Search Results (58)

N-Alkyl deoxynojirimycin-derived drugs, belonging to the class of iminosugars, are well-known for their α-glucosidase inhibitory activity. N-Butyl-deoxynojirimycin (N-butyl-DNJ; NB-DNJ; also known as miglustat or UV-1) has been developed for the treatment of type 1 Gaucher disease and Niemann–Pick disease type C as Zavesca^®. Furthermore, it behaves as a host-targeted glucomimetic that inhibits endoplasmic reticulum α-glucosidase I and II (GluI and GluII, respectively) enzymes, resulting in improper glycosylation and misfolding of viral glycoproteins; thus, it is a potential antiviral agent. It is studied against a broad range of viruses in vitro and in vivo; however, its utility as antiviral has not been fully explored. Other N-alkylated congeners of DNJ are in preclinical and clinical studies for diverse viral infections. The iminosugar N-9′-methoxynonyl-1-deoxynojirimycin (MON-DNJ or UV-4) is probably the most studied and potent inhibitor of α-Glu I and α-Glu II in clinical trials. It is often studied in the form of its hydrochloride salt (UV-4B) and has broad-spectrum activity against diverse viruses, including dengue and influenza. In clinical trials, it was found to be safe at all doses tested up to 1000 mg. In this paper, an overview on N-alkyl derivatives of DNJ is reported, focusing on their antiviral activity. The literature search was carried out by means of three literature databases, i.e., PubMed/MEDLINE, Google Scholar, and Scopus, screened using different keywords. A brief history of the discovery of their usefulness as antivirals is given, as well as the most recent studies on new compounds belonging to this class. Since different names are often used for the same compound, we tried to dissipate confusion and bring some order to this jumble of names. Specifically, in the tables, all the diverse names used to identify each compound, were reported. Full article

Background: This study aimed to explore the synergistic hypoglycemic effect and mechanism of 1-deoxynojirimycin (DNJ) in mulberry leaves and theaflavins (TFs) in black tea. Methods: The synergistic inhibition of α-glucosidase and α-amylase by DNJ-TFs was evaluated using enzyme assays and the Chou–Talalay model. Insulin-resistant (IR) HepG2 cells and high-fat diet (HFD)-induced type 2 diabetes mellitus mice were treated with DNJ, TFs, or DNJ-TFs, determining the efficacy of drug combinations by measuring glycolipids and inflammatory factors. Network pharmacology and molecular docking were used to identify key target genes and signaling pathways, and CETSA experiments were used to verify the binding of drugs to targets. Key genes were further verified by immunofluorescence, Western blot, and Real-time PCR. Results: DNJ-TFs synergistically suppressed α-glucosidase (CI = 0.85) and α-amylase (CI = 0.76). In HepG2 cells, DNJ-TFs ameliorated palmitic acid-induced IR by promoting glucose uptake, attenuating lipid accumulation, and regulating glycolipid metabolism. In HFD mice, DNJ-TFs counteracted hyperglycemia, dyslipidemia, systemic inflammation and oxidative stress, elevated HOMA-IR, and hepatic steatosis. Network pharmacology integrated with experimental validation identified PTGS2 and MMP9 as key binding targets of DNJ and TFs. Furthermore, DNJ-TFs could inhibit the increase in liver TNFα protein and the decrease in p-AKT, p-GSKα, p-GSKβ, and GLUT2 protein caused by high fat, both in vivo and in vitro. Conclusions: DNJ and TFs exert synergistic glucose-lowering effects by targeting PTGS2/MMP9 and regulating the TNFα/AKT/GSK3/GLUT2 axis, providing a promising natural therapeutic strategy for diabetes management. Full article

