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Jamu is one of the traditional medicines because most herbal medicine uses natural ingredients or plants. One of the safety of herbal medicine is the absence of abuse such as the addition of artificial sweeteners in the form of cyclamate. Cyclamate is one of the artificial sweeteners that has a sweetness level 30 times higher than natural sweeteners. Excessive use of cyclamate will cause cancer and tumors. The purpose of this study is to determine the presence or absence of cyclamate content and levels in ready-to-drink herbal medicine without a brand sold in the Pamekasan City market. This research was conducted qualitatively with precipitation methods and quantitative with gravimetric methods. From qualitative research, the results of sample A found a white precipitate which indicates a positive sample containing cyclamate. While samples B and C found no deposits indicating that the sample was negative cyclamate. Furthermore, a positive sample is carried out quantitative testing. In determining cyclamate levels, sodium cyclamate levels in sample A were obtained at 4.8047 g/kg. so that the serving rate or per 1 bottle of herbal medicine contains 115.312 g/0.6 kg and this exceeds the threshold determined by BPOM Regulations which is 1.25 g/kg. The conclusion of this study is that 1 out of 3 positive samples contains cyclamate with levels that exceed the threshold determined by BPOM RI No. 32 of 2019. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the effects of sodium cyclamate and saccharine combination on the overall hematological parameters and brain catalase activity in Wistar rats. During a period of 8 weeks, the animals were given the artificial sweeteners in a low (L; 15,4 mg/mL) and high dose (H; 22 mg/mL). Additionally, to determine whether vitamin C can attenuate the changes induced by high doses, it was administered to a third group of animals (H + vit C; 22 mg/mL+25 mg/mL). Decreased hematocrit and hemoglobin values, low erythrocyte count and mean cell volume in the groups treated with the artificial sweeteners were the main hematological changes causing microcytic anemia. Catalase activity in brain tissue decreased with the increase of the sweeteners dose, which clearly indicates the induction of oxidative stress. Further on, catalase was significantly increased in the H + vit C group compared to the H group but there was no significant difference compared to controls. Collectively, these results suggest that sodium cyclamate and saccharine induced considerable alterations in the hematology, an increased consumption of catalase and a high efficiency of vitamin C to ameliorate the oxidative stress. [ABSTRACT FROM AUTHOR]

Artificial sweeteners (ASs) entered the environments after application and emissions. Recent studies showed that some ASs had obesogenic risks. However, it remained unclear whether such risks are common and how they provoke such effects. Presently, the effects of 8 widely used ASs on lipid accumulation were measured in Caenorhabditis elegans. Potential mechanisms were explored with feeding and locomotion behavior, lipid metabolism and neural regulation. Results showed that acesulfame (ACE), aspartame (ASP), saccharin sodium (SOD), sucralose (SUC) and cyclamate (CYC) stimulated lipid accumulation at μg/L levels, showing obesogenic potentials. Behavior investigation showed that ACE, ASP, SOD, SUC and CYC biased more feeding in the energy intake aspect against the locomotion in the energy consumption one. Neotame (NEO), saccharin (SAC) and alitame (ALT) reduced the lipid accumulation without significant obesogenic potentials in the present study. However, all 8 ASs commonly disturbed enzymes (e.g., acetyl-CoA carboxylase) in lipogenesis and those (e.g., carnitine palmitoyl transferase) in lipolysis. In addition, ASs disturbed PPARγ (via expressions of nhr-49), TGF-β/DAF-7 (daf-7) and SREBP (sbp-1) pathways. Moreover, they also interfered neurotransmitters including serotonin (5-HT), dopamine (DA) and acetylcholine (ACh), with influences in Gsα (e.g., via expressions of gsα-1, ser-7), glutamate (e.g., mgl-1), and cGMP-dependent signaling pathways (e.g., egl-4). In summary, environmental ASs commonly disturbed neural regulation connecting behavior and lipid metabolism, and 5 out of 8 showed clear obesogenic potentials. ENVIRONMENTAL IMPLICATION: Artificial sweeteners (ASs) are become emerging pollutants after wide application and continuous emission. Recent studies showed that some environmental ASs had obesogenic risks. The present study employed Caenorhabditis elegans to explore the influences of 8 commonly used ASs on lipid metabolisms and also the underlying mechanisms. Five out of 8 ASs stimulated lipid accumulation at μg/L levels, and they biased energy intake against energy consumption. The other three ASs reduced the lipid accumulation. ASs commonly disturbed lipogenesis and lipolysis via PPARγ, TGF-β and SREBP pathways, and also influenced neurotransmitters with Gsα, glutamate and cGMP-dependent signaling pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Observational investigations into the health impacts of low-calorie sweeteners (LCSs) in humans fail to adequately identify or fully characterize LCS consumption.Objectives: We aimed to utilize a novel biomarker approach to investigate exposure to 5 LCSs and to test whether reported low-calorie sweetened beverage (LCSB) consumption effectively identifies exposure to LCSs in adults.Methods: In this cross-sectional analysis, 2 population studies were conducted in adults. Urinary excretions of 5 LCSs, namely acesulfame-K, saccharin, cyclamate, sucralose, and steviol glycosides, were simultaneously determined using LC tandem-MS. In Study 1, previously collected 24-h urine samples (n = 357) were analyzed. In Study 2, previously collected 24-h urine samples (n = 79) were analyzed to compare urinary excretions of LCSs with self-reported LCSB consumption for identifying LCS exposure. Exposure to LCSs was characterized using descriptive statistics and chi-square tests were performed to assess associations between age-groups and LCS excretion, and to assess the proportion of individuals identified as LCS consumers using biomarker data or reported LCSB consumption.Results: A total of 341 adults (45% men) and 79 adults (39% men) were included in the final analysis of Studies 1 and 2, respectively. In Study 1, >96% of samples contained ≥1 LCS and almost 60% contained ≥3 LCSs. A greater proportion of younger adults (<40 y old) excreted ≥3 LCSs than older adults (>40 y old) (P < 0.001). In Study 2, a much higher prevalence of LCS consumption was observed using biomarker data (92%) than reported LCSB consumption (6%) (P < 0.001).Conclusions: This work indicates widespread exposure to LCSs, suggesting that population-based research to date into LCS exposure and health may be flawed. Therefore, a urinary biomarker approach offers considerable potential for more robust investigations in this area. [ABSTRACT FROM AUTHOR]

