1-deoxynojirimycin Research Articles

Enrichment of deoxynojirimycin in mulberry using cation exchange resin: Adsorption/desorption characteristics and process optimization

Deoxynojirimycin (DNJ) is an α-glucosidase inhibitor with high food values. However, the complex and costly enrichment processes have greatly prevented its application. Herein, this study aimed to propose a simple and efficient enrichment process for DNJ from Morus alba L. extracts using cation exchange resins. The LSI and D113 resins were chosen due to their excellent adsorption and desorption properties. The adsorption characteristics agreed with the pseudo-first-order kinetic model and the Langmuir isotherm model. This adsorption was chemisorption, spontaneous, endothermic and entropy-driven. Furthermore, the concentration and pH of the extracts, desorption solvent, breakthrough and elution curves, sample loading and elution rate were investigated to optimize the enrichment process by resin column chromatography. The results also showed that the purity of DNJ was improved to 44.00 % with a total recovery of 78.21 % using the LSI-D113 combination strategy. This research demonstrated the industrial feasibility of DNJ enrichment using cation exchange resins.

1-Deoxynojirimycin Mitigates Glycogen and Carbohydrate Metabolic Enzyme Alterations in High Glucose-Induced Diabetic Tilapia: Implications for Therapeutic Intervention

This study investigated the effects of 1- deoxynojirimycin (DNJ) on blood glucose levels, body weight changes, glycogen levels, and carbohydrate marker enzyme activity in a high glucose-induced experimental diabetic tilapia model. We utilized spectrophotometry assay methods to achieve this objective. DNJ treatment significantly reduced blood glucose and mitigated body weight loss compared to the diabetic control group. Furthermore, DNJ treatment increased glycogen levels in liver and muscle tissues, suggesting its potential to enhance glycogen synthesis or reduce glycogen breakdown. DNJ treatment also modulated the activity of carbohydrate marker enzymes, indicating its possible inhibitory effect on enzymes involved in carbohydrate absorption and breakdown, which in turn may improve glucose homeostasis and control. The results of this study highlight DNJ's potential as a therapeutic agent for diseases associated with glycogen metabolism and glucose homeostasis, as well as its ability to influence body weight changes in diabetic conditions. Our findings contribute to the growing body of research on DNJ as a potential therapeutic agent for illnesses linked to glycogen and underscore its therapeutic potential for future treatments targeting glucose metabolism, glycemic control, and weight management.

Exploring the Potential of Iminosugars as Antivirals for Crimean-Congo Haemorrhagic Fever Virus, Using the Surrogate Hazara Virus: Liquid-Chromatography-Based Mapping of Viral N-Glycosylation and In Vitro Antiviral Assays.

Crimean-Congo haemorrhagic fever virus (CCHFV) is a pathogen of increasing public health concern, being a widely distributed arbovirus and the causative agent of the potentially fatal Crimean-Congo haemorrhagic fever. Hazara virus (HAZV) is a genetically and serologically related virus that has been proposed as a surrogate for antiviral and vaccine testing for CCHFV. Glycosylation analysis of HAZV has been limited; first, we confirmed for the first time the occupation of two N-glycosylation sites in the HAZV glycoprotein. Despite this, there was no apparent antiviral efficacy of a panel of iminosugars against HAZV, as determined by quantification of the total secretion and infectious virus titres produced following infection of SW13 and Vero cells. This lack of efficacy was not due to an inability of deoxynojirimycin (DNJ)-derivative iminosugars to access and inhibit endoplasmic reticulum α-glucosidases, as demonstrated by free oligosaccharide analysis in uninfected and infected SW13 and uninfected Vero cells. Even so, iminosugars may yet have potential as antivirals for CCHFV since the positions and importance of N-linked glycans may differ between the viruses, a hypothesis requiring further evaluation.