This study aimed to establish an integrated variety–technology cultivation pathway for the new forage mulberry variety ‘Fengyuan No. 1’, linking salt tolerance mechanisms with practical application. A systematic investigation was conducted via a pot experiment with a 0–5‰ NaCl gradient and a field trial comparing three cultivation modes: Ridge Planting (RP), Furrow Planting (FP), and Flat-Bed Planting (FBP). Key findings are as follows. (1) The salt tolerance threshold was clearly defined: a 100% survival rate at salinity ≤ 4‰ (with no injury symptoms at ≤3‰), and 5‰ identified as the lethal threshold (33.33% survival). Salt stress triggered a resource reallocation strategy, increasing the leaf-to-stem fresh weight ratio from 1.53 (0‰) to 2.78 (5‰) to prioritize leaf photosynthetic function. Stable leaf circularity (0.83–0.87) indicated morphological stress resistance. (2) Optimized cultivation pathways were identified: FBP was the core pathway for maximizing biomass accumulation (root, stem, and leaf fresh weights were 5.0, 2.3, and 1.5 times those of RP, respectively) and resulted in the lowest leaf Na⁺ accumulation (124 mg/kg), making it suitable for lightly to moderately saline–alkali land (≤4‰). FP served as an effective pathway for salt avoidance and height promotion (plant height: 113.18 cm). RP constituted a specialized pathway for high-quality forage, yielding the highest crude protein content (23.3 g/100 g). (3) Cultivation modes significantly affected functional components; FBP activated alkaloid DNJ synthesis (215.16 mg/kg), whereas RP and FP increased osmolyte GABA accumulation (~586 mg/kg). In conclusion, this study integrates a complete technical pathway from salt tolerance mechanism analysis to diversified cultivation options, providing a systematic variety–technology solution for the industrial development of forage mulberry on coastal saline–alkali land. Full article

Glucosidase II (GluII) is a heterodimeric enzyme localized in the endoplasmic reticulum (ER), essential for the sequential trimming of glucose residues during N-linked glycosylation. This critical function facilitates glycoprotein folding via the calnexin/calreticulin chaperone system, maintaining ER homeostasis. Dysregulation or inhibition of GluII has been implicated in various pathological processes, including cancer, viral infections, and glycoprotein misfolding disorders. This review summarizes the current knowledge of GluII’s structure and function, highlights a wide range of natural and synthetic GluII inhibitors—including iminosugar derivatives (e.g., deoxynojirimycin (DNJ), castanospermine (CAST)), non-iminosugar compounds (e.g., bromoconduritol, catechins), and mechanism-based cyclophellitol analogues—and evaluates their biological effects and therapeutic potential. The cellular impact of GluII inhibition is explored in the context of ER stress, unfolded protein response (UPR), tumor cell apoptosis, and viral replication. Key challenges in developing selective GluII inhibitors are discussed, with a focus on strategies to minimize off-target effects, including prodrug design, allosteric modulation, and emerging genetic approaches such as microRNA (miRNA)-mediated downregulation of GluII subunits. Taken together, these insights underscore the therapeutic relevance of GluII as a druggable target and pave the way for the rational design of next-generation inhibitors in oncology, infectious diseases, and metabolic disorders. Full article

This study investigated the effects of Bacillus subtilis (B. subtilis) supplementation on microbiota and metabolites in the feces of Leizhou goats. Eight Leizhou goats were used in a replicated 4 × 4 Latin square design according to their gender (nanny goats and billy goats) with a 4 × 2 factorial arrangement of treatments that included four B. subtilis additive doses (control [0 g/d; NC, BC], low [2.5 g/d, NL, BL], medium [5 g/d, NM, BM], and high [7.5 g/d, NH, BH]) and 28 d periods (n = 4 per group), each consisting of 27 d adaption and 1 d sample collection. After collecting 32 fecal samples, 16S rRNA gene sequencing and LC-MS were performed to analyze microbial composition and metabolites, respectively. At the genus level, the relative abundance of Rikenellaceae_RC9_gut_group was significantly higher (p < 0.05) in the NM group than in the NC group. The relative abundance of Treponema sp. was significantly lower (p < 0.05) in the NM group than in the NC group. In billy goats, the relative abundances of UCG-005 and Rikenellaceae_RC9_gut_group were significantly higher (p < 0.05) in the BH group than in the BC group. The relative abundance of Treponema sp. was significantly lower (p < 0.05) in the BL, BM, and BH groups than in the BC group. Furthermore, metabolomic analysis revealed that B. subtilis significantly altered the concentrations of glucose metabolism modulators (1-deoxynojirimycin, 1-DNJ) and certain bioactive peptides. Many amino acid metabolic pathways were also enriched. Correlation analysis demonstrated close connections between differential metabolites and the top 10 bacterial genera in fecal samples. These results provide new insights into the impact of B. subtilis on the microbial community and metabolic profile of the feces of Leizhou goats. In this experiment, the appropriate doses of B. subtilis for nanny goats and billy goats were 5 g/d and 7.5 g/d, respectively, but the optimal doses still need to be verified based on performance-based feeding tests in the next study. Full article

