Synthesis, structural study and antitumor activity of novel alditol-based imidazophenanthrolines (aldo-IPs).

A series of 1H-imidazo [4,5-f][1,10] phenanthroline derivatives functionalized at 2-position with chiral, and conformationally flexible polyhydroxy alkyl chains derived from carbohydrates (alditol-based imidazophenanthrolines, aldo-IPs) is presented herein. These novel glycomimetics showed relevant and differential cytotoxic activity against several cultured tumor cell lines (PC3, HeLa and HT-29), dependent on the nature and stereochemistry of the polyhydroxy alkyl chain. The mannose-based aldo-IP demonstrated the higher cytotoxicity in the series, substantially better than cisplatin metallo-drug in all cell lines tested, and better than G-quadruplex ligand 360A in HeLa and HT29 cells. Cell cycle experiments and Annexin V-PI assays revealed that aldo-IPs induce apoptosis in HeLa cells. Initial study of DNA interactions by DNA FRET melting assays proved that the aldo-IPs produce only a slight thermal stabilization of DNA secondary structures, more pronounced in the case of quadruplex DNA. Viscosity titrations with CT dsDNA suggest that the compounds behave as DNA groove binders, whereas equilibrium dialysis assays showed that the compounds bind CT with Ka values in the range 104-105 M-1. The aldo-IP derivatives were obtained with synthetically useful yields through a feasible one-pot multistep process, by aerobic oxidative cyclization of 1,10-phenanthroline-5,6-diamine with a selection of unprotected aldoses using (NH4)2SO4 as promoter.

Foliar Application of Chelated Sugar Alcohol Calcium Improves Photosynthesis and Tuber Quality under Drought Stress in Potatoes (Solanum tuberosum L.).

Drought stress is a major threat to sustainable crop production worldwide. Despite the positive role of calcium (Ca2+) in improving plant drought tolerance in different crops, little attention has been paid to its role in mitigating drought stress in potatoes. In the present study, we studied the effect of foliar chelated sugar alcohol calcium treatments on two potato cultivars with different drought responses applied 15 and 30 days after limiting soil moisture. The results showed that the foliar application of calcium treatments alleviated the SPAD chlorophyll loss of the drought-sensitive cultivar 'Atlantic' (Atl) and reduced the inhibition of photosynthetic parameters, leaf anatomy deformation, and MDA and H2O2 content of both cultivars under drought stress. The Ca2+ treatments changed the expression of several Calcium-Dependent Protein Kinase (StCDPK) genes involved in calcium sensing and signaling and significantly increased antioxidant enzyme activities, average tuber weight per plant, and tuber quality of both cultivars. We conclude that calcium spray treatments improved the drought tolerance of both potato cultivars and were especially effective for the drought-sensitive cultivar. The present work suggests that the foliar application of calcium is a promising strategy to improve commercial potato yields and the economic efficiency of potato production under drought stress conditions.

Effects of Dietary Allitol on Body Fat Accumulation in Rats.

Allitol is a rare sugar alcohol obtained by reducing d-allulose (d-psicose). However, information on the effects of long-term dietary allitol intake is limited. This study aimed to investigate the effect of allitol supplementation, as a sugar substitute, on body fat accumulation in rats compared with sucrose, rare sugar d-allulose, or erythritol. Thirty-two male Wistar rats (3 wk old) were fed experimental diets including 5% sucrose, allitol, erythritol, or d-allulose for 8 wk ad libitum. Weight gain, food intake, and food efficiency did not differ among the groups. The total body fat mass and percentage, and intra-abdominal adipose tissue weights were significantly lower in rats fed with the allitol diet than in those fed with the sucrose diet. These body fat indicators tended to be lower in rats fed with the erythritol and d-allulose diets than in those fed with the sucrose diet, but there was no significant difference. The serum glucose-lowering effect obtained in rats fed with the d-allulose diet did not appear in rats fed with the allitol diet. These results suggest that the anti-obesity effect of allitol may be equal to or greater than that of d-allulose.

Comprehensive Assessment of Functional Effects of Commonly Used Sugar Substitute Sweeteners on Ex Vivo Human Gut Microbiome.