Xanthone sulfonamide derivatives-A novel series of α-glucosidase inhibitors with different inhibitory types

In order to discover highly potent α-glucosidase inhibitors, 20 xanthone-benzenesulfonamide derivatives were designed and synthesized. As expected, most of these derivatives exhibited good to excellent inhibitory activities, the IC50 values of these xanthone sulfonamides varied from 0.4 ± 0.05 to 52.2 ± 2.1 µM. Especially, compound 4ag showed the most potent activity (IC50 = 0.4 µM, with 111-fold more potent than the positive control 1- deoxynojirimycin (DNJ), which is a leap compared to our previous xanthone compound. It was noteworthy that these derivatives can be competitive, noncompetitive or uncompetitive inhibitors, while these inhibitory types differed by the alteration of the substituents on the benzene ring of benzenesulfonamide. To give insight into this interesting effect, further docking study was performed, indicating the flexible conformations introduced by the sulfonamide structure affect the binding site and binding mode of these compounds with the enzyme. Furthermore the uncompetitive inhibitors showed significantly stronger binding interactions with the enzyme-substrate complex than the enzyme. Additionally, the competitive inhibitor 4aj (1 µM) exhibited a similar glucose-level decreasing and glucose up-take increasing effect compared to DNJ (5 µM), the positive control in HepG2 cells at five-fold lower concentration, revealing that this compound has promising hypoglycemic effect at the cellular level.

Antiviral effects of deoxynojirimycin (DNJ)-based iminosugars in dengue virus-infected primary dendritic cells

Dendritic cells (DCs) are important targets for dengue virus (DENV) infection and play a significant role in the early immune response. Antiviral effects of iminosugars against DENV in primary cells have been demonstrated previously in monocyte-derived macrophages (MDMΦs). Given the important role played by DCs in innate immune defense against DENV, the antiviral effects of three deoxynojirimycin (DNJ) derivatives (NN-DNJ, EOO-DNJ and 2THO-DNJ) and a deoxygalactonojirimycin (DGJ) negative control were evaluated in DENV-infected primary human monocyte-derived immature DCs (imDCs). DNJ- but not DGJ-derivatives elicited antiviral activity in DENV-infected imDCs, similar to that observed in MDMΦs. The DNJ-derivatives inhibited DENV secretion in a dose-dependent manner. Endoplasmic reticulum (ER) α-glucosidase I inhibition by DNJ-derived iminosugars, at concentrations of 3.16 μM, correlated with a reduction in the specific infectivity of virions that were still secreted, as well as a reduction in DENV-induced tumour necrosis factor alpha secretion. This suggests iminosugar-mediated ER α-glucosidase I inhibition may give rise to further benefits during DENV infection, beyond the reduction in viral secretion associated with ER α-glucosidase II inhibition.

Hybrid Multivalent Jack Bean α-Mannosidase Inhibitors: The First Example of Gold Nanoparticles Decorated with Deoxynojirimycin Inhitopes.

Among carbohydrate-processing enzymes, Jack bean α-mannosidase (JBα-man) is the glycosidase with the best responsiveness to the multivalent presentation of iminosugar inhitopes. We report, in this work, the preparation of water dispersible gold nanoparticles simultaneously coated with the iminosugar deoxynojirimycin (DNJ) inhitope and simple monosaccharides (β-d-gluco- or α-d-mannosides). The display of DNJ at the gold surface has been modulated (i) by using an amphiphilic linker longer than the aliphatic chain used for the monosaccharides and (ii) by presenting the inhitope, not only in monomeric form, but also in a trimeric fashion through combination of a dendron approach with glyconanotechnology. The latter strategy resulted in a strong enhancement of the inhibitory activity towards JBα-man, with a Ki in the nanomolar range (Ki = 84 nM), i.e., more than three orders of magnitude higher than the monovalent reference compound.

Mulberry leaf attenuates atherosclerotic lesions in patients with coronary heart disease possibly via 1-Deoxynojirimycin: A placebo-controlled, double-blind clinical trial.

Mulberry leaf tea reduces atherosclerotic lesions and its main component is Deoxynojirimycin (DNJ). We aimed to explore the effects of Mulberry leaf DNJ (MLD) on atherosclerotic lesions in the patients with coronary heart disease (CHD). MLD and serum DNJ was detected by high-performance liquid chromatography (HPLC). The CHD patients with low-density lipoprotein cholesterol>140mg/dl were assigned into the EG (MLD treatment) and the CG (placebo treatment) groups. Serum biochemical indices, the cerebrovascular and cardiovascular events and carotid intima-media thickness (IMT) were measured before and after a 1-year intervention. Pearson Correlation Coefficient test was used to explore the relationship between serum levels of DNJ and IMT values. Serum DNJ was 70±50ng/ml in the EG group but no serum DNJ was detected in the CG group. The incidence of cerebrovascular and cardiovascular events in the EG was lower than that in the CG group (p<.05). MLD therapy improved antioxidant and anti-inflammatory properties and serum lipid profile (p<.05). The IMT values in the EG group were lower than those in the CG group (p<.05). Serum levels of DNJ had a strong negative relationship with IMT values. MLD treatment attenuates atherosclerotic lesions possibly via DNJ. PRACTICAL APPLICATIONS: Mulberry leaves Deoxynojirimycin (MLD) treatment improved antioxidant and anti-inflammatory properties and serum lipid profile in heart disease patients. MLD reduce carotid intima-media thickness (IMT) and serum levels of DNJ (the main ingredient of mulberry leaf) had a strong relationship with IMT values. MLD is an amazing treat used for reducing the incidence of cerebrovascular and cardiovascular events in heart disease patients.

