Search Results (36)

Deoxynojirimycin (DNJ), the first isolated iminosugar, is a natural alkaloid acting as a potent inhibitor of α-glucosidase with high nutritional value. It naturally occurs in plants (especially Morus spp.), microbes, and insects or can be synthesized. Diverse biological activities, such as antihyperglycemic, lipid-lowering, antitumor, antiviral, and anti-inflammatory, have been recognized for this compound. However, DNJ has not been approved as a food supplement until now. Several studies, also in clinics, are carried out on Morus spp. containing DNJ. Among Morus spp., Morus alba L. (white mulberry), Morus nigra L. (black mulberry), and Morus rubra L. (red mulberry) are the three main species that grow all over the world. Some spurious studies have been conducted on Reducose^® and Glubloc™, two products that contain DNJ and Morus alba, respectively. However, mulberry allergy, including respiratory allergy, airborne contact urticaria, anaphylaxis, oral allergy syndrome, and food induced urticaria, may be observed. This review aims to explore a crucial and timely question: how DNJ exerts its biological effects and what role it may play in therapeutic applications. We provide a comprehensive summary of the current understanding of DNJ’s pharmacological potential and the methods used for its production. We also report recent developments in clinical studies on Morus alba, Reducose^® and Glubloc™. Full article

Background/Objectives: Postprandial hyperglycemia is a risk factor for diabetes and cardiovascular diseases, even in healthy individuals. Kanzaki mulberry leaf and water chestnut tea (MW tea), a blend of mulberry (Morus alba) leaves and water chestnut (Trapa japonica) leaves and husks, is rich in polyphenols and 1-deoxynojirimycin (DNJ) and may suppress postprandial glucose spikes, but evidence regarding its short-term daily intake is limited. This study aimed to evaluate the postprandial glycemic response and safety of two-week MW tea consumption using continuous glucose monitoring (CGM). Methods: We conducted a randomized, double-blind, placebo-controlled, two-period crossover trial involving 31 participants. Each intervention period lasted two weeks, separated by a one-week washout. Participants consumed either MW tea or a placebo before meals. Interstitial glucose levels were measured every 15 min using CGM. Postprandial glucose responses were recorded every 15 min for 180 min after a standardized meal on the first day of each period. The primary outcome was the coefficient of variation (CV) in glucose levels, calculated using data from the central 10 days of each intervention period. Safety was assessed using CGM-derived hypoglycemia metrics and blood test results. Results: The CV of glucose levels during the MW tea period was significantly lower than during the placebo period (mean difference: 0.02, p = 0.0006). A significant reduction in 1 h postprandial glucose area under the curve was also observed. No significant differences were found in hypoglycemia occurrence, liver/renal/inflammatory markers, or self-reported adverse symptoms. Notably, 1,5-anhydroglucitol (1,5-AG) levels significantly increased during MW tea intake, suggesting improved glycemic control. Conclusions: Short-term consumption of Kanzaki MW tea effectively suppressed postprandial glucose variability without safety concerns. These findings support MW tea as a promising natural supplement for glycemic management and the prevention of diabetes. Full article

Iminosugars have a carbohydrate-like backbone in which the ring oxygen is replaced by nitrogen. They are naturally found in foods such as rice, buckwheat, mulberries, and fermented vegetables, and are reported to exert anti-hyperlipidemic and anti-hyperglycemic effects due to the inhibition of cellular glycosidases. This mechanism suggests their potential role in cancer treatment and prevention. In this study, two natural iminosugars, D-fagomine (FGM) and 1-deoxynojirimycin (DNJ), and their synthetic derivatives were screened for potential anticancer properties using Caco-2 and HCT-116 cells as models for the early and late stages of colon cancer, respectively. Iminosugars were found to decrease cell viability, with effects varying based on the type of iminosugar, cell type, growth condition (glucose concentration), exposure time (1 vs. 13 days), and tissue architecture (monolayer vs. spheroid). The combined use of innovative techniques, such as IncuCyte^® live cell imaging and Seahorse real-time cellular metabolic analysis, and microscopic observation after staining enabled us to detect changes in substrate utilization for energy metabolism, including increased glycolysis and alterations in lipid and glycogen stores. The evidence that iminosugars, both natural and synthetic, influence cellular bioenergetics paves the way for their potential use in various applications, including cancer treatment. Full article

