Α-glucosidase Inhibitory Activity Research Articles

Mechanisms of inhibition of advanced glycation end-products (AGEs) and α-glucosidase by Heliotropium bacciferum: Spectroscopic and molecular docking analysis

Diabetes mellitus is characterized by hyperglycemia that makes insulin more prone to glycation and form advanced glycation end products (AGEs). Here, we report the effect of glyoxal (GO) on the formation of AGEs using human insulin as model protein and their structural modifications. The present investigation also reports the anti-AGE potential of Heliotropium bacciferum (Leaf) extracts. The phytochemical analysis of H. bacciferum revealed that free phenolic extract contains higher amount of total phenolic (3901.58 ± 17.06 mg GAE/100 g) and total flavonoid content (30.41 ± 0.32 mg QE/100 g) when compared to bound phenolic extract. Naringin and caffeic acid were identified as the major phenolic ingredients by UPLC-PAD method. Furthermore, bound phenolics extract showed significantly higher DPPH and superoxide radicals scavenging activity (IC50 17.53 ± 0.36 μg/mL and 0.306 ± 0.038 mg/ mL, respectively) (p ≤ 0.05). Besides, the bound phenolics extract also showed significant (p ≤ 0.05) chelating power (IC50 0.063) compared to free phenolic extract. In addition, bound phenolic extract could efficiently trap GO under physiological conditions. Spectroscopic investigation of GO-modified insulin illustrated changes in the tertiary structure of insulin and formation of AGEs. On the other hand, no significant alteration in secondary structure was observed by far UV-CD measurement. Furthermore, H. bacciferum extract inhibited α-glucosidase activity and AGEs formation implicated in diabetes. Molecular docking analysis depicted that GO bind with human insulin in both chains and forms a stable complex with TYR A: 14, LEU A:13, ASN B:3, SER A:12 amino acid residues with binding energy of – 2.53 kcal/mol. However, caffeic acid binds to ASN A:18 and GLU A:17 residues of insulin with lower binding energy of −4.67 kcal/mol, suggesting its higher affinity towards human insulin compared to GO. Our finding showed promising activity of H. bacciferum against AGEs and its complications. The major phenolics like caffeic acid, naringin and their derivatives could be exploited for the drug development for management of AGEs in diabetes.

Bioactive α-Pyrone Analogs from the Endophytic Fungus Diaporthe sp. CB10100: α-Glucosidase Inhibitory Activity, Molecular Docking, and Molecular Dynamics Studies.

Two α-pyrone analogs were isolated from the endophytic fungus Diaporthe sp. CB10100, which is derived from the medicinal plant Sinomenium acutum. These analogs included a new compound, diaporpyrone F (3), and a known compound, diaporpyrone D (4). The structure of 3 was identified by a comprehensive examination of HRESIMS, 1D and 2D NMR spectroscopic data. Bioinformatics analysis revealed that biosynthetic gene clusters for α-pyrone analogs are common in fungi of Diaporthe species. The in vitro α-glucosidase inhibitory activity and antibacterial assay of 4 revealed that it has a 46.40% inhibitory effect on α-glucosidase at 800 μM, while no antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), Mycolicibacterium (Mycobacterium) smegmatis or Klebsiella pneumoniae at 64 μg/mL. Molecular docking and molecular dynamics simulations of 4 with α-glucosidase further suggested that the compounds are potential α-glucosidase inhibitors. Therefore, α-pyrone analogs can be used as lead compounds for α-glucosidase inhibitors in more in-depth studies.

Aloe juvenna Brandham & S.Carter as α-Amylase Inhibitor and Hypoglycaemic Agent with Anti-inflammatory Properties for Diabetes Management.

Despite Aloe's traditional use, Aloe juvenna Brandham & S.Carter is poorly characterized. Other Aloes are known for their antidiabetic activity. This study describes the antidiabetic potentials and phytoconstituents of the A. juvenna leaves methanolic extract (AJME). Twenty-six phytoconstituents of AJME were described using HPLC/MS-MS. Lupeol and vitexin were isolated using column chromatography. The antidiabetic activity of AJME was investigated using an in vivo high-fat diet/streptozotocin-induced diabetic rat model and in vitro α-glucosidase and α-amylase inhibitory activity assays. AJME demonstrated its α-amylase inhibitory activity (IC50=313±39.9 ppm) with no effect on α-glucosidase. In vivo, AJME dose-dependently improved hyperglycaemia in a high-fat diet/streptozotocin-induced diabetic rat model. Notably, the higher dose (1600 mg/kg) of AJME significantly downregulated serum interleukin-6, tumor necrosis factor-α, and matrix metalloproteinase-1 genes, suggesting its anti-inflammatory effect. These findings indicate AJME's potential as a significant antidiabetic agent through its α-amylase inhibition, hypoglycaemic, and anti-inflammatory properties.