In this work, we investigated the reaction of cyclamate with hypochlorous acid (HOCl) in simulated gastric juice. The reaction products were detected by high-performance liquid chromatography diode array detection (HPLC-DAD) and ultra-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS). We also explored the changes in product concentration as a function of reaction time, cyclamate and HOCl concentrations. Cyclamate reacted with hypochlorous acid instantly in the simulated gastric fluid. N, N-dichlorcyclohexylamine and cyclohexylamine were both detected when the HOCl concentration was at millimole. Cyclohexylamine can only be found when HOCl concentration was at micromole. N, N-dichlorcyclohexylamine and cyclohexylamine concentrations both increased when cyclamate concentration increased under the millimole level of HOCl. As an important reactive oxygen species, hypochlorous acid (HClO) is produced in various physiological processes. The abnormal rise of the HClO level is associated with many inflammatory diseases. Chronic gastritis associated with Helicobacter pylori is a multistep, progressive, life-long inflammation. So, chronic gastritis infected with H. pylori may cause cyclamate metabolizing into cyclohexylamine in vivo.

Dietary-derived substances possess significant potential as anthropogenic markers owing to the large consumption and different intake habit. To investigate and evaluate such markers, wastewater samples from 35 wastewater treatment plants across 29 Chinese cities were collected to analyze artificial sweeteners (acesulfame and cyclamate) and natural spicy compounds (capsaicin and dihydrocapsaicin). Acesulfame (mean: 14.6 μg/L), cyclamate (mean: 24.3 μg/L), and capsaicin (mean: 101 ng/L) can be further investigated as anthropogenic markers due to their high detection frequency at high concentrations. Spatial use patterns revealed that acesulfame (5.31 g/d/1000 inhabitants (inh)) and cyclamate (8.16 g/d/1000 inh) use in northern China notably surpassed that in southern China (1.79 g/d/1000 inh and 3.23 g/d/1000 inh, p < 0.05). Conversely, chili pepper use was significantly higher (p < 0.05) in southern China (6702 g/d/1000 inh) than in northern China (2751 g/d/1000 inh), signifying a preference for sweetness in the northern regions and a predilection for spiciness in the southern regions. The total annual use of acesulfame (1842 t), cyclamate (3110 t), and chili (18.4 million tonnes) in China was estimated by this study, which was close to the national statistical production. In addition, sweetener use was negatively associated with the elderly population ratio, suggesting that the elderly population might not consume sweet foods. This study reveals the dietary sources of anthropogenic markers, highlighting the need for further research on the environmental implications of such markers., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Mahonia bealei (Fortune) Carrière (M. bealei) is a traditional medicine widely used by the Hmong community in Guizhou. It possesses diverse biological activities and shows promise in cancer treatment; however, contemporary pharmacological research in this area is lacking., Aims of the Study: This study aimed to investigate the effects and underlying mechanisms of M. bealei on alcoholic hepatocellular carcinoma (HCC)., Materials and Methods: We initially employed the LC-MS/MS method to identify the compounds present in M. bealei serum. Subsequently, its potential targets were predicted using public databases. Bioinformatics and network pharmacology approaches, such as univariate Cox regression and random forest (RF) algorithms, were utilized to identify differentially expressed genes (DEGs) associated with the prognosis of alcoholic HCC. Survival curve and receiver operating characteristic (ROC) analyses were conducted using alcoholic HCC-related data from TCGA and GEO to determine the diagnostic value of the identified DEGs. Molecular docking using the CDOCKER approach based on CHARMm was performed to validate the affinity between the predictive compounds and targets. Additionally, we evaluated the impact of M. bealei on cell proliferation, migration, and conducted western blot assays., Results: The LC-MS/MS approach identified 17 therapeutic components and predicted 483 component-related targets, of which 63 overlapped with alcoholic HCC targets and were considered potential therapeutic targets. GO and KEGG pathway analysis revealed significant associations between the 63 overlapping targets and alcoholic HCC progression. Through various approaches in the Cytoscape 3.9.0 software, we confirmed 9 hub genes (CDK1, CXCR4, DNMT1, ESR1, KIT, PDGFRB, SERPINE1, TOP2A, and TYMS) as core targets. TOP2A and CDK1 genes were identified as advantageous for diagnosing alcoholic HCC using univariate Cox regression, RF, survival curve, and ROC analysis. Molecular docking analysis demonstrated strong binding affinity between key bioactive components cyclamic acid, perfluoroalkyl carboxylic acid, perfluorosulfonic acid, alpha-linolenic acid, adenosine receptor antagonist (CGS 15943), and Prodigiosin and TOP2A and CDK1. In vitro experiments confirmed that M. bealei significantly suppressed cell proliferation and migration of HepG2 cells, while downregulating TOP2A and CDK1 expression., Conclusion: This study highlights the potential of M. bealei as a natural medicine for the treatment of alcoholic HCC. Six compounds (cyclamic acid, perfluoroalkylic carboxylic acids, perfluorosulfonic acid, alpha-linolenic acid, adenosine receptor antagonist (CGS 15943), and Prodigiosin) present in M. bealei serum may exhibit therapeutic effects against alcoholic HCC by downregulating CDK1 and TOP2A expression levels in vitro., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Abstract Low/no-calorie sweeteners (LNCS) are continually under the spotlight in terms of their safety and benefits; in 2014 a study was published linking LNCS to an enhanced risk of glucose intolerance through modulation of the gut microbiota. In response, an in-depth review of the literature was undertaken to evaluate the major contributors to potential changes in the gut microbiota and their corresponding sequelae, and to determine if consuming LNCS (e.g., acesulfame K, aspartame, cyclamate, neotame, saccharin, sucralose, steviol glycosides) contributes to changes in the microbiome based on the data reported in human and animal studies. A few rodent studies with saccharin have reported changes in the gut microbiome, but primarily at high doses that bear no relevance to human consumption. This and other studies suggesting an effect of LNCS on the gut microbiota were found to show no evidence of an actual adverse effect on human health. The sum of the data provides clear evidence that changes in the diet unrelated to LNCS consumption are likely the major determinants of change in gut microbiota numbers and phyla, confirming the viewpoint supported by all the major international food safety and health regulatory authorities that LNCS are safe at currently approved levels. Highlights • Composition of the human gut microbiota is influenced by many dietary factors. • Literature review identified in vivo studies on sweeteners and gut microbiota. • Impact on microbiota confounded by uncontrolled background diet. • Sweetener exposures typically exceeded ADI; therefore, human relevance limited. • Current studies show no evidence of adverse effects of sweeteners on gut microbiota. [ABSTRACT FROM AUTHOR]

