Trehalose

Dry eye is a common disorder in routine ophthalmological practice, and a better understanding of the complex pathophysiology is leading to improved treatment. Thealoz Duo(®) is a novel artificial tear preparation containing two active ingredients: Trehalose, a naturally occurring disaccharide with a …

Hyaluronic acid-trehalose is effective and safe, with better patient satisfaction, than existing HA-only eyedrops particularly from the first month of treatment, and offers a therapeutic advancement in the treatment of moderate to severe DED.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates a cluster of oxidative stress-inducible genes in cells. Here, we aimed to investigate whether trehalose (Tr...

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates a cluster of oxidative stress-inducible genes in cells. Here, we aimed to investigate whether trehalose (Tre) protects primary rat proximal tubular (rPT) cells against cadmium (Cd)-induced oxidative stress vi …

Developing effective theranostic nanoplex platforms for personalized disease treatment necessitates an understanding of and the ability to control live cell–nanoparticle interactions. However, aggregation of nanoparticles on the cell surface and their subsequent internalization is sparsely understood and adv

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The balance between synthesis and degradation is crucial to maintain cellular homeostasis and different mechanisms are known to keep this balance. In this review, we will provide a short overview on autophagy as an intracellular homeostatic degradative machinery. We will also describe the involvemen …

Disease modification in Parkinson's disease (PD) is an unmet medical need. In the current study, we evaluated trehalose, a safe and well-tolerated disaccharide that has previously demonstrated efficacy in rodent models of neurodegenerative diseases, including PD. In a rat model of PD, based on deliv …

Trehalose is a natural disaccharide synthesized in various life forms, but not found in vertebrates. An increasing body of evidence demonstrates exceptional bioprotective characteristics of trehalose. This review discusses the scientific findings on potential functions of trehalose in oxidative stress, protein clearance, and inflammation, with an emphasis on animal models and clinical trials in ophthalmology. The main objective is to help understand the beneficial effects of trehalose in clinical trials and practice, especially in patients suffering from ocular surface disease. The discussion is supplemented with an overview of patents for the use of trehalose in dry eye and with prospects for the 2020s.

Trehalose is a nonreducing disaccharide that has recently attracted much attention because of its ability to inhibit protein aggregation, induce autophagy, and protect against dissections and strokes. In vertebrates, the biosynthesis of trehalose was long considered absent due to the lack of annotated genes involved in this process. In contrast, trehalase (TreH), which is an enzyme required for the cleavage of trehalose, is known to be conserved and expressed. Here, we show that trehalose is present as an endogenous metabolite in the rodent hippocampus. We found that primary astrocytes were able to synthesize trehalose and release it into the extracellular space. Notably, the TreH enzyme was observed only in the soma of neurons, which are the exclusive users of this substrate. A statistical analysis of the metabolome during different stages of maturation indicated that this metabolite is implicated in neuronal maturation. A morphological analysis of primary neurons confirmed that trehalose is required for neuronal arborization.

Inappropriate protein aggregation is a key mechanism in the pathogenesis of several neurodegenerative disorders. One of the main strategies by which cells deal with abnormal protein aggregates is autophagy, a degradation pathway for intracellular aggregate-prone proteins. Trehalose, a non-reducing d …