Synthesis, anti-α-glucosidase activity, inhibition interaction, and anti-diabetic activity of novel cryptolepine derivatives

To find potential α-glucosidase inhibitors, thirty-seven cryptolepine derivatives (FM1 ∼ 37) were designed and synthesized. Compared to parent compound cryptolepine (IC50 = 440.12 ± 50.04 μM) and positive compound acarbose (IC50 = 523.42 ± 42.15 μM), all synthesized compounds showed stronger α-glucosidase inhibitory activities with IC50 values of 6.45 ± 0.68 ∼ 48.03 ± 2.18 μM. The strongest compound FM25 (IC50 = 6.45 ± 0.68 μM) was proved to be a mixed-type inhibitor with Ki value of 0.18 μM. Fluorescence quenching results clarified that the binding of FM25 with α-glucosidase quenched the fluorescence of α-glucosidase in a static process. CD spectra, 3D spectra, and docking results indicated that the binding of FM25 with α-glucosidase led to the conformation change of α-glucosidase to reduce enzyme activity. In vivo experiments showed FM25 could reduce the fasting blood glucose and improve glucose tolerance and hypertension in STZ-induced diabetes mice.

Three new constituents from the stems of Knema globularia and their α-glucosidase inhibitory activity

Three new metabolites (1−3) were isolated from the stems of Knema globularia, along with five known compounds, including kaempferol (4), quercetin (5), isovanillic acid (6), protocatechuic acid (7), and gallic acid (8). Their structures were deduced using NMR spectroscopic, mass spectrometric analyses, and literature data. The absolute configurations of 1−3 were established by electronic circular dichroism (ECD) spectroscopy. α-Glucosidase inhibitory activities of those compounds were evaluated using a spectrophotometric method, compounds 1−3 showed very strong effects towards α-glucosidase with IC50 values 1.59, 0.58 and 1.37 µM, respectively (the positive control, acarbose, IC50 93.63 µM). Simultaneously, enzyme kinetics study indicated that 2 was a mix-type inhibitor. 2 interacted well in the active site of α-glucosidase enzyme, primarily through hydrogen bonds and hydrophobic interactions.

Phytochemical Profile and Bioactivity of Bound Polyphenols Released from Rosa roxburghii Fruit Pomace Dietary Fiber by Solid-State Fermentation with Aspergillus niger.

This study aimed to investigate the phytochemical profile, bioactivity, and release mechanism of bound polyphenols (BPs) released from Rosa roxburghii fruit pomace insoluble dietary fiber (RPDF) through solid-state fermentation (SSF) with Aspergillus niger. The results indicated that the amount of BPs released from RPDF through SSF was 17.22 mg GAE/g DW, which was significantly higher than that achieved through alkaline hydrolysis extraction (5.33 mg GAE/g DW). The BPs released through SSF exhibited superior antioxidant and α-glucosidase inhibitory activities compared to that released through alkaline hydrolysis. Chemical composition analysis revealed that SSF released several main compounds, including ellagic acid, epigallocatechin, p-hydroxybenzoic acid, quercetin, and 3,4-dihydroxyphenylpropionic acid. Mechanism analysis indicated that the disruption of tight structure, chemical bonds, and hemicellulose was crucial for the release of BPs from RPDF. This study provides valuable information on the potential application of SSF for the efficient release of BPs from RPDF, contributing to the utilization of RPDF as a functional food ingredient.