The composition and function of the human gut microbiome are often associated with health and disease status. Sugar substitute sweeteners are widely used food additives, although many studies using animal models have linked sweetener consumption to gut microbial changes and health issues. Whether sugar substitute sweeteners directly change the human gut microbiome functionality remains largely unknown. In this study, we systematically investigated the responses of five human gut microbiomes to 21 common sugar substitute sweeteners, using an approach combining high-throughput in vitro microbiome culturing and metaproteomic analyses to quantify functional changes in different taxa. Hierarchical clustering based on metaproteomic responses of individual microbiomes resulted in two clusters. The noncaloric artificial sweetener (NAS) cluster was composed of NASs and two sugar alcohols with shorter carbon backbones (4 or 5 carbon atoms), and the carbohydrate (CHO) cluster was composed of the remaining sugar alcohols. The metaproteomic functional responses of the CHO cluster were clustered with those of the prebiotics fructooligosaccharides and kestose. The sugar substitute sweeteners in the CHO cluster showed the ability to modulate the metabolism of Clostridia. This study provides a comprehensive evaluation of the direct effects of commonly used sugar substitute sweeteners on the functions of the human gut microbiome using a functional metaproteomic approach, improving our understanding of the roles of sugar substitute sweeteners on microbiome-associated human health and disease issues. IMPORTANCE The human gut microbiome is closely related to human health. Sugar substitute sweeteners as commonly used food additives are increasingly consumed and have potential impacts on microbiome functionality. Although many studies have evaluated the effects of a few sweeteners on gut microbiomes using animal models, the direct effect of sugar substitute sweeteners on the human gut microbiome remains largely unknown. Our results revealed that the sweetener-induced metaproteomic responses of individual microbiomes had two major patterns, which were associated with the chemical properties of the sweeteners. This study provided a comprehensive evaluation of the effects of commonly used sugar substitute sweeteners on the human gut microbiome.

Sugar alcohols have the potential as bee-safe baits for the common wasp.

BACKGROUND: Pest insects are often baited with poisoned feeding stimulants, the most common of which are sugars. However, sugars are attractive for most animal species, which makes it difficult to target only a specific pest insect species. Here, we assessed different sugar alcohols for their potential as more species-selective feeding stimulants for pest insects. RESULTS: We tested the attractiveness of the sugar alcohols sorbitol, xylitol and erythritol with a capillary feeder assay in wasps (as potential pest insects, because introduced wasps are a pest in many regions) and bees (as non-target insects). For the common wasp (Vespula vulgaris), sorbitol and xylitol acted as nutritive feeding stimulants, and erythritol acted as a non-nutritive feeding stimulant. For the buff-tailed bumble bee (Bombus terrestris), sorbitol acted as a feeding stimulant, while for the honey bee (Apis mellifera), none of the sugar alcohols acted as feeding stimulant. CONCLUSION: The species-specific preferences for sugar alcohols suggest their potential as species-selective insect baits. The wasp-specific preference for xylitol suggests its potential as a bee-safe alternative to sugar-containing bait for controlling the common wasp. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Enzymatic Synthesis of Maltitol and Its Inhibitory Effect on the Growth of Streptococcus mutans DMST 18777.

This study aimed to synthesize maltitol using recombinant CGTase from Bacillus circulans A11 with ß-cyclodextrin (ß-CD) and sorbitol as a glucosyl donor and acceptor, respectively, and assess its antibacterial activity. Optimal conditions for producing the highest yield, 25.0% (w/w), were incubation of 1% (w/v) ß-CD and sorbitol with 400 U/mL of CGTase in 20 mM phosphate buffer at pH 6.0 and 50 °C for 72 h. Subsequently, maltitol underwent large-scale production and was purified by HPLC. By mass spectrometry, the molecular weight of the synthesized maltitol was 379.08 daltons, corresponding exactly to that of standard maltitol. The relative sweetness of synthesized and standard maltitol was ~90% of that of sucrose. Spot assay on the agar plate showed that maltitol inhibited the growth of Streptococcus mutans DMST 18777 cells. In addition, the MIC and MBC values of synthesized and standard maltitol against S. mutans were also determined as 20 and 40 mg/mL, respectively. These results show that the synthesized maltitol can be produced at high yields and has the potential to be used as an anticariogenic agent in products such as toothpaste.