Oxidative stress and inflammation are critical factors in hypertension and type 2 diabetes mellitus (T2DM). Kombucha, a fermented tea beverage, is enriched with bioactive compounds during fermentation. This study evaluated the antihypertensive, antihyperglycemic, antioxidant, and anti-inflammatory activities of kombucha made from mulberry leaf green tea (MLGT) and black tea (MLBT) during in vitro digestion. The bioaccessibility of 1-deoxynojirimycin (DNJ), γ-aminobutyric acid (GABA), phenolics, and flavonoids was assessed through simulated oral, gastric, and intestinal phases. MLGT kombucha exhibited higher initial antioxidant activity, while MLBT showed greater compound stability and ACE inhibitory activity during digestion. Notably, α-glucosidase inhibition declined significantly in the intestinal phase, in parallel with reduced DNJ and flavonoid content. Strong correlations were observed between specific phenolic acids and bioactivity profiles, highlighting ρ-coumaric and sinapic acids in ACE inhibition and DNJ in antiglycemic activity. These findings demonstrate the functional potential of mulberry leaf kombucha as a beverage to support metabolic health, pending confirmation through in vivo studies. Full article

Porcine epidemic diarrhea virus (PEDV), a highly infectious alphacoronavirus, has resulted in substantial economic losses within the global swine industry. Existing vaccines and therapeutic agents have proven inadequate in effectively preventing and controlling PEDV. Natural compounds offer distinct advantages in antiviral research due to their abundant availability, diverse biological activities, and low toxicity. In this study, the antiviral properties of the naturally occurring alkaloid 1-deoxynojirimycin (DNJ) against PEDV were examined. The CC₅₀ of DNJ was determined to be 912.5 μM through experimental analysis on Vero-E6 cells. DNJ demonstrated an inhibitory effect on PEDV activity, with a 50% inhibitory concentration (IC₅₀) of 57.76 μM. The compound primarily inhibited PEDV proliferation during the viral life cycle stages of attachment and replication. Moreover, DNJ mitigated the production of reactive oxygen species (ROS) and inflammation associated with PEDV infection. Computational docking predictions suggest that the viral non-structural proteins include Nsp12, Nsp14, and Nsp16 may serve as potential targets for DNJ. Consequently, DNJ represents a promising candidate for the development of novel therapeutic agents against PEDV. Full article

Oxidative stress (OS) is regarded as a major contributor to granulosa cellapoptosis in ovarian disease. 1-Deoxynojirimycin (1-DNJ), a naturally occurring plant alkaloid, exhibits antioxidant, anti-inflammatory, and metabolism-modulating properties. Mitochondria and endoplasmic reticulum (ER), crucial organelles regulating oxidative balance, interact through mitochondria-associated endoplasmic reticulum membranes (MAMs) for signaling and molecular exchange. However, it remains unclear whether 1-DNJ attenuates oxidative damage in ovarian granulosa cells (GCs) via MAMs-mediated ER–mitochondria crosstalk, which needs further exploration. This study aimed to investigate the mechanisms by which 1-DNJ affects oxidative damage and apoptosis induced by OS in porcine follicular GCs by regulating mitochondrial function, MAMs, and ER interactions. Here, we found that GCs suffered from OS, accompanied by the up-regulation of ROS and MDA, alongside reduced activity of antioxidant enzymes (CAT and T-SOD). Further studies revealed that the up-regulation of MAMs proteins (MFN2, MCU, and VDAC1) and pro-apoptosis proteins (BAX and Cleaved-capase3), along with increased mitochondrial ROS and Ca²⁺ levels, led to the down-regulation of MMP and ATP content. These, in turn, triggered mitochondrial dysfunction, and MAMs destabilization, and subsequent apoptosis. Additionally, the up-regulation of the protein levels of P-PERK/PERK, GRP78, ATF4, and CHOP protein expression activated the PERK-ATF4 signaling pathway, which triggered endoplasmic reticulum stress (ERS). Conversely, 1-DNJ alleviated H₂O₂-induced mitochondrial and MAMs dysfunction and ERS, which in turn attenuated apoptosis. Further, ATF4 knockdown inhibited MFN2 protein expression, which attenuated H₂O₂-induced MMP inhibition, Ca²⁺ overload, ROS production, and mitochondrial damage. In summary, 1-DNJ mitigated OS-induced mitochondrial dysfunction in GCs and regulated ER–mitochondrial communication through MAMs, reducing OS-induced apoptosis. The present study demonstrates that 1-DNJ protects ovarian GCs from OS-induced damage by modulating ER and mitochondrial homeostasis through MAMs, offering new perspectives and a theoretical basis for the treatment of ovarian diseases. Full article

