption of ASs is causally associated with cancer risk is not clear. Here, we utilized the two-sample Mendelian randomization (MR) method to study the potential causal association. Genetic variants like single-nucleotide polymorphisms (SNPs) associated with exposure (AS consumption) were extracted from a genome-wide association study (GWAS) database including 64 949 Europeans and the influence of confounding was removed. The outcome was from 98 GWAS data and included several types of cancers like lung cancer, colorectal cancer, stomach cancer, breast cancer, and so on. The exposure-outcome SNPs were harmonized and then MR analysis was performed. The inverse-variance weighted (IVW) with random effects was used as the main analytical method accompanied by four complementary methods: MR Egger, weighted median, simple mode, and weighted mode. Sensitivity analyses consisted of heterogeneity, pleiotropy, and leave-one-out analysis. Our results demonstrated that ASs added to coffee had a positive association with high-grade and low-grade serous ovarian cancer; ASs added to tea had a positive association with oral cavity and pharyngeal cancers, but a negative association with malignant neoplasm of the bronchus and lungs. No other cancers had a genetic causal association with AS consumption. Our MR study revealed that AS consumption had no genetic causal association with major cancers. Larger MR studies or RCTs are needed to investigate small effects and support this conclusion.


Subject(s)
Genome-Wide Association Study , Mendelian Randomization Analysis , Neoplasms , Polymorphism, Single Nucleotide , Sweetening Agents , Humans , Female , Neoplasms/genetics , Sweetening Agents/adverse effects , Tea , Coffee , Ovarian Neoplasms/genetics , Risk Factors
16.
Invest Ophthalmol Vis Sci ; 65(4): 5, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38558091

ABSTRACT

Purpose: We aimed to determine the impact of artificial sweeteners (AS), especially saccharin, on the progression and treatment efficacy of patients with neovascular age-related macular degeneration (nAMD) under anti-vascular endothelial growth factor (anti-VEGF-A) treatment. Methods: In a cross-sectional study involving 46 patients with nAMD undergoing intravitreal anti-VEGF therapy, 6 AS metabolites were detected in peripheral blood using liquid chromatography - tandem mass spectrometry (LC-MS/MS). Disease features were statistically tested against these metabolite levels. Additionally, a murine choroidal neovascularization (CNV) model, induced by laser, was used to evaluate the effects of orally administered saccharin, assessing both imaging outcomes and gene expression patterns. Polymerase chain reaction (PCR) methods were used to evaluate functional expression of sweet taste receptors in a retinal pigment epithelium (RPE) cell line. Results: Saccharin levels in blood were significantly higher in patients with well-controlled CNV activity (P = 0.004) and those without subretinal hyper-reflective material (P = 0.015). In the murine model, saccharin-treated mice exhibited fewer leaking laser scars, lesser occurrence of bleeding, smaller fibrotic areas (P < 0.05), and a 40% decrease in mononuclear phagocyte accumulation (P = 0.06). Gene analysis indicated downregulation of inflammatory and VEGFR-1 response genes in the treated animals. Human RPE cells expressed taste receptor type 1 member 3 (TAS1R3) mRNA and reacted to saccharin stimulation with changes in mRNA expression. Conclusions: Saccharin appears to play a protective role in patients with nAMD undergoing intravitreal anti-VEGF treatment, aiding in better pathological lesion control and scar reduction. The murine study supports this observation, proposing saccharin's potential in mitigating pathological VEGFR-1-induced immune responses potentially via the RPE sensing saccharin in the blood stream.


Subject(s)
Choroidal Neovascularization , Macular Degeneration , Humans , Mice , Animals , Vascular Endothelial Growth Factor Receptor-1 , Saccharin/therapeutic use , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , Sweetening Agents , Cross-Sectional Studies , Chromatography, Liquid , Tandem Mass Spectrometry , Choroidal Neovascularization/metabolism , Macular Degeneration/metabolism , RNA, Messenger/genetics , Intravitreal Injections , Angiogenesis Inhibitors/therapeutic use
17.
Molecules ; 29(8)2024 Apr 13.
Article in English | MEDLINE | ID: mdl-38675593

ABSTRACT

Rare sugars are known for their ability to suppress postprandial blood glucose levels. Therefore, oligosaccharides and disaccharides derived from rare sugars could potentially serve as functional sweeteners. A disaccharide [α-d-allopyranosyl-(1→2)-ß-d-psicofuranoside] mimicking sucrose was synthesized from rare monosaccharides D-allose and D-psicose. Glycosylation using the intermolecular aglycon delivery (IAD) method was employed to selectively form 1,2-cis α-glycosidic linkages of the allopyranose residues. Moreover, ß-selective psicofuranosylation was performed using a psicofuranosyl acceptor with 1,3,4,6-tetra-O-benzoyl groups. This is the first report on the synthesis of non-reducing disaccharides comprising only rare d-sugars by IAD using protected ketose as a unique acceptor; additionally, this approach is expected to be applicable to the synthesis of functional sweeteners.