Abstract This is the first comprehensive study on the input, occurrence, and distribution of artificial sweeteners (ASs) in coastal wastewater treatment plants (WWTPs) and their receiving coastal waters. Acesulfame (ACE), aspartame (ASP), cyclamate (CYC), saccharine (SAC), and sucralose (SUC) were monitored for 6 months in Cadiz Bay (SW Spain). ASP was always detected at <0.1 μg L−1 and removal efficiencies were >90% for SAC and CYC. Higher ACE removal efficiencies were observed during warmer months. Persistence of ACE and SUC was observed in both WWTPs and their receiving coastal surface waters, where values up to 0.6 and 3 μg L−1 were measured, respectively. The highest concentrations were measured in a sewage-impacted estuary located in the north of the bay, where conservative behavior was confirmed. The source specificity and recalcitrance of ACE and SUC make them suitable for being used as sewage-pollution markers in coastal environments. Graphical abstract Unlabelled Image Highlights • Removals of acesulfame during sewage treatment increased during warmer months. • The input for artificial sweeteners rose at one wastewater plant due to tourism. • Sucralose was detected at the highest concentrations (3 μg L−1) in coastal waters. • Removal efficiencies were between 92 and 100% for aspartame and saccharin. • Conservative behavior of acesulfame and sucralose was confirmed in an estuary. [ABSTRACT FROM AUTHOR]

From the system metal-cyclam-condensed phosphate is isolated the first complex of {(H 3 O + ) 2 [Cu(II)(μ-P 4 O 12 )(cyclam)]} n (1) . This complex was characterized by X-ray diffraction (XRD), spectroscopy (diffuse reflectance, UV–Vis and FT-IR) and thermal analysis (DTA/TGA). The solved molecular structure of 1 revealed one rare 1D-anionic polymeric copper(II)-complex, {[Cu(II)(μ-P 4 O 12 )(cyclam)] 2- } n , involving two distinct ring ligands (cyclam / cyclotetraphosphate), in which a new coordination mode of the P 4 O 12 4 − was observed. The counterions (H 3 O + ) ensure the connection between 1D-polymers by acting as donor in a strong "charge-assisted" hydrogen bonds with P 4 O 12 rings leading to 2D-supramolecular frameworks arranged in -A-B-A- fashion. The 2D-supramolecular network is stabilized by O/N-H…O interactions whereas the van der Waals contacts play a key role in the consolidation of the 3D packing as verified by Hirshfeld surface analysis in combination with 2D fingerprint plots. The biochemical properties of 1 was also evaluated via DDPH, ABTS, hydroxyl radical scavengers and ferric reducing power (FRP) showing promising antioxidant activities which has been clarified by means of the cyclic voltammetric study. [ABSTRACT FROM AUTHOR]