Objectives: Aqueous mulberry leaf extract (MLE) contains 1-deoxynojirimycin (DNJ) and L-leucine (LL). This study investigated the effects of MLE, DNJ, and LL on lipid accumulation caused by palmitic acid (PA) in human hepatoma HepG2 cells, pro-inflammatory cytokine levels, and regulation of lipogenesis. Methods: PA was applied to HepG2 cells to generate a fatty liver in vitro model. Then, the cells were treated with MLE, DNJ, or LL for 24 h. Western blot analysis was performed to determine the protein expression levels of peroxisome proliferator-activated receptor gamma (PPAR-γ) and fatty acid synthase (FAS) in HepG2 cells. Results: Staining with Oil Red O (ORO) indicated that MLE, DNJ, and LL significantly decreased excessive lipid accumulation in HepG2 cells. Cytokine ELISA assay indicated that MLE, DNJ, and LL significantly decreased excessive pro-inflammatory cytokine levels in HepG2 cells. In addition, MLE, DNJ, and LL decreased the protein expression levels of PPAR-γ and FAS, suggesting a potential suppression of lipogenesis. Conclusions: Our results suggest that MLE, DNJ, and LL reduce lipid accumulation, pro-inflammatory cytokine levels, and the protein expressions of FAS and PPAR-γ in PA-induced fatty liver cells. Full article

Background: Morus alba L. (family Moraceae) is widely cultivated across the world and is well-known for its medicinal and nutritional value, especially its leaves. This study investigates the regional variation in mulberry leaf metabolites, focusing on alkaloids and flavonoids, and explores the influence of climatic and environmental factors on their biosynthesis using an integrated metabolomic and environmental analysis. Mulberry leaves, known for their medicinal and nutritional value, were collected from six regions across China, including Sichuan, Xinjiang, and Tibet. Methods: Untargeted metabolomics via UHPLC-MS was conducted. Differential metabolites were identified through multivariate analysis and annotated using the KEGG database. Redundancy analysis was used to link metabolite profiles with climatic data. Results: Mulberry leaves from six Chinese regions showed significant variation in total flavonoid content (TFC), total polyphenol content (TPC), and 1-Deoxynojirmycin (DNJ), with Tibet having the highest TFC and TPC, and Panzhihua the highest DNJ. Metabolomic analysis identified 3794 metabolites, revealing distinct regional clustering. A total of 79 differential metabolites were identified, which are enriched in pathways such as galactose metabolism and phenylalanine biosynthesis. Environmental factors, especially bio3, bio10, bio2, bio5, and bio20, strongly influenced metabolite profiles. Conclusions: The biosynthesis and accumulation of secondary metabolites in mulberry leaves are significantly influenced by region-specific environmental factors, particularly temperature, precipitation, and light. The identified differential metabolites are mainly enriched in galactose metabolism, arginine, and proline metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis. These pathways are closely associated with plant stress responses and the synthesis of secondary metabolites. The pronounced regional differences in metabolite profiles underscore the critical role of environmental factors in determining the chemical composition of mulberry leaves. This research provides valuable insights into the influence of climatic factors affecting the chemical composition of plants. It lays a theoretical foundation for the quality assessment and grading of mulberry leaves, providing scientific guidance for their targeted cultivation and utilization. Full article

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

Background: Probiotics have recently emerged as promising agents in the prevention and treatment of various human diseases. This study investigates the therapeutic potential of Weizmannia coagulans SA9 in the management of type 2 diabetes mellitus (T2DM). Methods: The in vitro antidiabetic activity of W. coagulans SA9 was primarily assessed via its α-glucosidase inhibitory capacity, complemented by metabolomic profiling to identify putative bioactive metabolites. The antidiabetic efficacy was further evaluated in a db/db mouse model, focusing on glucose tolerance, inflammatory biomarkers, and gut microbiota composition. Results: W. coagulans SA9 showed significant inhibitory effects on α-glucosidase and α-amylase, and DNJ and other active substances were detected in its culture supernatant. After 6 weeks of continuous administration, the fasting blood glucose level, glucose tolerance, and inflammation indexes of mice were significantly improved. Beneficial changes in the structure of the intestinal flora occurred after the probiotic intervention, as evidenced by a significant decrease in harmful bacteria (e.g., Aerococcus urinaeequi) and a significant enrichment of beneficial bacteria (e.g., Limosilactobacillus reuteri). Conclusions: W. coagulans SA9 exerts robust antidiabetic effects and holds promise as a novel strategy for the prevention and management of T2DM. 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