Antimicrobial, Cytotoxic and Mutagenic Activity of Gemini QAS Derivatives of 1,4:3,6-Dianhydro-l-iditol.

A series of quaternary diammonium salts derivatives of 1,4:3,6-dianhydro-l-iditol were synthesized, using isommanide (1,4:3,6-dianhydro-d-mannitol) as a starting material. Both aromatic (pyridine, 4-(N,N-dimethylamino)pyridine (DMAP), (3-carboxamide)pyridine; N-methylimidazole) and aliphatic (trimethylamine, N,N-dimethylhexylamine, N,N-dimethyloctylamine, N,N-dimethyldecylamine) amines were used, giving eight gemini quaternary ammonium salts (QAS). All salts were tested for their antimicrobial activity against yeasts, Candida albicans and Candida glabrata, as well as bacterial Staphylococcus aureus and Escherichia coli reference strains. Moreover, antibacterial activity against 20 isolates of S. aureus collected from patients with skin and soft tissue infections (n = 8) and strains derived from subclinical bovine mastitis milk samples (n = 12) were evaluated. Two QAS with octyl and decyl residues exhibited antimicrobial activity, whereas those with two decyl residues proved to be the most active against the tested pathogens, with MIC of 16-32, 32, and 8 µg/mL for yeast, E. coli, and S. aureus reference and clinical strains, respectively. Only QAS with decyl residues proved to be cytotoxic in MTT assay against human keratinocytes (HaCaT), IC50 12.8 ± 1.2 µg/mL. Ames test was used to assess the mutagenic potential of QAS, and none of them showed mutagenic activity in the concentration range 4-2000 µg/plate.

Astrocyte-neuron lactate transport in the ACC contributes to the occurrence of long-lasting inflammatory pain in male mice.

Lactate transport is an important means of communication between astrocytes and neurons and is implicated in a variety of neurobiological processes. However, the connection between astrocyte-neuron lactate transport and nociceptive modulation has not been well established. Here, we found that Complete Freund's adjuvant (CFA)-induced inflammation pain leads to a significant increase in extracellular lactate levels in the anterior cingulate cortex (ACC). Inhibition of glycogenolysis and lactate release in the ACC disrupted the persistent, but not acute, inflammation pain induced by CFA, and this effect was reversed by exogenous L-lactate administration. Knocking down the expression of lactate transporters (MCT1, MCT4, or MCT2) also disrupted the long lasting inflammation pain induced by CFA. Moreover, glycogenolysis in the ACC is critical for the induction of molecular changes related to neuronal plasticity, including the induction of phospho- (p-) ERK, p-CREB, and Fos. Taken together, our findings indicate that astrocyte-neuron lactate transport in the ACC is critical for the occurrence of persistent inflammation pain, suggesting a novel mechanism underlying chronic pain.

A review of antidiabetic active thiosugar sulfoniums, salacinol and neokotalanol, from plants of the genus Salacia.

During our studies characterizing functional substances from food resources for the prevention and treatment of lifestyle-related diseases, we isolated the active constituents, salacinol (1) and neokotalanol (4), and related thiosugar sulfoniums, from the roots and stems of the genus Salacia plants [Celastraceae (Hippocrateaceae)] such as Salacia reticulata Wight, S. oblonga Wall., and S. chinensis L., and observed their antidiabetic effects. These plant materials have been used traditionally in Ayurvedic medicine as a specific remedy at the early stage of diabetes, and have been extensively consumed in Japan, the United States, and other countries as a food supplement for the prevention of obesity and diabetes. Here, we review our studies on the antidiabetic effects of plants from the genus Salacia, from basic chemical and pharmacological research to their application and development as new functional food ingredients.

Noradrenaline-induced l-lactate production requires d-glucose entry and transit through the glycogen shunt in single-cultured rat astrocytes.