Background Aspirin is one of the most popular NSAIDs worldwide because of its anti-inflammatory and anticoagulant effects, and however, gastrointestinal injury remains a major complication. We previously reported co-lyophilized aspirin/trehalose (Lyo A/T) decreased the aspirin-induced gastric lesions in dogs. Aim This study investigated the mechanism of gastroprotective effects of trehalose in vitro and in vivo. Methods The apoptotic assays were performed in a human gastric carcinoma cell line, which was treated with aspirin, mixed aspirin/trehalose (Mix A/T) or Lyo A/T. Gastric ulcer severity was examined after oral administration of drugs in rats. In addition, the mucosal tissue apoptotic status in drug-treated rats was evaluated. Molecular dynamics simulations and laser Raman spectroscopy were performed in order to examine the molecular properties of Lyo A/T. Results DNA fragmentation was detected in AGS cells that were treated with aspirin and Mix A/T, but not in the Lyo A/T-treated cells. There were fewer apoptotic cells in the Lyo A/T-treated cells than in the other cells. Gastric injury was reduced in rats that received oral Lyo A/T compared with the others, while PGE2 synthesis was equally decreased in all groups. TUNEL assay and immunohistochemistry of cleaved caspase-3 in the mucosal tissues also revealed that Lyo A/T treatment induced less apoptosis than the others. The Lyo A/T spectrum showed clear differences in several Raman bands compared with that of Mix A/T. Conclusions Our data showed that co-lyophilization of aspirin with trehalose reduced gastric injury, potentially through suppression of aspirin-induced mucosal cell apoptosis while retaining its anti-inflammatory effects.

It is well established that trehalose (TRH) affects the physical properties of lipid bilayers and stabilizes biological membranes. We present molecular dynamics (MD) computer simulations to investigate the interactions between lipid membranes formed by 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and TRH. Both atomistic and coarse-grained (CG) interaction models were employed, and the coarse graining of DMPC leads to a reduction in the acyl chain length corresponding to a 1,2-dilauroyl-sn-glycero-3-phosphocholine lipid (DLPC). Several modifications of the Martini interaction model, used for CG simulations, were implemented, resulting in different potentials of mean force (PMFs) for DMPC bilayer–TRH interactions. These PMFs were subsequently used in a simple two-site analytical model for the description of sugar binding at the membrane interface. In contrast to that in atomistic MD simulations, the binding in the CG model was not in agreement with the two-site model. Our interpretation is that the interaction balance, involving water, TRH, and lipids, in the CG systems needs further tuning of the force-field parameters. The area per lipid is only weakly affected by TRH concentration, whereas the compressibility modulus related to the fluctuations of the membrane increases with an increase in TRH content. In agreement with experimental findings, the bending modulus is not affected by the inclusion of TRH. The important aspects of lipid bilayer interactions with biomolecules are membrane curvature generation and sensing. In the present investigation, membrane curvature is generated by artificial buckling of the bilayer in one dimension. It turns out that TRH prefers the regions with the highest curvature, which enables the most favorable situation for lipid–sugar interactions.

This data supports the addition of trehalose to HA-containing eyedrop solutions to provide better symptomatic relief from moderate to severe DED, based on an OSDI score of

Background Trehalose is well known as a functional disaccharide with anti-metabolic activities such as suppression of adipocyte hypertrophy in mice and alleviation of impaired glucose tolerance in humans. Recently, a new type of adipocyte beige cells, involved in so-called white adipocyte tissue (WAT) browning, has received much attention as a target for adaptive thermogenesis. To clarify the relationship between adipocyte hypertrophy suppression and beige cells involved in thermogenesis, we examined the effect of trehalose on the changes in beige adipocytes in mice under normal dietary conditions. Methods Mice fed a normal diet were administered water containing 0.3% (W/V) trehalose for 16 weeks, 0.3% (W/V) maltose, or water without saccharide (controls). Body temperature and non-fasting blood glucose levels were measured every 3 weeks. After 16 weeks of these treatments, mesenteric and inguinal adipose tissues were collected for measuring adipocyte size, counting the number of UCP1 positive cells by image analysis, and preparing mRNA to analyze beige adipocyte-related gene expression. Results Mice administered a continuous intake of trehalose exhibited a thermogenic ability as represented by an increase in rectal temperature, which was maintained at a relatively high level from 3 to 9 weeks and was significantly higher at 15 weeks in comparison with that of the maltose group. In addition to the reduced hypertrophy of mesenteric and inguinal adipose tissues, the trehalose group showed a significant increase in the rates of beige adipocytes in each WAT in comparison with those of the maltose and the water groups. Interestingly, a negative correlation was found between the mean cell sizes of adipocytes and the rates of beige adipocytes in the WAT. Furthermore, real-time PCR showed that the expression of Cidea and Ucp1 mRNAs, which are markers for beige adipocytes in the inguinal adipose tissue, increased in the trehalose group. Conclusions Continuous administration of trehalose to mice fed a normal diet induced WAT browning accompanied by suppression of white adipocyte hypertrophy, elevated body temperature and decreased blood glucose levels, which resulted in enhancement of energy metabolism. Therefore, we propose trehalose as a new type of thermogenic dietary component to prevent obesity by promoting WAT browning.

