Search Results (19)

According to the World Health Organization, over 422 million people worldwide have diabetes, with the majority residing in low- and middle-income countries. Diabetes causes 1.5 million fatalities a year. The number of diabetes cases and its prevalence have progressively increased over the last few decades. This study aims to determine the phytochemicals in the edible part of Perkia javanica, predict their α-glucosidase inhibitory potential, one of the promising targets for diabetes, and then carry out in vitro and in vivo studies. The phytochemicals present in the n-butanol fraction of the methanol extract of P. javanica pods were analyzed using UHPLC-QTOF-MS/MS (Ultra-High-Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry). The UHPLC-QTOF analysis revealed the presence of 79 different compounds in the n-butanol fraction. Among these, six compounds demonstrated excellent binding affinities with α-glucosidase, surpassing the performance of two standard inhibitors, Miglitol and Voglibose. In vitro α-glucosidase inhibitory activities were assessed by the n-butanol fraction, followed by in vivo studies. According to the in vitro study, the inhibitory efficiency against α-glucosidase was determined to have an IC₅₀ value of 261.9 µg/mL. The in vivo findings revealed a significant reduction in blood glucose levels in Swiss albino mice treated with the same extract, decreasing from 462.66 mg/dL to 228.66 mg/dL. Additionally, the extract significantly increased the activity of the enzymes catalase and superoxide dismutase (SOD) and decreased the amount of malondialdehyde (MDA) in the liver and kidney tissue. The predicted physicochemical parameters indicated that most of the compounds would be excreted from the body after inhibition in the small intestine without being absorbed. Considering the low cost and wide availability of raw materials, P. javanica pods can serve as a good food supplement that may help prevent type 2 diabetes management. Full article

Diabetes is a chronic metabolic disorder of the endocrine system characterized by persistent hyperglycemia appears due to the deficiency or ineffective use of insulin. The glucose level of diabetic patients increases after every meal and medically recommended drugs are used to control hyperglycemia. Alpha-glucosidase inhibitors are used as antidiabetic medicine to delay the hydrolysis of complex carbohydrates. Acarbose, miglitol, and voglibose are commercial drugs but patients suffer side effects of flatulence, bloating, diarrhea, and loss of hunger. To explore a new antidiabetic drug, a series of benzotriazinone carboxamides was synthesized and their alpha-glucosidase inhibition potentials were measured using in vitro experiments. The compounds 14k and 14l were found to be strong inhibitors compared to the standard drug acarbose with IC₅₀ values of 27.13 ± 0.12 and 32.14 ± 0.11 μM, respectively. In silico study of 14k and 14l was carried out using molecular docking to identify the type of interactions developed between these compounds and enzyme sites. Both potent compounds 14k and 14l exhibited effective docking scores by making their interactions with selected amino acid residues. Chemical hardness and orbital energy gap values were investigated using DFT studies and results depicted affinity of 14k and 14l towards biological molecules. All computational findings were found to be in good agreement with in vitro results. Full article

Brown macroalgae (BMG) were used as carriers for ZnO (ZnO/BMG) and cobalt-doped ZnO (Co-ZnO/BMG) via facile microwave-assisted hydrothermal synthesis. The multifunctional structures of synthesized composites were evaluated as enhanced antioxidant and anti-diabetic agents based on the synergistic effects of ZnO, Co-ZnO, and BMG. BMG substrate incorporation and cobalt doping notably enhanced the bioactivity of the synthesized ZnO nanoparticles. As an antioxidant, the Co-ZnO/BMG composite exhibited highly effective scavenging properties for the common free reactive oxygen radicals (DPPH [89.6 ± 1.5%], nitric oxide [90.2 ± 1.3%], ABTS [87.7 ± 1.8%], and O₂^●− [46.7 ± 1.9%]) as compared to ascorbic acid. Additionally, its anti-diabetic activity was enhanced significantly and strongly inhibited essential oxidative enzymes (porcine α-amylase (90.6 ± 1.5%), crude α-amylase (84.3 ± 1.8%), pancreatic α-glucosidase (95.7 ± 1.4%), crude intestinal α-glucosidase (93.4 ± 1.8%), and amyloglucosidase (96.2 ± 1.4%)). Co-ZnO/BMG inhibitory activity was higher than that of miglitol, and in some cases, higher than or close to that of acarbose. Therefore, the synthetic Co-ZnO/BMG composite can be used as a commercial anti-diabetic and antioxidant agent, considering the cost and adverse side effects of current drugs. The results also demonstrate the impact of cobalt doping and BMG integration on the biological activity of ZnO. Full article