Synthesis and Glycosidase Inhibition Properties of Calix[8]arene-Based Iminosugar Click Clusters

A set of 6- to 24-valent clusters was constructed with terminal deoxynojirimycin (DNJ) inhibitory heads through C6 or C9 linkers by way of Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions between mono- or trivalent azido-armed iminosugars and calix[8]arene scaffolds differing in their valency and their rigidity but not in their size. The power of multivalency to upgrade the inhibition potency of the weak DNJ inhibitor (monovalent DNJ Ki being at 322 and 188 µM for C6 or C9 linkers, respectively) was evaluated on the model glycosidase Jack Bean α-mannosidase (JBα-man). Although for the clusters with the shorter C6 linker the rigidity of the scaffold was essential, these parameters had no influence for clusters with C9 chains: all of them showed rather good relative affinity enhancements per inhibitory epitopes between 70 and 160 highlighting the sound combination of the calix[8]arene core and the long alkyl arms. Preliminary docking studies were performed to get insights into the preferred binding modes.

Study on the Synthesis and Biological Activities of N-Alkylated Deoxynojirimycin Derivatives with a Terminal Tertiary Amine

A series of N-alkylated deoxynojirimycin (DNJ) derivatives connected to a terminal tertiary amine at the alkyl chains of various lengths were prepared. These novel synthetic compounds were assessed for preliminary glucosidase inhibition and anticancer activities in vitro. Potent and selective inhibition was observed among them. Compound 7d (IC50 = 0.052 mM) showed improved and selective inhibitory activity against ?-glucosidase compared to DNJ (IC50 = 0.65 mM). In addition, analysis of the kinetics of enzyme inhibition by using Lineweaver-Burk plots indicated that 7d inhibited ?-glu-cosidase in a competitive manner, suggesting that 7d was expected to bind to the active site of ?-glucosidase. Compounds 8b and 8c were found to be moderate and selective inhibitors of ?-glucosidase. Nevertheless, none of compounds inhib-ited the growth of B16F10 melanoma cells.

Strategy for Designing Selective Lysosomal Acid α-Glucosidase Inhibitors: Binding Orientation and Influence on Selectivity.

Deoxynojirimycin (DNJ) is the archetypal iminosugar, in which the configuration of the hydroxyl groups in the piperidine ring truly mimic those of d-glucopyranose; DNJ and derivatives have beneficial effects as therapeutic agents, such as anti-diabetic and antiviral agents, and pharmacological chaperones for genetic disorders, because they have been shown to inhibit α-glucosidases from various sources. However, attempts to design a better molecule based solely on structural similarity cannot produce selectivity between α-glucosidases that are localized in multiple organs and tissues, because the differences of each sugar-recognition site are very subtle. In this study, we provide the first example of a design strategy for selective lysosomal acid α-glucosidase (GAA) inhibitors focusing on the alkyl chain storage site. Our design of α-1-C-heptyl-1,4-dideoxy-1,4-imino-l-arabinitol (LAB) produced a potent inhibitor of the GAA, with an IC50 value of 0.44 µM. It displayed a remarkable selectivity toward GAA (selectivity index value of 168.2). A molecular dynamic simulation study revealed that the ligand-binding conformation stability gradually improved with increasing length of the α-1-C-alkyl chain. It is noteworthy that α-1-C-heptyl-LAB formed clearly different interactions from DNJ and had favored hydrophobic interactions with Trp481, Phe525, and Met519 at the alkyl chain storage pocket of GAA. Moreover, a molecular docking study revealed that endoplasmic reticulum (ER) α-glucosidase II does not have enough space to accommodate these alkyl chains. Therefore, the design strategy focusing on the shape and acceptability of long alkyl chain at each α-glucosidase may lead to the creation of more selective and practically useful inhibitors.

Iminosugars With Endoplasmic Reticulum α-Glucosidase Inhibitor Activity Inhibit ZIKV Replication and Reverse Cytopathogenicity in vitro.