Phenolic constituents from the branches of Viburnum chinshanense as potential α-amylase and α-glucosidase inhibitory agents

This paper reports the isolation of two undescribed phenolic glycosides (1 and 2), together with seven known compounds (3–9) from the branches of Viburnum chinshanense. The structures of undescribed compounds were elucidated by comprehensive spectroscopic methods (1D NMR, 2D NMR, and HRESIMS). The sugar units of compounds 1 and 2 were identified by acid hydrolysis and HPLC analysis of the chiral derivatives of the monosaccharides. Furthermore, the α‑amylase and α-glucosidase inhibitory activities of all isolates were evaluated and compounds 1, 5, and 8 displayed potential α‑amylase and α-glucosidase inhibitory activities. The molecular docking analyses of compounds 1 and 8 with the potent inhibition towards the target enzymes were also performed.

Investigation of the antidiabetic and probiotic properties of lactic acid bacteria isolated from some ethnic fermented foods of Darjeeling District

BackgroundIndigenous communities residing in the Darjeeling Himalayan region and its adjacent hilly areas have a deeply rooted cultural tradition of consuming a diverse range of vegetable and milk-based fermented products, believed to confer various health advantages. With this traditional knowledge, lactic acid bacteria (LAB) were isolated from popular fermented foods such as Chhurpi (derived from Bos grunniens milk), Gundruk (made from Brassica juncea leaves), Sinki (derived from Raphanus sativus taproots), and Kinema (produced from Glycine max beans). This study aimed to investigate the probiotic properties of the prevalent LABs, including aggregation properties, bile salt hydrolase activities, survival under gastro-inhibitory conditions, safety evaluations, and their potential health-promoting attributes, with a specific focus on inhibiting α-amylase and α-glucosidase enzymes.ResultsFive of the LAB isolates demonstrated notable viability rates exceeding 85% when exposed to gastro-inhibitory challenges. Based on 16S rRNA gene sequencing, these isolates were identified as Pediococcus pentosaceus (isolate GAD), Lactobacillus plantarum (isolates KAD and CAD), Lactobacillus brevis (isolate SAD), and Lactiplantibacillus plantarum (isolate CMD). These LAB isolates exhibited versatile carbon source utilization, significant auto- and co-aggregation, and bile salt hydrolase (BSH) properties. Auto-aggregation capacity notably increased over time, ranging from 30 to 150 min, with percentage increments from 4.83 ± 1.92% to 67.60 ± 5.93%. L. brevis SAD displayed the highest co-aggregation increment (%) against Staphylococcus aureus, while L. plantarum KAD demonstrated potent antimicrobial activity. In vitro analyses postulated potential health benefits related to antidiabetic properties, particularly inhibiting α-amylase and α-glucosidase enzymes. L. brevis SAD exhibited the highest α-glucosidase inhibitory activity, while L. plantarum KAD displayed the most potent α-amylase inhibitory activity. Comprehensive safety assessments, including antibiotic susceptibility profiling, hemolytic activity evaluation, and in vivo acute toxicity studies, confirmed the suitability of these LAB isolates for human consumption.ConclusionsThe isolates show promising probiotic characteristics and significant potential in addressing metabolic health. These results carry substantial scientific implications, suggesting the pharmaceutical-based applications of these traditional fermented foods. Further in vivo investigation is recommended to fully elucidate and exploit the health benefits of these LAB isolates, opening avenues for potential therapeutic interventions and the development of functional foods.

α-glucosidase Inhibitory Activity of Probiotic Isolate LBSU9 Isolated from Traditional Food “Trites”: a Preliminary Study

As the prevalence of type 2 diabetes mellitus continues to increase over the years, research into antidiabetic drugs needs to continue. Probiotics are non-pathogenic microorganisms that have potential as α-glucosidase inhibitors. This study aimed to characterize and determine the α-glucosidase inhibitor activity of LBSU9 isolate, a probiotic isolated from "trites," a traditional food of North Sumatra. The results showed that LBSU9 had bacillus morphology, Gram positive, negative catalase test, TSIA (Triple Sugar Iron Agar) A/A test and non-hemolysis. LBSU9 had good tolerance to simulated gastric acid and bile salts, with growth percentages of 66.54% and 64.74%. LBSU9 also has potent antimicrobial activity against S.aureus and E.coli, with 20 mm and 17 mm inhibition zones, respectively. The alpha-glucosidase inhibitor activity of LBSU9 was 98.4% greater than that of acarbose, which was 97%. Based on the results of this study, it is concluded that LBSU9 isolate has the potential to be a complementary therapy to prevent or treat type 2 diabetes mellitus