This research investigated the intakes of six intense sweeteners: acesulfame-K (E950), aspartame (E951), cyclamate (E952), saccharin (E954), sucralose (E955), and steviol glycosides (E960) in the diets of Irish adults, using data from the National Adult Nutrition Survey. A food label survey that included products currently available on the Irish market supplemented the analysis. Sweetener intakes were investigated using three different exposure scenarios; beginning with a crude assessment which assumed that all foods permitted to contain the additives of interest always did contain them, and at their maximum permitted level (Tier 1). Refined assessments estimated intakes of the six sweeteners using food consumption data up to brand level with additive occurrence data from a survey of products currently available on the Irish market (Tier 2) and sweetener concentration data (Tier 3). Results of all exposure assessment scenarios demonstrate that intakes of each of the sweeteners of interest by the total population were below the relevant ADI level (mg kg−1 bodyweight−1), even by high consumers (P99). The three sweeteners consumed in highest amounts were acesulfame-k, aspartame, and sucralose. The main sources of these sweeteners in the diet were ‘cider and perry’, ‘energy reduced and no added sugar (ER and NAS) carbonated flavoured drinks’, ‘table-top sweeteners’, ‘dairy products’, ‘solid food supplements’, and ‘sauces’. Intakes of the six intense sweeteners are currently not a concern among Irish adults. However, exposure to these chemicals should be monitored on a regular basis due to evolving market and consumption patterns. [ABSTRACT FROM AUTHOR]

This paper reports on a high-throughput headspace gas chromatographic method (HS-GC) for the determination of nitrite content in water sample, based on GC measurement of cyclohexene produced from the reaction between nitrite and cyclamate in a closed vial. The method has a relative standard deviation of <3.5%; The differences between the results of the nitrite measurements obtained by this method and those of a reference method were less than 5.8% and the recoveries of the method were in the range of 94.8–102% (for a spiked nitrite content range from 0.002 to 0.03 mg/L). The limit of detection of the method was 0.46 μg L −1 . Due to an overlapping mode in the headspace auto-sampler system, the method can provide an automated and high-throughput nitrite analysis for the surface water samples. In short, the present HS-GC method is simple, accurate, and sensitive, and it is very suitable to be used in the batch sample testing. [ABSTRACT FROM AUTHOR]

Pig farm is an important potential source for artificial sweeteners (ASs) in the environment due to their wide use as additives in pig feed. The objective of this study was to evaluate the fate of typical ASs in pig farm and neighboring farmland. For this purpose, the levels of four typical artificial ASs, i.e. saccharin (SAC), cyclamate (CYC), acesulfame (ACE) and sucralose (SUC), in pig feed and manure from a pig farm and water samples from an on-farm wastewater treatment plant (WWTP) in Tianjin, China were measured and the mass loadings and removal efficiencies were assessed. Moreover, the levels of ASs in different layers of soil and vegetables in neighboring farmland that received manure fertilizers and wastewater from the farm were consecutively monitored for 60–80 days. The SAC, CYC and ACE were widely determined in all kinds of the samples, while SUC was only found in few soil samples. The mass loadings of the ASs in pig feed were estimated up to 311 kg/year for SAC, 59.1 kg/year for CYC, and 17.1 kg/year for ACE, respectively. The fractions of the total mass of ASs excreted via manure were estimated to be 36.0% for SAC, 59.4% for CYC, and 36.7% for ACE as compared to those in pig feed. High removal efficiencies (> 90%) of ASs in the on-farm WWTP was achieved. In greenhouse soils, CYC, SAC, ACE, and SUC were degraded quickly, with half-lives of 4.3–5.9 d, 2.7–4.2 d, 8.4–12.3 d, and 7.3–10.8 d, respectively. Lower levels of ASs were found in deeper soil layer (20–30 cm). The ASs were considerably absorbed by plants when the ASs' concentrations were high in soil. This study presents the first comprehensive overview of ASs fate from a pig farm to the neighboring agricultural ecosystem. [ABSTRACT FROM AUTHOR]

Compound-specific standardized sampling and storage methods are not available for artificial sweeteners found in groundwater. This study aimed to understand: (1) the appropriate length of storage time for samples containing acesulfame (ACE), sucralose (SUC), saccharin (SAC), and cyclamate (CYC) in simulated groundwater (SGW); (2) conditions of their stability; and (3) which sampling materials are appropriate for sample collection. The evaluated storage conditions included acidification, headspace, exposure to light, and refrigeration; the evaluated sampling materials included steel, stainless steel, aluminum, polyvinyl chloride, polyamide (nylon), polypropylene (PharMed BPT™) tubing, styrene-ethylene-butylene co-polymer (MasterFlex™) tubing, and polytetrafluoroethylene (Teflon™) tubing. All compounds evaluated were stable in storage at 4 °C for 241 d (8 months). Concentrations of artificial sweeteners were consistently within 60% to 120% of original concentrations, except ACE and SAC that were substantially lower under acidified conditions at 25 °C after 241 d. Artificial sweetener concentrations remained nearly constant while in contact with all sampling materials except steel. SEM and TEM images showed oxidation of steel occurred; moreover, removal of all artificial sweetener compounds from aqueous solution had occurred after 289 d. These results suggest artificial sweetener analyses conducted within 14 d of sample collection produce optimal results; however, longer storage times may be acceptable under certain conditions. The results also suggest concentrations of artificial sweeteners in SGW are not affected by contact with typical well casing, sampling, and storage materials, with the exception of steel. The findings from this study will improve the use of artificial sweeteners as tracers in environmental studies. [ABSTRACT FROM AUTHOR]