Background: We previously conducted a pilot randomized controlled trial “the MASTER study” and demonstrated that alpha-glucosidase inhibitor miglitol and a dipeptidyl peptidase-4 inhibitor sitagliptin modified postprandial plasma excursions of active glucagon-like peptide-1 (aGLP-1) and active gastric inhibitory polypeptide (aGIP), and miglitol treatment decreased body fat mass in patients with type 2 diabetes (T2D). However, the details regarding the relationships among postprandial plasma aGLP-1 and aGIP excursions, skeletal muscle mass, and body fat mass are unclear. Methods: We conducted a secondary analysis of the relationships among skeletal muscle mass index (SMI), total body fat mass index (TBFMI), and the incremental area under the curves (iAUC) of plasma aGLP-1 and aGIP excursions following mixed meal ingestion at baseline and after 24-week add-on treatment with either miglitol alone, sitagliptin alone, or their combination in T2D patients. Results: SMI was not changed after the 24-week treatment with miglitol and/or sitagliptin. TBFMI was reduced and the rates of aGIP-iAUC change were lowered in the two groups treated with miglitol, although their correlations did not reach statistical significance. We observed a positive correlation between the rates of aGIP-iAUC and TBFMI changes and a negative correlation between the rates of TBFMI and SMI changes in T2D patients treated with sitagliptin alone whose rates of aGIP-iAUC change were elevated. Conclusions: Collectively, although T2D patients treated with miglitol and/or sitagliptin did not show altered SMI after 24-week treatment, the current study suggests that there are possible interrelationships among postprandial plasma aGIP excursion modified by sitagliptin, skeletal muscle mass, and body fat mass. Full article

Type 2 diabetes mellitus (T2DM) is the metabolic disease with the highest morbidity rates worldwide. The condition is characterized by hyperglycemia, insulin resistance, hyperlipidemia, and chronic inflammation, among other detrimental conditions. These decrease the efficiency of the immune system, leading to an increase in the susceptibility to bacterial infections. Maintaining an optimal blood glucose level is crucial in relation to the treatment of T2DM, because if the level of this carbohydrate is lowered, the risk of infections can be reduced. Currently, this is achieved using synthetic drug treatments that seek to moderately inhibit digestive enzymes (e.g., α-amylase and α-glucosidase), such as acarbose, voglibose, miglitol, etc. However, the use of these compounds also generates unwanted side effects such as nausea, diarrhea, stomach aches and a loss of appetite. Therefore, there is an increasing demand to find effective and safe alternatives for treating T2DM, such as herbal treatments. As a result, there has been a search for possible drugs from plants with both antidiabetic and antibacterial activity. This study presents a review of the molecular and cellular mechanisms of T2DM, secondary effects of the disease such as bacterial infections, and general comprehension of synthetic and natural product treatments to help patients. Full article

The kaolinite sheets were scrolled by sonication-induced chemical delamination processes into well-developed nanotubes (KNs) which were used as substrates for microwave-based ZnO nanoparticles (ZnO/KNs). The biological activities of synthetic ZnO/KNs structures, in terms of the antioxidant and antidiabetic properties, were assessed in comparative studies with the separated phases of the synthetic ZnO and KNs as well as the commercially used ZnO. The KNs substrate resulted in a notable enhancement in the antioxidant and antidiabetic properties of ZnO, which was assigned positive influence on the surface area, interactive interfaces, charge separation, and agglomeration properties of ZnO in addition to the detectable bioactive properties of the KNs structure. The ZnO/KNs structure achieved remarkable scavenging efficiencies for 1, 1-diphenyl-2-picrylhydrazil (DPPH) (89.8 ± 1.57%), nitric oxide (90.6 ± 1.63%), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) (86.8 ± 1.28%), and superoxide (43.9 ± 1.72%) radicals. Additionally, it shows high inhibition effects on porcine α-amylase (84.3 ± 1.92%), crude α-amylase (70.6 ± 1.37%), pancreatic α-Glucosidase (94.7 ± 1.54%), crude α-Glucosidase (95.4 ± 1.64%), and amyloglucosidase (95.3 ± 1.32%) enzymes. This antidiabetic activity is significantly higher than the activity of miglitol and close to or slightly higher than acarbose, which leads us to recommend the use of ZnO/KNs when considering the cost and side effects of the commercially used drugs. Full article