Morusacerane: A new gammacerane triterpenoid from the trunk of Morus Alba linn. with α-glucosidase inhibitory activity

This phytochemistry investigation on the trunk of Morus alba L. resulted in the isolation of three triterpenoids, including a new gammacerane triterpenoid – morusacerane (1); along with two known compounds of betulinic acid (2) and ursolic acid (3). The structure elucidation was thoroughly conducted based on 1D, 2D-NMR and HRESIMS spectra, followed by a comparison with existing literatures. The evaluation on α-glucosidase inhibitory exhibited the great potential of the application of these isolated compounds in diabetes treatments. The results show that morusacerane (1), betulinic acid (2), and ursolic acid (3) demonstrate the strong inhibitory with the IC50 values of 106.1, 11.12, and 7.20 μM, respectively. All of these compounds interacted well with the allosteric site enzyme α-glucosidase MAL32 through H-bonds and hydrophobic interaction.

Simultaneous high-performance liquid chromatography analysis of anthraquinones in sicklepod sprouts with α-glucosidase inhibitory activity.

Sicklepod [Cassia obtusifolia L. syn Senna obtusifolia (L.) H.S. Irwin & Barneby, Fabaceae] sprouts are promising ingredients with health-promoting benefits. Notwithstanding, the pharmacologically active compounds in sicklepod sprouts have not been studied or analysed in detail. This study aimed to isolate and structurally identify phytochemicals showing α-glucosidase inhibitory activity in sicklepod sprouts and simultaneously quantify the compounds in the sprouts to determine the optimal cultivation method and germination time to maximise active compounds. A simultaneous high-performance liquid chromatography-ultraviolet (HPLC-UV) method with high sensitivity and accuracy was developed and used to analyse time-dependent changes in anthraquinone content during sicklepod germination. Thirteen anthraquinones were isolated and identified, of which six-chrysoobtusin, emodin, 1-O-methyl-2-methoxychrysophanol, 7-O-methylobtusin, chrysophanol, and physcion-showed moderate α-glucosidase inhibitory activity. The maximum content of anthraquinones in a sprout was observed on Day 5 under both light and dark conditions. The findings of this study revealed that sicklepod sprouts which are promising functional food materials contain a variety of anthraquinones.

Enzymatic synthesis of Artemisia capillaris-derived prebiotic oligosaccharide using Leuconostoc mesenteroides MKSR dextransucrase and its potential health functional effects

This study focuses on the enzymatic synthesis of prebiotic oligosaccharide from Artemisia capillaris (AC) using Leuconostoc mesenteroides MKSR dextransucrase and explores their antidiabetic, antidementia, and antioxidant effects through in vitro experiments. A Box-Behnken design was used to optimize transglycosylation conditions to produce Artemisia capillaris-derived oligosaccharide (ACOD) containing isomaltooligosaccahrides (IMO), dextran, and A. capillaris-derived substances with high α-glucosidase inhibition (AGI). The optimized conditions were 3.62 brix of AC, 182.54 mM sucrose, and 11.304 mM maltose. ACOD completely inhibited α-glucosidase activity, with 1.52-fold increase compared to other samples, such as OD (IMO and dextran, transglycosylated by dextransucrase without AC) and AC + OD (a simple mixture of AC and OD). Additionally, ACOD showed noteworthy acetylcholinesterase (103.91%) and butyrylcholinesterase (103.30%) inhibitory activity and potent antioxidant properties in terms of DPPH radical scavenging activity (70.04%), reducing power (100%), and ferric reducing antioxidant power (FRAP). ACOD (3.60) showed a higher prebiotic index compared with AC (-23.11), OD (-2.27), and AC + OD (-9.12). In conclusion, ACOD offers enhanced multi-biological activities as a potential health-functional prebiotic. These findings hold promise for applications in functional foods and pharmaceuticals, expanding our understanding of prebiotic functionality.