A pentadentate cage-like cyclam-based fluorescent ligand has been designed, synthesized, and characterized by 1D and 2D NMR spectroscopic analysis. To further characterize the title ligand, ESI-MS, UV/Vis spectroscopy, and fluorescence experiments have been also performed. Its suitability as a chemosensor for the detection of Cu2+ ions has been successfully explored with a variety of spectroscopic techniques (i.e., ESI-MS, UV/Vis, and fluorescence). A Job's plot experiment, together with ESI-MS experiments, indicate a 1:1 stoichiometry for the binding of Cu2+ to the cyclam-based ligand. Fluorescence experiments corroborate this hypothesis. The resulting system is selective in the recognition of copper and is stable for a week, as assessed by fluorescence spectroscopy. The CuII complex has been isolated and tested as a fluorescent probe for the detection of H2S. NMR spectroscopy and ESI-MS investigations have provided evidence that H2S recognition occurs through a copper-displacement mechanism, as reported in the literature for different copper complexes. The system functions with a selective response to HS–, harnessing a concentration-dependent “turn-on” of the initial fluorescence intensity. [ABSTRACT FROM AUTHOR]

For the first time, a procedure for simultaneous determination of the main artificial sweeteners, aspartame (ASP), cyclamate (CYC), saccharin (SAC), and acesulfame-K (ACSK) by a spectroscopic method associated with the multivariate calibration is proposed. These analytes were quantified in tabletop sweeteners samples using FT-Raman spectroscopy. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used as reference method. Partial least squares (PLS), interval PLS (iPLS), and synergism PLS (siPLS) methods were evaluated in a comparative study where the selected interval models presented better results. Multivariate regression models, such as PLS, iPLS and siPLS were built and the lower root mean square errors for prediction (RMSEP) found were 0.027–0.031% w/w, 0.316–0.363% w/w, 0.082–0.184% w/w, and 0.040–0.049% w/w to ASP, CYC, SAC, and ACSK, respectively. The coefficient of determination for prediction (R 2 p ) varied between 0.978 and 0.979, 0.969–0.977, 0.952–0.994, and 0.959–0.965 for ASP, CYC, SAC and ACSK, respectively. The analysis of model's residues was made by bias and permutation tests to evaluate systematic and trend errors. The selected intervals by iPLS and siPLS were evaluated and the bands related to the vibrational modes of the analytes were assigned with the aid of density functional theory calculations (DFT). [ABSTRACT FROM AUTHOR]

A novel method for determination of sodium cyclamate in foods was developed. In this method, a syringe was loaded with the homogeneous mixture of the sample, KMnO 4 powder and silica dispersant and used as a matrix solid phase dispersion (MSPD) reactor. As the reactor was infiltrated with small amounts of concentrated HCl, cyclamate was converted to 2-chlorocyclohexanone quickly and effectively within 5 min and determined by HPLC on a reversed-phase column using UV detection at a wavelength of 310 nm. Comparing with the traditional derivatisation in solution, the better clean-up was provided using on-cartridge derivatisation of MSPD, and much time, labor, and expense were saved. The results showed good linearity (r 2 = 0.9998) over the concentration range of 1–500 mg/L. The limit of detection (LOD) and limits of quantification (LOQ) of the cyclamate were 0.3 mg/L and 1 mg/L respectively. The recoveries ranged from 91.6% to 101.3% with the relative standard deviations (RSDs) in the range of 2.5%–4.3%. [ABSTRACT FROM AUTHOR]

Cyclamate is widely used as intense sweetener in the European Union. The absence of a maximum limit for the use of cyclamate in tabletop sweeteners and the growing demand for this type of product highlights the importance of developing robust analytical methods for the determination of its content to understand if the consumption of tabletop sweeteners can have a negative impact on human health. The present work aimed at the optimisation and validation of an high-performance liquid chromatography (HPLC) analytical method for cyclamate determination in tabletop sweeteners based on the procedure of European Standard EN 12857. The validated method was then applied to the determination of this sweetener in different types of tabletop sweeteners (liquid, powder and tablets). Both standards and samples solutions were submitted to a derivatisation procedure which converted cyclamate to N,N-dichlorocyclohexylamine. The derivatised product was separated and quantified using a reversed-phase column, a mobile phase composed of water (20%) and methanol (80%), isocratic flow of 1 ml min–1, and detection by ultraviolet spectrophotometry at a wavelength of 314 nm. The analytical method was internally validated according to the following validation parameters: working range, linearity, limits of detection and quantification, sensitivity, precision (repeatability and intermediate precision), and uncertainty. This method proved to be specific and selective for the determination of this sweetener, showing repeatability, RSDr ≤ 3%, intermediate precision, RSDR ≤ 3.3%, and recovery rates from 92% to 108% for the different tabletop sweeteners. The method uncertainty was 9.4%. The concentration of cyclamate in the samples varied significantly, from 2.9% to 73.9%, which demonstrated that a possible excessive consumption of one of the analysed sweeteners can lead to exceeding the acceptable daily intake for cyclamate. [ABSTRACT FROM AUTHOR]

Oxidation-Kinetics of cyclamate by bromamine-T (BAT) in HClO medium catalyzed by RuCl exhibits a first-order dependence on [BAT], fractional-order on both [Cyclamate] and [RuCl], and inverse fractional-order on [HClO]. RuCl catalyst accelerated the reaction by a splendid 48 times. Plausible mechanism and related rate law have been deduced. Graphical Abstract: The Stoichiometry of the reaction is: [ABSTRACT FROM AUTHOR]