Zika virus (ZIKV), a vector-borne virus of the family Flaviviridae, continues to spread and remains a significant global public health threat. Currently, there are no approved vaccines or antivirals against ZIKV. We investigated the anti-ZIKV ability of three iminosugars with endoplasmic reticulum α-glucosidase inhibitor (ER-AGI) activity, namely deoxynojirimycin (DNJ), castanospermine, and celgosivir. None of the three iminosugars showed any significant cytotoxicity in Vero or human microglia CHME3 cells when applied for 72 h at concentrations up to 100 μM. Iminosugar treatment of Vero or CHME3 cells prior to ZIKV infection resulted in significant inhibition of ZIKV replication over 48 h. Reduction in ZIKV replication in iminosugar-treated cells was not associated with any significant change in the expression levels of key antiviral genes. Following infection with three different strains of ZIKV, iminosugar-treated Vero or CHME3 cells showed no cell death, whereas vehicle-treated control cells exhibited 50–60% cell death at 72 h post-infection (hpi). While there was no significant difference in apoptosis between iminosugar-treated and control cells, iminosugar-treated cells exhibited a substantial reduction of necrosis at 72 hpi following ZIKV infection. In summary, iminosugars with ER-AGI activity inhibit ZIKV replication and significantly reduce necrosis without altering the antiviral gene expression and apoptosis of infected human cells. The results of this study strongly suggest that iminosugars are promising anti-ZIKV antiviral agents and such warrant further in vivo studies.

Iminosugars: Effects of Stereochemistry, Ring Size, and N-Substituents on Glucosidase Activities.

N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus. Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs. Thus, a small library of iminosugars (14 compounds) displaying different stereochemistry, ring size, and N-substitutions was successfully synthesized from a common precursor, D-mannitol, by utilizing an SN2 aminocyclization reaction via two isomeric bis-epoxides. The evaluation of the prospective inhibitors on glucosidases revealed that merely D-gluco-piperidine (miglitol, 41a) and L-ido-azepane (41b) DNJ-derivatives bearing the N-hydroxylethyl group showed inhibition towards α-glucosidase with IC50 41 µM and 138 µM, respectively, using DNJ as reference (IC50 134 µM). On the other hand, β-glucosidase inhibition was achieved for glucose-inverted configuration (C-2 and C-5) derivatives, as novel L-gulo-piperidine (27a) and D-manno-azepane (27b), preserving the N-butyl chain, with IC50 109 and 184 µM, respectively, comparable to miglustat with the same N-butyl substituent (40a, IC50 172 µM). Interestingly, the seven-membered ring L-ido-azepane (40b) displayed near twice the activity (IC50 80 µM) of the corresponding D-gluco-piperidine miglustat drug (40a). Furthermore, besides α-glucosidase inhibition, both miglitol (41a) and L-ido-azepane (41b) proved to be the strongest β-glucosidase inhibitors of the series with IC50 of 4 µM.

Coating rice with mulberry leaves rich in deoxynojirimycin ameliorates hyperglycemia and dyslipidemia in C57BL/KsJ db/db mice.

BACKGROUND/OBJECTIVESMulberry leaf (ML) has been shown to have an inhibitory effect on α-glucosidase, and suppresses postprandial hyperglycemia, which may be related to its deoxynojirimycin (DNJ) content. This study was conducted to investigate the hypoglycemic and dyslipidemic effects of rice coated with ML rich in DNJ in a type 2 diabetes mouse model.MATERIALS/METHODSThe mice were divided into four groups (n = 8 each): non-diabetic normal control (NC); diabetic control (DM-C), fed with 10% polished rice powder (DM-R); and fed with 10% polished rice powder coated with DNJ-rich ML (DM-DNJR).RESULTSSupplementation with DNJR for six weeks decreased levels of fasting blood glucose, plasma insulin, triglyceride, total cholesterol, and blood glycosylated hemoglobin; conversely, levels of glucagon-like peptide-1 and high-density lipoprotein-cholesterol showed an increase in the same treatment. In addition, weights of mesenteric, epididymal, and total adipose tissues decreased with DNJR supplementation, when compared with diabetic control db/db mice, while maltase, lactase, and sucrase activity in the small intestine were inhibited. The anti-diabetic effects were marginally greater in the DM-DNJR group than in the DM-R group.CONCLUSIONSThese results suggest that rice coated with ML rich in DNJ can reduce hyperglycemia and hyperlipidemia in db/db mice, and may prove useful for individuals with diabetes.