Green ZnO-decorated acid-activated bentonite-mediated curcumin extract (ZnO@CU/BE) was prepared as a multifunctional antioxidant and antidiabetic agent based on the extract of curcumin, which was used as a reducing and capping reagent. ZnO@CU/BE showed notably enhanced antioxidant properties against nitric oxide (88.6 ± 1.58%), 1,1-diphenyl-2-picrylhydrazil (90.2 ± 1.76%), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (87.3 ± 1.61%), and superoxide (39.5 ± 1.12%) radicals. These percentages are higher than the reported values of ascorbic acid as a standard and the integrated components of the structure (CU, BE/CU, and ZnO). This signifies the impact of the bentonite substrate on enhancing the solubility, stability, dispersion, and release rate of the intercalated curcumin-based phytochemicals, in addition to enhancing the exposure interface of ZnO nanoparticles. Therefore, effective antidiabetic properties were observed, with significant inhibition effects on porcine pancreatic α-amylase (76.8 ± 1.87%), murine pancreatic α-amylase (56.5 ± 1.67%), pancreatic α-glucosidase (96.5 ± 1.07%), murine intestinal α-glucosidase (92.5 ± 1.10%), and amyloglucosidase (93.7 ± 1.55%) enzymes. These values are higher than those determined using commercial miglitol and are close to the values measured using acarbose. Hence, the structure can be applied as an antioxidant and antidiabetic agent. Full article

Green zinc-metal-pillared bentonite mediated curcumin extract (Zn@CN/BE) was synthesized and characterized as a low-cost and multifunctional (curcumin-based phytochemicals, zinc-capped curcumin, zinc/curcumin complexes, and zinc-pillared bentonite) antioxidant and antidiabetic agent with enhanced activity. The activities of the Zn@CN/BE structure were assessed in comparison with curcumin and ZnO as individual components and in the presence of miglitol and acarbose commercial drugs as controls. The structure validated remarkable antioxidant activities against the common oxidizing radicals (nitric oxide (94.7 ± 1.83%), DPPH (96.4 ± 1.63%), ABTS (92.8 ± 1.33%), and superoxide (62.3 ± 1.63 %)) and inhibition activities against the main oxidizing enzymes (porcine α-amylase (89.3 ± 1.13%), murine α-amylase (70.8 ± 1.54%), pancreatic α-Glucosidase (99.3 ± 1.23%), intestinal α-Glucosidase (97.7 ± 1.24%), and amyloglucosidase (98.4 ± 1.64%)). The reported activities are higher than the activities of individual components and the studied ascorbic acid as well as the commercial drugs. This enhancement effect was assigned to the impact of the zinc pillaring process within the curcumin/bentonite host, which induced the stability, dispersions, and interactive interface of the essential active compounds in addition to the solubility and release rate of the intercalated curcumin extract. This paper recommends the application of the Zn@CN/BE structure as an enhanced, low-cost, biocompatible, safe, and simply produced antioxidant and antidiabetic agent. Full article