High-intensity sweeteners ('sweeteners'), such as sucralose, saccharine, acesulfame, cyclamate and steviol, are replacing sugars in many food products, but biomarker-based data on their population-wide exposure, as well as analytical methods that can quantify urinary concentrations of sugars and sweeteners simultaneously, are lacking. Here, we developed and validated an ultra-pressure liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) method to quantify glucose, sucrose, fructose, sucralose, saccharine, acesulfame, cyclamate and steviol glucuronide in human urine. Urine samples were prepared by a simple dilution step containing the internal standards in water and methanol. Separation was achieved on a Shodex Asahipak NH2P-40 hydrophilic interaction liquid chromatography (HILIC) column using gradient elution. The analytes were detected using electrospray ionization in negative ion mode, and selective reaction monitoring was optimized using the [M-H]- ions. Calibration curves ranged between 34 and 19,230 ng/mL for glucose and fructose, and 1.8 to 1,026 ng/mL for sucrose and the sweeteners. The method has acceptable accuracy and precision, which depends on the application of appropriate internal standards. Storage of urine samples in lithium monophosphate gives the best overall analytical performance, and storage at room temperature without any preservatives should be avoided since this leads to reduced glucose and fructose concentrations. With the exception of fructose, all analytes were stable throughout 3 freeze-thaw cycles. The validated method was applied to human urine samples, demonstrating quantifiable concentrations of the analytes which were in the expected range. It is concluded that the method has acceptable performance to quantitatively determine dietary sugars and sweeteners in human urine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper (Marlies Diepeveen-de Bruin, Walid Maho, Marion E.C. Buso, Novita D. Naomi, Elske M. Brouwer-Brolsma, Michiel G.J. Balvers). The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Prof. Edith Feskens reports financial support was provided by European Commission. Prof. Edith Feskens reports a relationship with Royal FrieslandCampina, European Beer Institute, Kenniscentrum Suiker en Gezondheid that includes: funding grants]., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

The prevalence of obesity is increasing, and the origins of obesity and metabolic dysfunction may be traced back to fetal life. Currently, overweight pregnant women are advised to substitute sugar-sweetened beverages with diet drinks containing artificial sweeteners. Recent evidence suggests that the consumption of artificial sweeteners during pregnancy increases the risk of obesity in the child, but the mechanism is unknown. We hypothesized the transportation of artificial sweeteners across the placenta into the fetal circulation and the amniotic fluid. We included 19 pregnant women who were given an oral dose of acesulfame, cyclamate, saccharin, and sucralose immediately before a planned caesarean section. Nine women were included as controls, and they refrained from an intake of artificial sweeteners. The maternal and fetal blood and amniotic fluid were collected during the caesarean section, and concentrations of artificial sweeteners were measured using mass spectrometry. We found a linear relationship between the fetal plasma concentrations of artificial sweeteners and the maternal plasma concentrations, with adjusted coefficients of 0.49 (95% CI: 0.28-0.70) for acesulfame, 0.72 (95% CI: 0.48-0.95) for cyclamate, 0.51 (95% CI: 0.38-0.67) for saccharin, and 0.44 (95% CI: 0.33-0.55) for sucralose. We found no linear relationship between amniotic fluid and fetal plasma concentrations, but there were positive ratios for all four sweeteners. In conclusion, the four sweeteners investigated all crossed the placenta and were present in the fetal circulation and amniotic fluid.

Background: Previous studies on saccharin and cyclamate were either limited to experimental animals or lacked evaluation of their long-term consumption effects in humans., Objectives: This study evaluated the effect of chronic consumption of saccharin and cyclamate on biochemical parameters in healthy individuals and patients with type 2 diabetes mellitus., Material and Methods: Healthy and diabetic individuals were classified into two groups based on whether they consumed sweeteners or not. The participants were classified according to the amount of sweetener consumed per day and duration of consumption. Serum catalase activity, peroxynitrite, ceruloplasmin, and malondialdehyde concentrations were determined. Glycated hemoglobin, fasting glucose, creatinine, alanine transaminase, and lipid profile were also evaluated. The results suggest that saccharin and cyclamate increased HbA1C (+11.16%), MDA (+52.38%), TG (+16.74%), LDL (+13.39%), and TC/HDL (+13.11%) in healthy volunteers. Diabetic patients consuming sweeteners showed increased FSG (+17.51%), ceruloplasmin (+13.17%), and MDA (+8.92%). Diabetic patients showed a positive correlation between the number of tablets consumed per day with FSG and serum creatinine. A positive correlation was found between the duration of sweetener consumption and FSG as well as TG., Conclusion: Consumption of saccharin and cyclamate affected biochemical parameters related to metabolic functions in a time and dose-dependent manner and appear to increase oxidative stress in healthy and diabetic type 2 patients.

The sweet taste receptor plays an essential role as an energy sensor by detecting carbohydrates. However, the dynamic mechanisms of receptor activation remain unclear. Here, we describe the interactions between the transmembrane domain of the G protein-coupled sweet receptor subunit, TAS1R3, and allosteric modulators. Molecular dynamics simulations reproduced species-specific sensitivity to ligands. We found that a human-specific sweetener, cyclamate, interacted with the mouse receptor as a negative allosteric modulator. Agonist-induced allostery during receptor activation was found to destabilize the intracellular part of the receptor, which potentially interfaces with the Gα subunit, through ionic lock opening. A common human variant (R757C) of the TAS1R3 exhibited a reduced response to sweet taste, in support of our predictions. Furthermore, histidine residues in the binding site acted as pH-sensitive microswitches to modulate the sensitivity to saccharin. This study provides important insights that may facilitate the prediction of dynamic activation mechanisms for other G protein-coupled receptors., (© 2023. The Author(s).)