Synthesis and characterization of novel, conjugated, fluorescent DNJ derivatives for α-glucosidase recognition

A series of five new fluorescent deoxynojirimycin (DNJ) conjugates were synthesized and evaluated for their inhibitory effect (IC50) on several α- and β-glucosidases. Three of the conjugates showed enhanced activity. The two synthetic conjugates, DNJ-CF31 and DNJ-Me 2, exhibited improved α-glucosidase inhibitory effects compared to DNJ and miglitol. Interestingly, conjugates 1 and 2 showed strong inhibition of almond-derived β-glucosidase, in contrast to the inhibition tendencies of other inhibitors. Conjugate 5 strongly inhibited rat intestinal maltase, even at 0.10μM. A docking study indicated that all five conjugates bind to the active site of α-glucosidase (PDB: 3L4V, derived from Homo sapiens). The DNJ portion of the conjugate fits into the cavity of the enzyme, and the fluorescent part locates randomly on the outside surface. Thus, it is likely that these conjugates can specifically recognize intestinal cells, specifically the α-glucosidase on cell membranes.

Total synthesis of N-butyl-1-deoxynojirimycin

GRAPHICAL ABSTRACT

Evaluation of monovalent and multivalent iminosugars to modulate Candida albicans β-1,2-mannosyltransferase activities

β-1,2-Linked oligomannosides substitute the cell wall of numerous yeast species. Several of those including Candida albicans may cause severe infections associated with high rates of morbidity and mortality, especially in immunocompromised patients. β-1,2-Mannosides are known to be involved in the pathogenic process and to elicit an immune response from the host. In C. albicans, the synthesis of β-mannosides is under the control of a family of nine genes coding for putative β-mannosyltransferases. Two of them, CaBmt1 and CaBmt3, have been shown to initiate and prime the elongation of the β-mannosides on the cell-wall mannan core. In the present study, we have assessed the modulating activities of monovalent and multivalent iminosugar analogs on these enzymes in order to control the enzymatic bio-synthesis of β-mannosides. We have identified a monovalent deoxynojirimycin (DNJ) derivative that inhibits the CaBmt1-catalyzed initiating activity, and mono-, tetra- and polyvalent deoxymannojirimycin (DMJ) that modulate the CaBmt1 activity toward the formation of a single major product. Analysis of the aggregating properties of the multivalent iminosugars showed their ability to elicit clusterization of both CaBmt1 and CaBmt3, without affecting their activity. These results suggest promising roles for multivalent iminosugars as controlling agents for the biosynthesis of β-1,2 mannosides and for monovalent DNJ derivative as a first target for the design of future β-mannosyltransferase inhibitors.

Study of the Aminoglycoside Subsistence Phenotype of Bacteria Residing in the Gut of Humans and Zoo Animals.

Recent studies indicate that next to antibiotic resistance, bacteria are able to subsist on antibiotics as a carbon source. Here we evaluated the potential of gut bacteria from healthy human volunteers and zoo animals to subsist on antibiotics. Nine gut isolates of Escherichia coli and Cellulosimicrobium sp. displayed increases in colony forming units (CFU) during incubations in minimal medium with only antibiotics added, i.e., the antibiotic subsistence phenotype. Furthermore, laboratory strains of E. coli and Pseudomonas putida equipped with the aminoglycoside 3′ phosphotransferase II gene also displayed the subsistence phenotype on aminoglycosides. In order to address which endogenous genes could be involved in these subsistence phenotypes, the broad-range glycosyl-hydrolase inhibiting iminosugar deoxynojirimycin (DNJ) was used. Addition of DNJ to minimal medium containing glucose showed initial growth retardation of resistant E. coli, which was rapidly recovered to normal growth. In contrast, addition of DNJ to minimal medium containing kanamycin arrested resistant E. coli growth, suggesting that glycosyl-hydrolases were involved in the subsistence phenotype. However, antibiotic degradation experiments showed no reduction in kanamycin, even though the number of CFUs increased. Although antibiotic subsistence phenotypes are readily observed in bacterial species, and are even found in susceptible laboratory strains carrying standard resistance genes, we conclude there is a discrepancy between the observed antibiotic subsistence phenotype and actual antibiotic degradation. Based on these results we can hypothesize that aminoglycoside modifying enzymes might first inactivate the antibiotic (i.e., by acetylation of amino groups, modification of hydroxyl groups by adenylation and phosphorylation respectively), before the subsequent action of catabolic enzymes. Even though we do not dispute that antibiotics could be used as a single carbon source, our observations show that antibiotic subsistence should be carefully examined with precise degradation studies, and that its mechanistic basis remains inconclusive.