During cognitive efforts mediated by local neuronal networks, approximately 20% of additional energy is required; this is mediated by chemical messengers such as noradrenaline (NA). NA targets astroglial aerobic glycolysis, the hallmark of which is the end product l-lactate, a fuel for neurons. Biochemical studies have revealed that astrocytes exhibit a prominent glycogen shunt, in which a portion of d-glucose molecules entering the cytoplasm is transiently incorporated into glycogen, a buffer and source of d-glucose during increased energy demand. Here, we studied single astrocytes by measuring cytosolic L-lactate ([lac]i ) with the FRET nanosensor Laconic. We examined whether NA-induced increase in [lac]i is influenced by: (a) 2-deoxy-d-glucose (2-DG, 3 mM), a molecule that enters the cytosol and inhibits the glycolytic pathway; (b) 1,4-dideoxy-1,4-imino-d-arabinitol (DAB, 300 µM), a potent inhibitor of glycogen phosphorylase and glycogen degradation; and (c) 3-nitropropionic acid (3-NPA, 1 mM), an inhibitor of the Krebs cycle. The results of these pharmacological experiments revealed that d-glucose uptake is essential for the NA-induced increase in [lac]i , and that this exclusively arises from glycogen degradation, indicating that most, if not all, d-glucose molecules in NA-stimulated cells transit the glycogen shunt during glycolysis. Moreover, under the defined transmembrane d-glucose gradient, the glycolytic intermediates were not only used to produce l-lactate, but also to significantly support oxidative phosphorylation, as demonstrated by an elevation in [lac]i when Krebs cycle was inhibited. We conclude that l-lactate production via aerobic glycolysis is an essential energy pathway in NA-stimulated astrocytes; however, oxidative metabolism is important at rest.

Synthesis and structure-activity studies of novel anhydrohexitol-based Leucyl-tRNA synthetase inhibitors.

Leucyl-tRNA synthetase (LeuRS) is a clinically validated target for the development of antimicrobials. This enzyme catalyzes the formation of charged tRNALeu molecules, an essential substrate for protein translation. In the first step of catalysis LeuRS activates leucine using ATP, forming a leucyl-adenylate intermediate. Bi-substrate inhibitors that mimic this chemically labile phosphoanhydride-linked nucleoside have proven to be potent inhibitors of different members of the aminoacyl-tRNA synthetase family but, to date, they have demonstrated poor antibacterial activity. We synthesized a small series of 1,5-anhydrohexitol-based analogues coupled to a variety of triazoles and performed detailed structure-activity relationship studies with bacterial LeuRS. In an in vitro assay, Kiapp values in the nanomolar range were demonstrated. Inhibitory activity differences between the compounds revealed that the polarity and size of the triazole substituents affect binding. X-ray crystallographic studies of N. gonorrhoeae LeuRS in complex with all the inhibitors highlighted the crucial interactions defining their relative enzyme inhibitory activities. We further examined their in vitro antimicrobial properties by screening against several bacterial and yeast strains. While only weak antibacterial activity against M. tuberculosis was detected, the extensive structural data which were obtained could make these LeuRS inhibitors a suitable starting point towards further antibiotic development.

Elongation of the side chain by linear alkyl groups increases the potency of salacinol, a potent α-glucosidase inhibitor from the Ayurvedic traditional medicine "Salacia," against human intestinal maltase.

Four chain-extended analogs (12a-12d) and two related de-O-sulfonated analogs (13a and 13c) by introducing alkyl groups (a: R = C3H7, b R = C6H13, c: R = C8H17, d: R = C10H21) to the side chains of salacinol (1), a natural α-glucosidase inhibitor from Ayurvedic traditional medicine "Salacia", were synthesized. The α-glucosidase inhibitory activities of all the synthesized analogs were evaluated in vitro. Against human intestinal maltase, the inhibitory activities of 12a and 13a with seven-carbon side chain were equal to that of 1. In contrast, analogs (12b-12d, and 13c) exhibited higher level of inhibitory activity against the same enzyme than 1 and had equal or higher potency than those of the clinically used anti-diabetics, voglibose, acarbose, and miglitol. Thus, elongation of the side chains of 1 was effective for specifically increasing the inhibitory activity against human intestinal maltase.