The poultry industry struggles with oxidative stress affecting gut health and productivity. This study examined using 1-Deoxynojirimycin (DNJ) extracts from mulberry leaves as an antioxidant in broilers feed to combat this issue. We divided 240 broilers, aged 16 days, into six groups, including a control and groups exposed to oxidative stress through H₂O₂ injections, with different supplement levels of DNJ-E (40, 80, 120, and 160 mg/kg of the basal diet) lasting until the broilers reached 42 days old. We evaluated intestinal morphology, ultrastructure, oxidative stress markers, the tight junction, and inflammatory cytokines. Adding 40 mg/kg DNJ-E improved villus height, the villus-to-crypt ratio, and cellular ultrastructure, and increased SOD levels in the jejunum and ileum, as well as CAT levels in the duodenum and jejunum (p < 0.05), compared to the H₂O₂ group. The addition of DNJ had differential effects on oxidative stress, the intestinal barrier, and immune-related genes. Importantly, the dosages of 40 mg/kg and 80 mg/kg resulted in an upregulation of MUC2 mRNA expression (p < 0.05). These findings suggest that DNJ-E holds potential as a beneficial feed additive for enhancing broiler health, particularly at supplementation levels below 80 mg/kg, as higher concentrations may negatively influence intestinal health. Future investigations should aim to elucidate the underlying mechanisms through which DNJ-E operates within the avian gastrointestinal system. Full article

1-deoxynojirimycin (DNJ) is a well-known α-glucosidase inhibitor. A series of phenyltriazole-deoxynojirimycin hybrids containing C₄ and C₆ (4 and 6 methylenes, respectively) linkers were synthesized. These novel compounds were assessed for preliminary glucosidase inhibition and cytotoxicity tests in vitro. Among them, compounds 12–14 and 16–20 (IC₅₀: 105 ± 9–11 ± 1 μM) were more active than deoxynojirimycin (DNJ, IC₅₀ = 155 ± 15 μM). The kinetics of enzyme inhibition measured by using Lineweaver–Burk plots indicated that compounds 18 and 19 were competitive inhibitors. In addition, a molecular docking study of α-glucosidase revealed that the interaction modes and the orientations of compound 18 and DNJ were clearly different. Furthermore, in tissue culture, HL60 cell compounds showed no cytotoxicity at low concentrations. When the concentration reached 50 µM, only compound 20 exhibited cytotoxicity. The structure–activity relationships exhibit that the length of the linker and the nature of 4-position substituents on the phenyl have a significant effect on the inhibitory potency of glucosidases and cytotoxicity. Full article

Type-2 diabetes affects an increasing percentage of the world’s population and its control through dietary management, involving the consumption of health-promoting foods or their derived supplements, is a common strategy. Several mushroom species have been demonstrated to be endowed with antidiabetic properties, resulting from their ability in improving insulin sensitivity and production, or inhibiting the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase. This study aimed to investigate for the first time the hypoglycemic properties of the edible mushroom Leccinum scabrum (Bull.) Gray. Mushroom extracts were prepared through the microwave-assisted extraction (MAE) technique using green solvents with different polarity degrees. The inhibition activity of all the obtained extracts on both α-glucosidase and α-amylase was evaluated and the highest activity was observed for the EtOAc extract which showed an IC₅₀ value about 60-fold lower than the reference compound 1-deoxynojirimycin (DNJ) on α-glucosidase (0.42 ± 0.02 and 25.4 ± 0.6 µg/mL, respectively). As expected on the basis of the literature data concerning both α-glucosidase and α-amylase inhibition, a milder inhibition activity on pancreatic α-amylase was observed. Preliminary in vivo tests on Drosophila melanogaster carried out on the most active obtained extract (EtOAc) confirmed the in vitro observed hypoglycemic activity. Finally, the EtOAc extract metabolic profile was determined through GC-MS and HRMS analyses. Full article

1-Deoxynojirimycin (DNJ) is a type of alkaloid that mainly exists in mulberry fruit and leaves. DNJ inhibits α-glucosidase, reduces the absorption of sugar, and suppresses after-meal hyperglycemia. It was reported that DNJ functions in attenuating cellular oxidative stress. However, the mechanisms remain largely unknown. In this study, we firstly confirmed that 5 µmol/L DNJ treatment mitigated the oxidative DNA damage and cell senescence in human umbilical vein endothelial cells (HUVEC) cultured in medium containing 50 mmol/L glucose. Next, we found that DNJ treatment stimulates the expression of anti-oxidative response regulator, Nuclear factor (erythroid-derived 2)-like 2 (NRF2) by around 50% in cells cultured with high glucose. In addition, 8-oxoguanine DNA glycosylase (OGG1) was upregulated by over 15% after DNJ treatment to mitigate high-glucose-induced oxidative DNA damage, and it was identified as a downstream target of NRF2. Further, DNJ treatment promoted the phosphorylation and activation of AKT (ser473) by around 50% in cells cultured with high glucose, and AKT inhibitor treatment abrogated DNJ-induced upregulation of NRF2 and OGG1. Taken together, our results indicate that DNJ is an effective natural antioxidant in mitigating high-glucose-induced oxidative stress in HUVEC via activating the AKT-NRF2-OGG1 anti-oxidative response. Full article