Hyperpigmentation is a common condition that causes darker spots or patches on the skin, which often look brown, black, gray, red, or pink. This results in unresolved psychological impact due to high anxiety, depression, and somatoform disorder. We aimed to repurpose an antidiabetic drug, miglitol, as an effective compound against hyperpigmentation when applied as a cosmeceutical agent. The present study investigated the antimelanogenic effects of miglitol and the trehalase inhibitor validamycin A. Miglitol in isolation exhibited no cytotoxicity and significantly reduced the melanin production and intracellular tyrosinase activity in B16F10 melanoma cells. The Western blotting results showed that miglitol reduces the expression of melanogenic regulatory factors, including tyrosinase, tyrosinase-related protein (TRP)-1, TRP-2, and microphthalmia-associated transcription factor (MITF). Mechanistically, miglitol appears to suppress melanin synthesis through cAMP-dependent protein kinase (PKA)-dependent downregulation of MITF, a master transcription factor in melanogenesis. The antimelanogenic effects of miglitol was mediated by downregulation of the p38 signaling pathway and upregulation of extracellular signal-regulated kinase (ERK). Moreover, miglitol decreases P-GSK3β and β-catenin levels compared to those in the untreated group. However, miglitol activated P-β-catenin expression compared to that in the untreated group. Finally, we tested the potential of miglitol in topical application through primary human skin irritation tests on the normal skin (upper back) of 33 volunteers. In these assays, miglitol (125 and 250 μM) did not induce any adverse reactions. Taken together, these findings suggest that the regulation of melanogenesis by miglitol may be mediated by the PKA, MAPK, and GSK3β/β-Catenin signaling pathways and that miglitol might provide new insights into drug repurposing for the treatment of hyperpigmentation symptoms. Full article

Diabetes is a chronic disease with a high mortality rate worldwide and can cause other diseases such as kidney damage, narrowing of blood vessels, and heart disease. The concomitant use of drugs such as metformin, sulfonylurea, miglitol, and acarbose may cause side effects with long-term administration. Therefore, natural ingredients are the best choice, considering that their long-term side effects are not significant. One of the compounds that can be used as a candidate antidiabetic is mangostin; however, information on the molecular mechanism needs to be further analyzed through molecular docking, simulating molecular dynamics, and testing the in silico antidiabetic potential. This study focused on modeling the protein structure, molecular docking, and molecular dynamics simulations and analyses. This process produces RMSD values, free energies, and intermolecular hydrogen bonding. Based on the analysis results, all molecular dynamics simulations can occur under physiological conditions, and γ-mangostin is the best among the test compounds. Full article

Diabetes mellitus is a chronic metabolic disorder in which the pancreas secretes insulin but the body cells do not recognize it. As a result, carbohydrate metabolism causes hyperglycemia, which may be fatal for various organs. This disease is increasing day by day and it is prevalent among people of all ages, including young adults and children. Acarbose and miglitol are famous alpha-glucosidase inhibitors but they complicate patients with the problems of flatulence, pain, bloating, diarrhea, and loss of appetite. To overcome these challenges, it is crucial to discover new anti-diabetic drugs with minimal side effects. For this purpose, benzotriazinone sulfonamides were synthesized and their structures were characterized by FT-IR, ¹H-NMR and ¹³C-NMR spectroscopy. In vitro alpha-glucosidase inhibition studies of all synthesized hybrids were conducted using the spectrophotometric method. The synthesized compounds revealed moderate-to-good inhibition activity; in particular, nitro derivatives 12e and 12f were found to be the most effective inhibitors against this enzyme, with IC₅₀ values of 32.37 ± 0.15 µM and 37.75 ± 0.11 µM. In silico studies, including molecular docking as well as DFT analysis, also strengthened the experimental findings. Both leading compounds 12e and 12f showed strong hydrogen bonding interactions within the enzyme cavity. DFT studies also reinforced the strong binding interactions of these derivatives with biological molecules due to their lowest chemical hardness values and lowest orbital energy gap values. Full article