Kinetic and thermodynamic insights into the inhibitory mechanism of TMG-chitotriomycin on Vibrio campbellii GH20 exo-ß-N-acetylglucosaminidase.

We investigated the inhibition kinetics of VhGlcNAcase, a GH20 exo-ß-N-acetylglucosaminidase (GlcNAcase) from the marine bacterium Vibrio campbellii (formerly V. harveyi) ATCC BAA-1116, using TMG-chitotriomycin, a natural enzyme inhibitor specific for GH20 GlcNAcases from chitin-processing organisms, with p-nitrophenyl N-acetyl-ß-d-glucosaminide (pNP-GlcNAc) as the substrate. TMG-chitotriomycin inhibited VhGlcNAcase with an IC50 of 3.0 ± 0.7 µM. Using Dixon plots, the inhibition kinetics indicated that TMG-chitotriomycin is a competitive inhibitor, with an inhibition constant Ki of 2.2 ± 0.3 µM. Isothermal titration calorimetry experiments provided the thermodynamic parameters for the binding of TMG-chitotriomycin to VhGlcNAcase and revealed that binding was driven by both favorable enthalpy and entropy changes (ΔH° = -2.5 ± 0.1 kcal/mol and -TΔS° = -5.8 ± 0.3 kcal/mol), resulting in a free energy change, ΔG°, of -8.2 ± 0.2 kcal/mol. Dissection of the entropic term showed that a favorable solvation entropy change (-TΔSsolv° = -16 ± 2 kcal/mol) is the main contributor to the entropic term.

Antibacterial Activity of Fruiting Body Extracts from Culinary-Medicinal Winter Mushroom, Flammulina velutipes (Agaricomycetes) against Oral Pathogen Streptococcus mutans.

The edible medicinal mushroom Flammulina velutipes (enokitake) has many applications as food and medicine, but its application in dentistry is unknown. This study aims to investigate the inhibitory effect of fruiting body extracts from F. velutipes on the growth and adhesion of Streptococcus mutans, the main cause of human caries, in vitro. Of the four extracts (named TG01 from water, TG02 from 95% ethanol, TG03 from 50% ethanol, and TG04 from ethyl acetate), TG03 had significant antibacterial activity (MIC = 10 mg/mL; MBC = 20 mg/mL). Planktonic growth and biofilm formation in S. mutans was repressed by TG03 at 5 mg/mL and above. Meanwhile, cytotoxicity analysis showed that TG03 was not toxic to human oral keratinocyte cells. HPLC-QQQ-MS analysis showed that the TG03 extract contained a large amount of arabitol, a sucrose substitute that reduces the development of caries. Thus, F. velutipes extracts can effectively inhibit the growth of the oral pathogen S. mutans without cytotoxicity against human oral keratinocytes. Therefore, F. velutipes is a good candidate for the development of oral hygiene agents to control dental caries.

Revisiting Bromohexitols as a Novel Class of Microenvironment-Activated Prodrugs for Cancer Therapy.

Bromohexitols represent a potent class of DNA-alkylating carbohydrate chemotherapeutics that has been largely ignored over the last decades due to safety concerns. The limited structure-activity relationship data available reveals significant changes in cytotoxicity with even subtle changes in stereochemistry. However, no attempts have been made to improve the therapeutic window by rational drug design or by using a prodrug approach to exploit differences between tumour physiology and healthy tissue, such as acidic extracellular pH and hypoxia. Herein, we report the photochemical synthesis of highly substituted endoperoxides as key precursors for dibromohexitol derivatives and investigate their use as microenvironment-activated prodrugs for targeting cancer cells. One endoperoxide was identified to have a marked increased activity under hypoxic and low pH conditions, indicating that endoperoxides may serve as microenvironment-activated prodrugs.

Anti-melanogenic activity of salacinol by inhibition of tyrosinase oligosaccharide processing.