Background Trehalose is a natural disaccharide that is widely distributed. A previous study has shown that daily consumption of 10 g of trehalose improves glucose tolerance in individuals with signs of metabolic syndrome. In the present study, we determined whether a lower dose (3.3 g/day) of trehalose improves glucose tolerance in healthy Japanese volunteers. Methods This was a randomized, double-blind, placebo-controlled study of healthy Japanese participants (n = 50). Each consumed 3.3 g of trehalose (n = 25) or sucrose (n = 25) daily for 78 days. Their body compositions were assessed following 0, 4, 8, and 12 weeks; and serum biochemical parameters were assayed and oral 75-g glucose tolerance tests were performed at baseline and after 12 weeks. Results There were similar changes in body composition and serum biochemistry consistent with established seasonal variations in both groups, but there were no differences in any of these parameters between the two groups. However, whereas after 12 weeks of sucrose consumption, the plasma glucose concentration 2 h after a 75-g glucose load was significantly higher than the fasting concentration, after 12 weeks of trehalose consumption the fasting and 2-h plasma glucose concentrations were similar. Furthermore, an analysis of the participants with relatively high postprandial blood glucose showed that the plasma glucose concentration 2 h after a 75-g glucose load was significantly lower in the trehalose group than in the sucrose group. Conclusions Our findings suggest that trehalose helps lower postprandial blood glucose in healthy humans with higher postprandial glucose levels within the normal range, and may therefore contribute to the prevention of pathologies that are predisposed to by postprandial hyperglycemia,, even if the daily intake of trehalose is only 3.3 g, an amount that is easily incorporated into a meal. Trial registration UMIN, UMIN000033536 . Registered 27 July 2018.

Serine protease inhibitors (serpins) family have a complex mechanism of inhibition that requires a large scale conformational change. Antithrombin (AT), a member of serpin superfamily serves as a key regulator of the blood coagulation cascade, deficiency of which leads to thrombosis. In recent years …

Accelerating the clearance of intracellular protein aggregates through elevation of autophagy represents a viable approach for the treatment of neurodegenerative diseases. In our earlier report, we have demonstrated the enhanced degradation of mutant huntingtin protein aggregates through autophagy p …

The HT-29 human adenocarcinoma cell line has been used extensively in the study of colonic cell differentiation and colon cancer. We report here that substitution of glucose with trehalose (alpha-D-glucopyranosyl-alpha-D-glucopyranoside) depresses growth and promotes mucin-producing, goblet-like mat …

This work aimed to determine the effect of homogenization pressures and addition of trehalose on the functional properties of mandarin juice enriched …

Purpose. This randomized, observer-masked, crossover study investigated the effect of two hyaluronic acid/trehalose-based containing formulations, with different physical properties, on the signs and symptoms in patients with moderate to severe dry eye disease (DED). Methods. In one group, patients received a mixture of sodium hyaluronate and trehalose (HT, Thealoz Duo®) for use during the day. In the other group, patients received a more viscous formulation consisting of hyaluronic acid, trehalose, and carbomer (HTC-gel, Thealoz Duo Gel) to use pro re nata. Both groups used HTC-gel before going to bed. Clinical standard tests for DED were performed at the beginning and end of each one-week period. Further, patient satisfaction including quality of sleep was assessed using a visual analogue scale. Results. Corneal fluorescein and conjunctival lissamine green staining scores decreased, and tear breakup time (BUT) increased for both groups ( each). Mean instillation frequency was 3.1 ± 2.6 drops/day when using HT and 1.9 ± 2.2 drops/day when using HTC-gel (). A significant improvement in the quality of sleep was observed with both treatments (). Conclusions. Our results show improvement in signs and symptoms of DED in both groups. While instillation of HTC-gel resulted in a lower instillation frequency, both formulations of trehalose showed good clinical efficacy. This trial is registered with NCT02980913.