Flavonoids and alkaloids are the major active ingredients in mulberry leaves that have outstanding medicinal value. Bacillus subtilis can effectively activate the plants defense response and regulate the plant secondary metabolism. In this study, we explored the effects of soil application of B. subtilis on the content of flavonoids and the most important alkaloids (1-deoxynojirimycin, DNJ) in mulberry leaves. Significant decreases in flavonoid content were observed in tender leaves and mature leaves after treatment with B. subtilis; at the same time, significant increases in DNJ content were observed in tender leaves. Based on widely targeted LC-MS/MS and high-throughput approaches, we screened out 904 differentially synthesized metabolites (DSMs) and 9715 differentially expressed genes (DEGs). KEGG analyses showed that these DSMs and DEGs were both significantly enriched in the biosynthesis of secondary metabolites, flavonoid synthesis and plant hormone signal transduction. Further correlation analysis of DEMs and DEGs showed that 40 key genes were involved in flavonoid biosynthesis, with 6 key genes involved in DNJ biosynthesis. The expression of CHS, CHI, F3H, F3′H, FLS, UGT and AOC significantly responded to B. subtilis soil application. This study broadens our understanding of the molecular mechanisms underlying the accumulation of flavonoids and alkaloids in mulberry leaves. Full article

Vegetables are essential for maintaining health and preventing diseases due to their nutrients and functional components. However, vegetables specifically designed for blood sugar control are limited. The mulberry tree (Morus) offers potential as a source of functional vegetables with blood-sugar-lowering properties, mainly attributed to 1-Deoxynojirimycin (DNJ). This study compared the nutritional composition and DNJ content in various edible parts of twelve mulberry tree varieties. Sensory evaluations were also conducted to assess sensory attributes. Interestingly, DNJ was found to show a positive correlation with sensory evaluations. Furthermore, the sugar content, particularly sucrose, was significantly higher in tender shoots than leaves, indicating tender shoots as a preferable choice for development as a functional food for blood sugar control. Finally, VM 19 and VM 22 are considered as good candidates for the mulberry vegetable using varieties after sensory evaluation and combining with the DNJ content. These findings provide valuable insights for future research into vegetable selections for blood sugar management and support the potential commercialization of mulberry leaf vegetables as functional food options. Full article

Mulberry leaves are a well-known traditional Chinese medicine herb, and it has been observed since ancient times that leaves collected after frost have superior medicinal properties. Therefore, understanding the changes in critical metabolic components of mulberry leaves, specifically Morus nigra L., is essential. In this study, we conducted widely targeted metabolic profiling analyses on two types of mulberry leaves, including Morus nigra L. and Morus alba L., harvested at different times. In total, we detected over 100 compounds. After frost, 51 and 58 significantly different metabolites were identified in the leaves of Morus nigra L. and Morus alba L., respectively. Further analysis revealed a significant difference in the effect of defrosting on the accumulation of metabolites in the two mulberries. Specifically, in Morus nigra L., the content of 1-deoxynojirimycin (1-DNJ) in leaves decreased after frost, while flavonoids peaked after the second frost. In Morus alba L., the content of DNJ increased after frost, reaching its peak one day after the second frost, whereas flavonoids primarily peaked one week before frost. In addition, an analysis of the influence of picking time on metabolite accumulation in two types of mulberry leaves demonstrated that leaves collected in the morning contained higher levels of DNJ alkaloids and flavonoids. These findings provide scientific guidance for determining the optimal harvesting time for mulberry leaves. Full article

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. Full article

Diabetes mellitus is a metabolic disease affecting more people every year. The treatment of diabetes and its complications involve substantial healthcare expenditures. Thus, there is a need to identify natural products that can be used as nutraceuticals to prevent and treat early-stage diabetes. White mulberry (Morus alba L.) is a plant that has been used in traditional Chinese medicine for thousands of years due to its many beneficial biological properties. White mulberry leaves are a source of 1-deoxynojirimycin (DNJ), which, due to its ability to inhibit α-glucosidase, can be used to regulate postprandial glucose concentration. In addition to consuming dried white mulberry leaves as herbal tea, many functional foods also contain this raw material. The development of the dietary supplements market brings many scientific and regulatory challenges to the safety, quality and effectiveness of such products containing concentrated amounts of nutraceuticals. In the present study, the quality of 19 products was assessed by determining the content of DNJ, selected (poly)phenols and antioxidant activity (DPPH^• assay). Nine of these products were herbal teas, and the other samples were dietary supplements. These results indicate the low quality of tested dietary supplements, the use of which (due to the low content of nutraceuticals) cannot bring the expected beneficial effects on health. Moreover, a method for determining the content of DNJ (the essential component for antidiabetic activity) based on ATR-FTIR spectroscopy combined with PLS regression has been proposed. This might be an alternative method to the commonly used chromatographic process requiring extraction and derivatization of the sample. It allows for a quick screening assessment of the quality of products containing white mulberry leaves. Full article