Enrichment and purification of Torreya grandis peptides by macroporous resin and its hypoglycemic mechanism revealed by transcriptome analysis

The objective of this study was to develop an efficient strategy to prepare high-hypoglycemic efficacy Torreya grandis meal peptides with macroporous resin and investigate the underlying mechanisms through transcriptome analysis. The evaluation of adsorption and desorption abilities of Torreya grandis meal peptides (TGPs) on six different microporous resins were compared. The hypoglycemic activity of prepared TGPs was further measured in a Zebrafish diabetic model, and the underlying mechanisms were investigated through transcriptome analysis. Results showed that DA201-C exhibited the highest adsorption and desorption capacities. After DA201-C resin enrichment, the α-glucosidase inhibition and α-amylase inhibition activities of TGPs in 75% ethanol eluate (TGPs-75) both significantly increased (the IC50 values are 0.41 mg/mL and 1.08 mg/mL, respectively). The in vivo data showed that TGPs-75 remarkably reduced blood glucose concentrations to 7.8, 15.6, and 31.2 μg/mL in an high-sugar-high-fat-treated (HSHF-treated) Zebrafish diabetic model and exerted obvious hypoglycemic activity. According to transcriptome analysis, 382 genes were significantly differentially expressed (229 up-regulated and 153 down-regulated) after TGPs-75 pretreatment. The main functions of these genes are related to gluconeogenesis and insulin resistance. The findings from the present study suggested that TGPs-75 produced positive hypoglycemic efficacy and showed potential to provide a scientific basis for its further utilization as a dietary supplement or an ingredient in functional foods.

Green Synthesis and Anti-Diabetic Potential of Berberis vulgaris Silver Nanoparticles: A Promising Approach for Natural Therapeutics

This study reports the green synthesis of Berberis vulgaris root water-mediated silver nanoparticles (BvAgNPs) showcasing high purity, size-controlled morphology, and potential anti-diabetic activity. Characterization techniques confirmed the successful synthesis of predominantly spherical BvAgNPs within the 15–70 nm range, coated with organic moieties from the extract. Remarkably, BvAgNPs exhibited significantly enhanced α-amylase and α-glucosidase inhibitory activity compared to the extract alone, with inhibition higher for α-amylase. This superior anti-diabetic activity, even comparable to the standard drug Acarbose for α-amylase inhibition, highlights the potential of BvAgNPs as natural and potentially less-toxic alternatives in diabetes management. Further research on their mechanisms and in vivo efficiency is warranted to pave the way for their future application as promising anti-diabetic therapeutics.

Phytochemical Screening and Antidiabetic Activity of Aqueous Extract of Evolvulus Alsinoides Leaves: An In Vitro and In Silico Study.

Nowadays, diabetes mellitus has become common worldwide due to changes in lifestyle, sedentary life, alterations in food habits, and other genetic and environmental factors. It is necessary to create awareness about the growing pandemic. To evaluate the antidiabetic potential of Evolvulus alsinoides. In vitro α-amylase inhibition and α-glucosidase inhibition activity. Molecular docking analysis. The plant is rich in naturally occurring phytocompound. The results of the study showed that E. alsinoides has the potential to inhibit the activity of alpha-amylase and alpha-glucosidase. Moreover, this result was validated using in silico molecular docking studies that showed a good binding affinity of one of the major phytocompound, caffeic acid, with molecules in the insulin signaling cascade. E. alsinoides has a potent antidiabetic activity and can be further employed in animal and human studies.

Valeriana jatamansi: Bioactive Compounds and their Medicinal Uses.

Valeriana jatamansi is a reputed perennial medicinal herb distributed throughout the world, where it is used in cytotoxicity, neuronal problems, insomnia, leishmania and acetylcholinesterase inhibitor, antioxidant, antiviral and α-glucosidase inhibition activities. This review describes the current state of chemical characterization of isolated metabolites, which are well accepted for the treatment of various ailments in the indigenous system of medicine. This comprehensive review covers previously published research articles and reviews up to 2023 with an emphasis on the structural characterization of isolated bioactive compounds using different analytical techniques. Furthermore, the present review also focuses on the detailed medicinal and pharmacological properties of isolated compounds from this threatened herb.