Hyperpigmentation that manifests through melasma and solar lentigo (age spots), although mostly harmless for health, bothers many people. Controlling the rate-limiting activity of tyrosinase is most effective for suppressing excessive melanin formation and accordingly recent research has focused on the maturation of tyrosinase. Salacia, a medicinal plant, has been used to treat diabetes in India and Sri Lanka. Salacia extract reportedly contains components that inhibit the activity of α-glucosidase. Salacinol, the active ingredient in Salacia extract, has unique thiosugar sulphonium sulphate inner salt structure. Here, we observed that the salacinol component of Salacia extract possesses anti-melanogenic activity in comparison to various existing whitening agents. Although the anti-melanogenic mechanism of salacinol is presumably medicated by inhibition of tyrosinase activity, which is often found in existing whitening agents, salacinol did not inhibit tyrosinase activity in vitro. Analysis of the intracellular state of tyrosinase showed a decrease in the mature tyrosinase form due to inhibition of N-linked oligosaccharide processing. Salacinol inhibited the processing glucosidase I/II, which are involved in the initial stage of N-linked glycosylation. Owing to high activity, low cytotoxicity and high hydrophilicity, salacinol is a promising candidate compound in whitening agents aimed for external application on skin.

Natural Alternative Sweeteners and Diabetes Management.

PURPOSE OF REVIEW: The goal of this review is to discuss the data on natural alternative sweeteners and their effects on glucose homeostasis and other metabolic parameters within the past five years. We sought to answer whether common natural alternative sweeteners have a positive or negative effect on glucose control in both human and animal models, and whether the data supports their widespread use as a tool to help reduce the prevalence of diabetes and associated comorbid conditions. RECENT FINDINGS: Recent studies suggest that natural alternative sweeteners may reduce hyperglycemia, improve lipid metabolism, and have antioxidant effects particularly in those that have baseline diabetes. Diabetes and metabolic syndrome have become a global healthcare crisis and the sugar overconsumption plays a major role. The use of artificial sweeteners has become more prevalent to improve insulin resistance in those with diabetes, obesity, and metabolic syndrome, although the evidence does not support this result. There are however some promising data to suggest that natural alternative sweeteners may be a better alternative to sugar and artificial sweeteners.

Effects of probiotics and prebiotics on intestinal microbiota in mice with acute colitis based on 16S rRNA gene sequencing.

BACKGROUND: Imbalance of intestinal microbiota was closely related to colitis. Under these circumstances, regulation of enteric flora may be beneficial to the repair of inflammation. We aimed to investigate the effects of probiotics (Bifidobacterium and Lactobacillus), prebiotics and their combination on inflammation, and microflora in mice of acute colitis. METHODS: C57BL/6J mice were divided into six groups randomly (blank control group, model control group, probiotics group, synbiotics group, lactitol group and probiotics + lactitol group). Each group was given 2.5% dextran sulfate sodium drinking water for 5 days other than the blank control group. Except for the model control group, the other four groups were intervened with probiotics, synbiotics (probiotics and inulin), lactitol, and probiotics + lactitol. Mice were sacrificed after 1 week of gavage, and pathologic scores were calculated. The feces of different periods and intestinal mucosa samples were collected to analyze the differences of intestinal microbiota by 16S rRNA sequencing. Differences of two groups or multiple groups were statistically examined through unpaired Student t test and analysis of variance (ANOVA), respectively. ANOVA, Tukey, Anosim, and metastats analysis were used to compare differences of microbiota among different groups. RESULTS: After gavage for 1 week, the pathologic scores of groups with the intervention were significantly lower than those in the model control group, and the difference was statistically significant (P < 0.05). The model control group was higher in the genus of Bacteroides (relative abundance: 0.3679 vs. 0.0099, P = 0.0016) and lower in Lactobacillus (relative abundance: 0.0020 vs. 0.0122, P = 0.0188), Roseburia (relative abundance: 0.0004 vs. 0.0109, P = 0.0157), compared with the blank control group. However, the same phenomenon was not found in groups gavaged with probiotics and lactitol. Compared with model control group, mice with intervention were increased with Bifidobacterium (relative abundance: 0.0172 vs. 0.0039, P = 0.0139), Lachnospiraceae_NK4A136_group (relative abundance: 0.1139 vs. 0.0320, P = 0.0344), Lachnospiraceae_UCG-006 (relative abundance: 0.0432 vs. 0.0054, P = 0.0454), and decreased with Alistipes (relative abundance: 0.0036 vs. 0.0105, P = 0.0207) in varying degrees. The mucosal flora was more abundant than the fecal flora, and genus of Mucispirillum (relative abundance: 0.0207 vs. 0.0001, P = 0.0034) was more common in the mucosa. Lactitol group showed higher level of Akkermansia than model control group (relative abundance: 0.0138 vs. 0.0055, P = 0.0415), probiotics group (relative abundance: 0.0138 vs. 0.0022, P = 0.0041), and synbiotics group (relative abundance: 0.0138 vs. 0.0011, P = 0.0034), while probiotics + lactitol group had more abundant Akkermansia than synbiotics group (relative abundance: 0.0215 vs. 0.0013, P = 0.0315). CONCLUSIONS: Probiotics and prebiotics reduce the degree of inflammation in acute colitis mice obviously. Mice with acute colitis show reduced beneficial genera and increased harmful genera. Supplementation of probiotics and prebiotics display the advantage of increasing the proportion of helpful bacteria and regulating the balance of intestinal microbiota. Lactitol might promote the proliferation of Akkermansia.