Tuberculosis (TB) accounted for 1.5 million deaths in 2014, and new classes of anti-TB drugs are required. We report a class of functionalized 1,8-disubstituted cyclam derivatives that display low micromolar activity against pathogenic mycobacteria. These compounds inhibit intracellular growth of Mycobacterium tuberculosis, are nontoxic to human cell lines, and are active against multidrug-resistant M. tuberculosis strains, indicating a distinct mode of action. These compounds warrant further appraisal as novel agents to control TB in humans. [ABSTRACT FROM AUTHOR]

The identification and differentiation of different sources of contamination are crucial aspects of risk assessment in water resource protection. This is especially challenging in karst environments due to their highly heterogeneous flow fields. We have investigated the use of two artificial sweeteners, cyclamate and acesulfame, as an indicator set for contamination by wastewater within the rural catchment of a karst spring. The catchment was investigated in detail to identify the sources of artificial sweeteners and quantify their impact. Spring water was analysed following two different but typical recharge events: (1) a rain-on-snow event in winter, when no wastewater overflow from the sewer system was observed, and (2) an intense rainfall event in summer triggering an overflow from a stormwater detention basin. Acesulfame, which is known to be persistent, was quantified in all spring water samples. Its concentrations decreased after the winter event with no associated wastewater spillage but increased during the summer event following a recent input of untreated wastewater. Cyclamate, which is known to be degradable, was only detected following the wastewater inflow incident. The cyclamate signal matched very well the breakthrough of faecal indicator bacteria, indicating a common origin. Knowing the input function, cyclamate was used quantitatively as a tracer in transport modelling and the impact of ‘combined sewer overflow’ on spring water quality was quantified. Signals from artificial sweeteners were compared to those from bulk parameters (discharge, electrical conductivity and turbidity) and also to those from the herbicides atrazine and isoproturon, which indicate ‘old’ and ‘fresh’ flow components, respectively, both originating from croplands. High concentration levels of the artificial sweeteners in untreated wastewater (cyclamate and acesulfame) and in treated wastewater (acesulfame only) make them powerful indicators, especially in rural settings where wastewater input is relatively low, and in karst systems where dilution is often high. [ABSTRACT FROM AUTHOR]

A set of N , N ′-disubstituted sulfamides and sodium cyclamate have been tested for their inhibitory action against six isoforms of carbonic anhydrase (CA, EC 4.2.1.1) found in the brain, that is, CA I, CA II, CA VII, CA IX, CA XII and CA XIV, some of which are involved in epileptogenesis. The biological data showed interesting results for CA VII inhibition, the isozyme thought to be a novel antiepileptic target. Strong CA VII inhibitors, with K i values in the low nanomolar–subnanomolar range were identified. Some of these derivatives showed selectivity for inhibition of CA VII versus the ubiquitous isoform CA II, for which the K i values were in the micromolar range. Molecular modeling approaches were employed to understand the binding interactions between these compounds and the two CA isoforms, since the mechanism of action of such disubstituted sulfamides was not yet investigated by means of X-ray crystallography. [ABSTRACT FROM AUTHOR]

Background: There has been an emerging concern that non-nutritive sweeteners (NNS) can increase the risk of cardiometabolic disease. Much of the attention has focused on acute metabolic and endocrine responses to NNS. To examine whether these mechanisms are operational under real-world scenarios, we conducted a systematic review and network meta-analysis of acute trials comparing the effects of non-nutritive sweetened beverages (NNS beverages) with water and sugar-sweetened beverages (SSBs) in humans. Methods: MEDLINE, EMBASE, and The Cochrane Library were searched through to January 15, 2022. We included acute, single-exposure, randomized, and non-randomized, clinical trials in humans, regardless of health status. Three patterns of intake were examined: (1) uncoupling interventions, where NNS beverages were consumed alone without added energy or nutrients; (2) coupling interventions, where NNS beverages were consumed together with added energy and nutrients as carbohydrates; and (3) delayed coupling interventions, where NNS beverages were consumed as a preload prior to added energy and nutrients as carbohydrates. The primary outcome was a 2 h incremental area under the curve (iAUC) for blood glucose concentration. Secondary outcomes included 2 h iAUC for insulin, glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), peptide YY (PYY), ghrelin, leptin, and glucagon concentrations. Network meta-analysis and confidence in the network meta-analysis (CINeMA) were conducted in R-studio and CINeMA, respectively. Results: Thirty-six trials involving 472 predominantly healthy participants were included. Trials examined a variety of single NNS (acesulfame potassium, aspartame, cyclamate, saccharin, stevia, and sucralose) and NNS blends (acesulfame potassium + aspartame, acesulfame potassium + sucralose, acesulfame potassium + aspartame + cyclamate, and acesulfame potassium + aspartame + sucralose), along with matched water/unsweetened controls and SSBs sweetened with various caloric sugars (glucose, sucrose, and fructose). In uncoupling interventions, NNS beverages (single or blends) had no effect on postprandial glucose, insulin, GLP-1, GIP, PYY, ghrelin, and glucagon responses similar to water controls (generally, low to moderate confidence), whereas SSBs sweetened with caloric sugars (glucose and sucrose) increased postprandial glucose, insulin, GLP-1, and GIP responses with no differences in postprandial ghrelin and glucagon responses (generally, low to moderate confidence). In coupling and delayed coupling interventions, NNS beverages had no postprandial glucose and endocrine effects similar to controls (generally, low to moderate confidence). Conclusions: The available evidence suggests that NNS beverages sweetened with single or blends of NNS have no acute metabolic and endocrine effects, similar to water. These findings provide support for NNS beverages as an alternative replacement strategy for SSBs in the acute postprandial setting.