Plicatin C: A New Cinnamate Derivative from Mangrove-derived Fungus Aspergillus terreus DM62

Background: Marine fungi have been proven to be a new arsenal for the discovery of valuable secondary metabolites. Method:: Fungus strain Aspergillus terreus DM62 was initially fermentated using solid corn medium and PDA liquid medium. Subsequently, extensive chromatographic methods were applied to isolate the fermentation cultures of DM62, and the chemical structures of isolate compounds were elucidated by pectroscopic analyses and optical rotations comparison. Additionally, α-glucosidase and ATPcitrate lyase (ACL) inhibitory activities of isolate compounds were assessed to investigate their hypoglycemic and lipid-lowering activities. Result:: A new cinnamate derivative, plicati n C (1), together with 18 known compounds, were isolated from the solid and liquid state fermentations of A. terreus DM62. Activity evaluation showed that compounds 3, 6, and 8-10 exhibited stronger α-glucosidase inhibitory activities than acarbose at 400 μM, and butenolide 3, with an IC50 value of 21.5 μM, was discovered with significant ACL inhibitory activity for the first time. Conclusion:: This study not only discovered a new cinnamate derivative but also found butenolides with potent ACL inhibitory activity, which is favorable to clarify their pharmacological mechanism in the treatment of metabolic disease.

Alpha-amylase and Alpha-glucosidase Inhibitory Activities of Philippine Indigenous Medicinal Plants

In the Philippines, medicinal plants still provide the first line of therapeutic remedies and their reported efficacy in traditional treatments provides an opportunity for drug discovery and development. The study aimed to evaluate in vitro commonly used Philippine medicinal plants for their alpha-amylase and alpha-glucosidase inhibitory activities as potential sources of antidiabetic agents. The study emphasised the inhibitory activities of 54 medicinal plants against α-amylase and α-glucosidase enzymes. The findings revealed 7 medicinal plants with the highest alpha-glucosidase inhibitory activity of ≥ 50% and 3 with alpha-amylase inhibitory activity of ≥ 20%. Ethyl acetate extract of Cycas sp. exhibited the highest α-glucosidase inhibitory activity with 83.87% ± 1.52 followed by the aqueous extract of cf. Calyptranthera sp. With 82.07% ± 0.14 with Acarbose as the reference standard (99.71% ± 0.63) at 10µg/mL (w/v) concentration. For the alpha-amylase inhibitory assay, the highest bioactivity was observed in ethyl acetate extract of Curcuma longa L. (39.44% ± 1.56) with Acarbose as the reference standard (51.59% ± 0.98) at 10µg/mL (w/v) concentration. These findings suggest the potential of the above-mentioned plants as sources of alpha-amylase and alpha-glucosidase inhibitors that may be used as antidiabetic agents.

Anacardic acid derivatives with significant α-glucosidase inhibitory activity from Syzygium samarangense

Our continuous effort to search for antidiabetic constituents from the leaves of Syzygium samarangense resulted in the isolation of one new anacardic acid derivative, 2-[(Z)-nonadec-14-enyl]-6-hydroxylbenzoic acid (1) along with four known analogues (2−5). The new structure was elucidated by means of extensive spectroscopic data including 1D and 2D NMR along with HRESIMS. The anacardic acid derivatives were isolated from this species for the first time. All compounds exhibited significant inhibitory effect with IC50 value of 0.75−3.60 μM against α-glucosidase.

Microspheres as carriers of sea buckthorn carotenoids and tocols with antidiabetic potential: Effect of biopolymers, cross-linking and storage

The bioactivity of carotenoids and tocols is limited by their instability, hydrophobicity, and low bioavailability. Hence, the study aimed to design microspheres from sea buckthorn juice by ionotropic gelation to increase stability, ensure high content of carotenes, xanthophylls, tocopherols and tocotrienols and their antidiabetic activity. The effects of biopolymers, cross-linking and storage on the carotenoid and tocol profile of microspheres (identified and quantified by LC-PDA-QTOF-ESI-MS and UPLC-FL methods) and their in vitroα-amylase and α-glucosidase inhibitory activity were investigated. Microspheres containing sodium alginate/κ-carrageenan (4:1) had significantly high content of carotenoids and tocols, and antihyperglycemic activity (p < 0.05). The two-step cross-linking (1-calcium chloride, 2-chitosan) provided a 17% higher carotenoid content. Cross-linking with CaCl2 promoted high content of tocopherols but stability protection was provided by sodium alginate and CaCl2/chitosan (9:1) cross-linking (1.7-fold decrease in instability). The encapsulation using newly designed combinations of biopolymers and cross-linking could be an effective strategy to increase the stability and bioactivities of microspheres as nutraceuticals and smart food.