Characterizing the selectivity of ER α-glucosidase inhibitors.

The endoplasmic reticulum (ER) contains both α-glucosidases and α-mannosidases which process the N-linked oligosaccharides of newly synthesized glycoproteins and thereby facilitate polypeptide folding and glycoprotein quality control. By acting as structural mimetics, iminosugars can selectively inhibit these ER localized α-glycosidases, preventing N-glycan trimming and providing a molecular basis for their therapeutic applications. In this study, we investigate the effects of a panel of nine iminosugars on the actions of ER luminal α-glucosidase I and α-glucosidase II. Using ER microsomes to recapitulate authentic protein N-glycosylation and oligosaccharide processing, we identify five iminosugars that selectively inhibit N-glycan trimming. Comparison of their inhibitory activities in ER microsomes against their effects on purified ER α-glucosidase II, suggests that 3,7a-diepi-alexine acts as a selective inhibitor of ER α-glucosidase I. The other active iminosugars all inhibit α-glucosidase II and, having identified 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) as the most effective of these compounds, we use in silico modeling to understand the molecular basis for this enhanced activity. Taken together, our work identifies the C-3 substituted pyrrolizidines casuarine and 3,7a-diepi-alexine as promising "second-generation" iminosugar inhibitors.

Furan formation from ingredient interactions and furan mitigation by sugar alcohols and antioxidants of bamboo leaves in milk beverage model systems.

BACKGROUND: Furan is a potential carcinogen that can be formed in various heat-treated foods, including milk beverages. Studies on the formation and mitigation of furan in milk beverages are rare. In the present study, the effects of ingredients on furan formation and the reduction of furan by sugar alcohols and antioxidants of bamboo leaves (AOB) were investigated in a milk beverage model system. RESULTS: The results obtained demonstrated that the Maillard reaction is the major pathway for furan formation in a milk beverage model system, and the type of sugar has a great influence on furan formation. High fructose corn syrup (HFCS 55) was more favorable for furan formation than sucrose. Thermal oxidation of ascorbic acid and lipids significantly enhanced furan generation. Xylitol, sorbitol and mannitol inhibited furan formation in model systems by replacing sucrose or HFCS. The maximum inhibition percentage of furan formation was observed when sucrose/HFCS was substituted completely by xylitol and the inhibition rate was 78.28% and 88.64% separately for the sucrose/HFCS-containing system. AOB significantly inhibited furan formation and the inhibition rate reached 32.13% and 28.52% separately for the sucrose/HFCS-containing system. CONCLUSION: The present study demonstrates that the use of sugar alcohols and AOB could be a feasible way of reducing furan formation in thermally processed milk beverages. © 2019 Society of Chemical Industry.