Subject(s)
Disaccharides , Fructose , Glucose , Sucrose , Disaccharides/chemistry , Disaccharides/chemical synthesis , Sucrose/chemistry , Glycosylation , Sweetening Agents/chemistry
18.
Biochem Biophys Res Commun ; 711: 149921, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38603831

ABSTRACT

Artificial sweeteners, which contain no or few calories, have been widely used in various foods and beverages, and are regarded as safe alternatives to sugar by the Food and Drug Administration. While several studies suggest that artificial sweeteners are not related to cancer development, some research has reported their potential association with the risk of cancers, including hepatocellular carcinoma (HCC). Here, we investigated whether acesulfame potassium (Ace K), a commonly used artificial sweetener, induces immune evasion of HCC cells by upregulating programmed death ligand-1 (PD-L1). Ace K elevated the protein levels of PD-L1 in HCC cells without increasing its mRNA levels. The upregulation of PD-L1 protein levels in HCC cells by Ace K was induced by attenuated autophagic degradation of PD-L1, which was mediated by the Ace K-stimulated ERK1/2-mTORC1 signaling pathway. Ace K-induced upregulation of PD-L1 attenuated T cell-mediated death of HCC cells, thereby promoting immune evasion of HCC cells. In summary, the present study suggests that Ace K promotes HCC progression by upregulating the PD-L1 protein level.


Subject(s)
Autophagy , B7-H1 Antigen , Carcinoma, Hepatocellular , Liver Neoplasms , Thiazines , Up-Regulation , B7-H1 Antigen/metabolism , B7-H1 Antigen/genetics , Humans , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/genetics , Autophagy/drug effects , Up-Regulation/drug effects , Thiazines/pharmacology , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/genetics , Cell Line, Tumor , Sweetening Agents/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Mechanistic Target of Rapamycin Complex 1/metabolism , MAP Kinase Signaling System/drug effects
19.
Chemosphere ; 356: 141893, 2024 May.
Article in English | MEDLINE | ID: mdl-38582168

ABSTRACT

Acesulfame (ACE), sucralose (SUC), cyclamate (CYC), and saccharin (SAC) are widely used artificial sweeteners that undergo negligible metabolism in the human body, and thus ubiquitously exist in wastewater treatment plants (WWTPs). Due to their persistence in WWTPs, ACE and SUC are found in natural waters globally. Wastewater samples were collected from the primary influent, primary effluent, secondary effluent, and final effluent of a WWTP in Alberta, Canada between August 2022 and February 2023, and the artificial sweeteners concentrations were measured by LC-MS/MS. Using wastewater-based epidemiology, the daily per capita consumption of ACE in the studied wastewater treatment plant catchment was estimated to be the highest in the world. Similar to other studies, the removal efficiency in WWTP was high for SAC and CYC, but low or even negative for SUC. However, ACE removal remained surprisingly high (>96%), even in the cold Canadian winter months. This result may indicate a further adaptation of microorganisms capable of biodegrading ACE in WWTP. The estimated per capita discharge into the environment of ACE, CYC, and SAC is low in Alberta due to the prevalent utilization of secondary treatment throughout the province, but is 17.4-18.8 times higher in Canada, since only 70.3% of total discharged wastewater in Canada undergoes secondary treatment.


Subject(s)
Sucrose/analogs & derivatives , Sweetening Agents , Thiazines , Waste Disposal, Fluid , Wastewater , Water Pollutants, Chemical , Wastewater/chemistry , Sweetening Agents/analysis , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/metabolism , Alberta , Thiazines/analysis , Saccharin/analysis , Environmental Monitoring , Biodegradation, Environmental , Tandem Mass Spectrometry , Sucrose/analysis , Sucrose/metabolism
20.
Int. microbiol ; 27(2): 581-596, Abr. 2024. graf
Article in English | IBECS | ID: ibc-232303

ABSTRACT

Erythritol has been produced by various microorganisms including Yarrowia, Moniliella, Aureobasidium, and Candida strains. Due to its relatively high price, erythritol sweetener is used lesser than other polyols despite having many advantages. Therefore, in this study, Moniliella pollinis strain was improved for erythritol production by chemical mutagenesis and subsequently screening for cost-effective carbon sources for the enhanced erythritol yield. M. pollinis was subjected to N-methyl N-nitro N-nitroso guanidine (NTG), ethyl methyl sulfonate (EMS), and UV mutagenesis for improved erythritol production. The fmutant strains were evaluated for enhanced erythritol production medium optimization by using different carbon substrates at the shake flask level. To enhance the production of erythritol and statistical media, optimization was carried out using a central composite design (CCD). Among 198 isolated mutants, Mutant-58 strain generated by EMS mutagenesis was selected for further assessment. The Mutant-58 strain showed significant morphological changes as compared to the parent strain. Furthermore, statistically optimized media composition resulted in the higher production of erythritol (91.2 ± 3.4 g/L) with a yield of 40.7 ± 3.4 % in shake flask experiments. The optimized medium composition for erythritol production constitutes (g/L) 225 jaggery, 4.4 yeast extract (YE), 4.4 KH2PO4, 0.31 MgSO4, and pH 5.5. The present study demonstrated strain improvement, media, and process optimization resulting in a 30% increase in the erythritol production in the Mutant-58 as compared to the parent strain. This is also the first instance where jaggery has been used as a cost-effective carbon source alternative to glucose for industrial-scale erythritol production. (AU)


Subject(s)
Erythritol , Aquatic Microorganisms , Yarrowia , Candida , Sweetening Agents
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