Alpha-glucosidase inhibitor (αGIs)-induced pneumatosis intestinalis (PI) has been narrated in case reports but never systematically investigated. This study aimed to investigate the concurrency of PI and αGIs. A literature search was performed in PubMed, Google Scholar, WorldCat, and the Directory of Open-Access Journals (DOAJ) by using the keywords “pneumatosis intestinalis”, “alpha-glucosidase inhibitors”, and “diabetes”. In total, 29 cases of αGIs-induced PI in 28 articles were included. There were 11 men, 17 women, and one undefined sex, with a median age of 67. The most used αGI was voglibose (44.8%), followed by acarbose (41.4%) and miglitol (6.8%). Nine (31%) patients reported concomitant use of prednisone/prednisolone with or without immunosuppressants. The main symptoms were abdominal pain (54.5%) and distention (50%). The ascending colon (55.2%) and the ileum (34.5%) were the most affected. Nineteen (65.5%) patients had comorbidities. Patients with comorbidities had higher rates of air in body cavities, the portal vein, extraintestinal tissues, and the wall of the small intestine. Only one patient was found to have non-occlusive mesenteric ischemia. Twenty-five patients were treated with conservative therapy alone, and two patients received surgical intervention. All patients recovered. In conclusion, comorbidities, glucocorticoids, and immunosuppressants aggravate αGIs-induced PI. Conservative therapy is recommended when treating αGIs-induced PI. Full article

Trichoderma reesei is a high-yield producer of cellulase for applications in lignocellulosic biomass conversion, but its cellulase production requires induction. A mixture of glucose and β-disaccharide has been demonstrated to achieve high-level cellulase production. However, as inducers, β-disaccharides are prone to be hydrolyzed by β-glucosidase (BGL) during fermentation, therefore β-disaccharides need to be supplemented through feeding to overcome this problem. Here, miglitol, an α-glucosidase inhibitor, was investigated as a BGL inhibitor, and exhibited an IC₅₀ value of 2.93 μg/mL. The cellulase titer was more than two-fold when miglitol was added to the fermentation medium of T. reesei. This method was similar to the prokaryotic expression system using unmetabolized isopropyl-β-D-thiogalactopyranoside (IPTG) as the inducer instead of lactose to continuously induce gene expression. However, cellulase activity was not enhanced with BGL inhibition when lactose or cellulose was used as an inducer, which demonstrated that the transglycosidase activity of BGL is important for the inducible activity of lactose and cellulose. This novel method demonstrates potential in stimulating cellulase production and provides a promising system for T. reesei protein expression. Full article

Lytic transglycosylases such as Slt35 from E. coli are enzymes involved in bacterial cell wall remodelling and recycling, which represent potential targets for novel antibacterial agents. Here, we investigated a series of known glycosidase inhibitors for their ability to inhibit Slt35. While glycosidase inhibitors such as 1-deoxynojirimycin, castanospermine, thiamet G and miglitol had no effect, the phenothiazinium dye thionine acetate was found to be a weak inhibitor. IC₅₀ values and binding constants for thionine acetate were similar for Slt35 and the hen egg white lysozyme. Molecular docking simulations suggest that thionine binds to the active site of both Slt35 and lysozyme, although it does not make direct interactions with the side-chain of the catalytic Asp and Glu residues as might be expected based on other inhibitors. Thionine acetate also increased the potency of the beta-lactam antibiotic ampicillin against a laboratory strain of E. coli. Full article

Diabetes mellitus, one of the most common endocrine-metabolic disorders, has caused significant morbidity and mortality worldwide. To avoid sugar digestion and postprandial hyperglycemia, it is necessary to inhibit α-glucosidase, a digestive enzyme with an important role in carbohydrate digestion. The criteria for the selection of alkaloids are based on their in vitro and in vivo activities on glucose modulation. The current study assessed the bonding potential of isolated alkaloids with the targeted protein. For this purpose, the 3D structure of the target protein (α-glucosidase) was reproduced using MODELLER 9.20. The modeled 3D structure was then validated and confirmed by using the RAMPAGE, ERRAT, and Verify3D online servers. The molecular docking of 32 alkaloids reported as α-glucosidase inhibitors, along with reference compounds (acarbose and miglitol), was done through MOE-Dock applied in MOE software to predict the binding modes of these drug-like compounds. The results revealed that nummularine-R and vindoline possess striking interactions with active site residues of the target protein, and were analogous to reference ligands. In conclusion, the current study provided a computational background to the α-glucosidase inhibitors tested. This novel information should facilitate the development of new and effective therapeutic compounds for the treatment of diabetes mellitus. Full article