Antimicrobial resistance is one of the most pressing concerns of our time. The human diet is rich with compounds that alter bacterial gut communities and virulence-associated behaviours, suggesting food additives may be a niche for the discovery of novel anti-virulence compounds. Here, we identify three artificial sweeteners, saccharin, cyclamate and acesulfame-K (ace-K), that have a major growth inhibitory effect on priority pathogens. We further characterise the impact of ace-K on multidrug-resistant Acinetobacter baumannii, demonstrating that it can disable virulence behaviours such as biofilm formation, motility and the ability to acquire exogenous antibiotic-resistant genes. Further analysis revealed the mechanism of growth inhibition is through bulge-mediated cell lysis and that cells can be rescued by cation supplementation. Antibiotic sensitivity assays demonstrated that at sub-lethal concentrations, ace-K can resensitise A. baumannii to last resort antibiotics, including carbapenems. Using a novel ex vivo porcine skin wound model, we show that ace-K antimicrobial activity is maintained in the wound microenvironment. Our findings demonstrate the influence of artificial sweeteners on pathogen behaviour and uncover their therapeutic potential., (© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)

Artificial sweeteners (AS) were first introduced as food additives or sugar substitutes more than a century ago with the intention of supplying sweet taste without the high caloric content of sugar. AS are employed in place of sucrose (table sugar) with the view of providing sweetness to foodstuffs and bottled drinks. The end-users, along with producers of canned food and drinks, have long been captivated by the idea of replacing sugar in food items with AS. Foods that use AS in place of sugar have become increasingly common during the past decade. Artificial sugars are normally many folds sweeter than normal sugar possessing low or zero calories, which confers to their public appeal for the management of overweight issues. Due to this, they are, at present, employed by many individuals all over the world, without knowing the potential hazards associated with them. The use of AS in obese, diabetic, and/or heart patients or patients with metabolic syndrome has been approved with caution by The American Heart Association and American Diabetes Association (ADA) as a low-calorie option for normal sugar. Judicious use of sugar substitutes can help in maintaining blood glucose, calories and body weight, thus automatically minimizing the risk factors of diabetes and heart disease. Since the day of their discovery and approval, their safety issue has been quite controversial and debated extensively. The article follows an exhaustive review discussing the history, uses, and chemical features of a wide variety of sweeteners with a focus on their association with diabetes and potential adverse effects on the body., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A sensitive method followed by capillary electrophoresis with on-line perconcentration and capacitively coupled contactless conductivity detection (CE–C 4 D) was evaluated as a novel approach for the determination of three sulfanilamide artificial sweeteners (acesulfame-K, sodium saccharin and sodium cyclamate) in beverages. The on-line preconcentration technique, namely field-amplified sample injection, coupled with CE–C 4 D were successfully developed and optimized. The separation was achieved within 10 min under the following conditions: an uncoated fused-silica capillary (45 cm × 50 μm i.d., L eff = 40 cm), 20 mmol L −1 HAc as running buffer, separation voltage of −12 kV, electrokinetic injection of −11 kV × 8 s. The detection limits of acesulfame-K, sodium saccharin and sodium cyclamate were 4.4, 6.7 and 8.8 μg L −1 , respectively. The relative standard deviation varied in the range of 3.0–5.0%. Results of this study show a great potential method for the fast screening of these artificial sweeteners contents in commercial beverages. [ABSTRACT FROM AUTHOR]

In the present study, in vitro toxicity as well as biopersistence and photopersistence of four artificial sweeteners (acesulfame, cyclamate, saccharine, and sucralose) and five antibiotics (levofloxacin, lincomycin, linezolid, marbofloxacin, and sarafloxacin) and of their phototransformation products (PTPs) were investigated. Furthermore, antibiotic activity was evaluated after UV irradiation and after exposure to inocula of a sewage treatment plant. The study reveals that most of the tested compounds and their PTPs were neither readily nor inherently biodegradable in the Organisation for Economic Co-operation and Development (OECD)-biodegradability tests. The study further demonstrates that PTPs are formed upon irradiation with an Hg lamp (UV light) and, to a lesser extent, upon irradiation with a Xe lamp (mimics sunlight). Comparing the nonirradiated with the corresponding irradiated solutions, a higher chronic toxicity against bacteria was found for the irradiated solutions of linezolid. Neither cytotoxicity nor genotoxicity was found in human cervical (HeLa) and liver (Hep-G2) cells for any of the investigated compounds or their PTPs. Antimicrobial activity of the tested fluoroquinolones was reduced after UV treatment, but it was not reduced after a 28-day exposure to inocula of a sewage treatment plant. This comparative study shows that PTPs can be formed as a result of UV treatment. The study further demonstrated that UV irradiation can be effective in reducing the antimicrobial activity of antibiotics, and consequently may help to reduce antimicrobial resistance in wastewaters. Nevertheless, the study also highlights that some PTPs may exhibit a higher ecotoxicity than the respective parent compounds. Consequently, UV treatment does not transform all micropollutants into harmless compounds and may not be a large-scale effluent treatment option. [ABSTRACT FROM AUTHOR]