An Improved Synthetic Method for N-Butyl-1-Deoxynojirimycin

N-butyl-1-deoxynojirimycin (NB-DNJ) based on imino sugars Deoxynojirimycin (DNJ) has been approved for treatment of Gaucher’s disease. Here, an improved synthetic procedureof NB-DNJ was described. High yields can be achieved during the introduction steps of n-butyl by combining a strong nucleophilicity of imine in the iminosugar andan easy leaving group methanesulfonatein butyl, which is much higher than the similar reported procedures. This method can be served as an excellent solution to the synthesis of various N-alkyl substituted chain DNJ, even applied to large-scale production.

Efficiency of Egyptian mulberry water extracts in controlling nephropathy complications in diabetic rats

The aim of the present study was to determine the amount and antifree radical activity of Deoxynojirimycin (DNJ) in Egyptian white and black mulberry fruits and leaves water extracts. Moreover, the study aimed to evaluate the water extracts effect of Egyptian white and black mulberry fruits and leaves, on improving hyperglycemic condition and renal complications in diabetic rats. Seventy-two adult male albino rats Sprague-Dawley strain were equally divided into six groups: group (1) healthy control and group (2) diabetic control were given tap water by gavage tube, groups (3-6) diabetic treated with different water extracts of mulberry white fruits (WMFWE), white leaves (WMLWE), black fruits (BMFWE) and black leaves (BMLWE) (containing 50mg DNJ/kg body weight) by gavages' tube daily for 28 days. At the end of the experiment, rats were sacrificed under ether anesthesia. Blood samples were collected to separate serum; also kidneys were removed for biochemical parameters estimation. The High Performance Liquid Chromatography (HPLC) analysis of the mulberry extracts showed that water extracts contained higher amount of DNJ than methanol or ethanol extracts. Also mulberry leaves had higher amount of DNJ than fruits and the amount of DNJ in black mulberry was more than the white one. The treatment with mulberry water extracts effectively decreased the blood glucose level, glycated hemoglobin percentage, renal aldose reductase activity and renal protein level as compared to untreated diabetic control rats; on the other hand there was an elevation of insulin level. Also mulberry extracts ameliorate the oxidative stress status with significant elevation in nonenzymatic antioxidant with significant improvement in kidney function parameters. Based on the presented data in this study, it can be concluded that mulberry extracts possess antidiabetic effect and improving properties of nephropathy complications.

Inhibition of α-glucosidase activity by N-deoxynojirimycin analogs in several insect phloem sap feeders.

Secondary metabolites and synthetic iminosugars that structurally resemble monosaccharides are potent inhibitors of α-glucosidase activity. The enzyme is core in cleaving sucrose in phloem feeding insects and it also plays a crucial role of reducing osmotic stress via the formation of oligosaccharides. Inhibition of hydrolysis by iminosugars should result in nutritional deficiencies and/or disruption of normal osmoregulation. Deoxynojirimycin (DNJ) and 2 N-alkylated analogs [N-butyl DNJ (NB-DNJ) and N-nonyl DNJ (NN-DNJ)] were the major iminosugars used throughout the study. The extensive experiments conducted with α-glucosidase of the whitefly Bemisia tabaci indicated the competitive nature of inhibition and that the hydrophilic DNJ is a potent inhibitor in comparison to the more hydrophobic NB-DNJ and NN-DNJ compounds. The same inhibitory pattern was observed with the psyllid Cacopsylla bidens α-glucosidase. In contrast to the above pattern, enzymes of the aphids, Myzus persicae and Aphis gossypii were more sensitive to the hydrophobic iminosugars as compared to DNJ. In vivo experiments in which adult B. tabaci were fed dietary iminosugars, show that the hydrophilic DNJ was far less toxic than the lipophilic NB-DNJ and NN-DNJ. It is proposed that this pattern is attributed to the better accessibility of the hydrophobic NN-DNJ to the α-glucosidase membrane-bound compartment in the midgut. Based on the inhibitory effects of certain polyhydroxy N-alkylated iminosugars, α-glucosidase of phloem feeding hemipterans could serve as an attractive target site for developing novel pest control agents.