Background: Chondroitin sulfate proteoglycans (CSPGs) are the major cause of axonal regeneration failure at the site of lesion in spinal cord injury (SCI). Inflammation is believed to stimulate the upregulation of CSPGs expression. Recent evidence showed that trehalose reduces the development of inflammation in SCI. The aim of this study was to investigate the effect of trehalose on neurocan and Neural-Glial Antigen 2 (NG2) mRNA levels in SCI in rats. Methods: In this experimental study, male rats were divided into six groups (n=15). Sham (laminectomy), SCI (laminectomy and SCI), vehicle (laminectomy and SCI, treated with phosphate buffer saline), and T10, T100 and T1000 (laminectomy and SCI, treated with 10, 100 and 1000 mM trehalose). Five rats in each group were sacrificed at 1, 3 and 7 days post-injury to measure neurocan and NG2 mRNA levels in lesion. Statistical analysis was performed using Kruskal-Wallis methods followed by the Mann-Whitney test. Results: Findings indicated that SCI upregulated neurocan and NG2 mRNA levels at all times. No significant difference was observed in neurocan and NG2 gene transcripts between SCI and vehicle groups (p>0.05). However, 10 mM trehalose downregulated the mRNA level of both neurocan (0.76 and 0.65 fold) and NG2 (0.75 and 0.70 fold) at 3 and 7 days post-SCI compared to vehicle group (p p

Trehalose (TRE), a disaccharide, is absorbed slowly and gradually increases the blood glucose (GLU) level along with reducing insulin secretion. The aim of this study was twofold. First, we examined exercise performance following ingestions of either GLU, TRE, or water (WAT). The second purpose was …

Background This pilot study was part of a larger study which compared the effect of subgingival air-polishing using trehalose powder with sonic scaling on clinical parameters during supportive periodontal therapy. Within this microbiological part of the investigation subgingival samples were taken from 10 participants to analyze the survival of different bacterial species after the two different treatments as a proof of principle. Methods In 10 participants two non-adjacent, single-root teeth requiring treatment (PD =5 mm with bleeding on probing (BOP) or > 5 mm) were selected following a split-mouth design and were treated either with a sonic scaler or air-polishing device and trehalose powder. For persistent pockets (PD =4 mm and BOP or > 4 mm), treatment was repeated after 3 months. Subgingival biofilm samples were taken at baseline (BL), subsequently and three and six months after treatment. After determination of the bacterial counts (TBL), isolated bacteria were identified by MALDI-TOF-MS. If unsuccessful, PCR and 16S rDNA sequencing were performed. Results In both treatment groups, TBL decreased immediately after treatment remaining at a lower level. This confirms the findings of the larger study regarding clinical parameters showing a comparable effect on PD, BOP and CAL. Immediately after treatment, the diversity of detected species decreased significantly more than in the sonic group (p = 0.03). After 3 months, the proportion of Gram-positive anaerobic rods was lower in the air-polishing group (powder/ sonic 7%/ 25.9%, p = 0.025). Also, there was a greater reduction of Gram-negative aerobic rods for this group at this time (air-polishing/ sonic − 0.91 / -0.23 Log10 cfu/ ml, p = 0.020). Conclusion Within the limitations of this study air-polishing and sonic treatment seem to have a comparable effect on the subgingival oral biofilm during supportive periodontal treatment. Trial registration The study was registered in an international trial register (German Clinical Trial Register number DRKS 00006296) on 10th of June 2015. HTML&TRIAL_ID = DRKS00006296.