Α-glucosidase Enzyme Research Articles

Chemical Profile and Bioactivity of Rubus idaeus L. Fruits Grown in Conventional and Aeroponic Systems.

Raspberry (Rubus idaeus L.) is a fruit of great interest due to its aroma, nutritional properties, and the presence of many bioactive compounds. However, differences among cultivation systems can affect its composition and, consequently, its potential bioactivity. Herein, for the first time, raspberries grown in an aeroponic system were investigated for their chemical profile and antioxidant and anti-inflammatory activity, as well as their enzyme (α-glucosidase and pancreatic lipase) inhibitory properties in comparison to wild and conventionally cultivated fruits. High-performance liquid chromatography coupled with diode array detection (HPLC-DAD) analyses revealed the presence of gallic acid, caffeic acid, chlorogenic acid, p-coumaric acid, ferulic acid, rutin, and catechin in all the samples. The extracts exhibited in vitro anti-inflammatory activity (inhibition of nitric oxide production) regardless of the cultivation method. Of particular interest is the ability of raspberries to inhibit pancreatic lipase. With the exception of the β-carotene bleaching test, the raspberries grown in conventional and aeroponic systems were more active in terms of antioxidants than wild fruits, as evidenced by the ABTS (IC50 in the range 1.6-3.4 μg/mL), DPPH (IC50 in the range 8.9-28.3 μg/mL), and FRAP tests (24.6-44.9 μM Fe(II)/g). The raspberries from aeroponic cultivation were generally able to exert the same bioactivity as those obtained from both conventionally cultivated and wild fruits, supporting the consideration that in the future, this technology could reshape agriculture by mitigating resource constraints, fostering sustainable practices and increasing yields.

Investigation of in vitro Biological Activity from Extracts of Ruellia tuberosa.

<b>Background and Objective:</b> <i>Ruellia tuberosa</i> is a common plant in the Mekong Delta and is widely used in many Vietnamese folk remedies. This study was conducted to investigate the potential use of roots, stems, leaves of <i>Ruellia tuberosa</i> as antioxidant, antimicrobial, α-amylase and α-glucosidase inhibitors. <b>Materials and Methods:</b> The extracts were tested for their ability to inhibit the enzymes α-amylase and α-glucosidase associated with diabetes. The antioxidant activities of the extracts were evaluated using 2,2-Diphenyl-1-Picrylhydrazyl (DPPH) and 2,2-Azino-Bis-(3-Ethylbenzothiazoline-6-Sulfonic Acid) (ABTS), ferric reducing antioxidant power (FRAP), total antioxidant capacity (TAC) and reducing power (RP) assays. The antibacterial activity of extracts from <i>Ruellia tuberosa</i> was evaluated by the agar well diffusion method. <b>Results:</b> The root extract of <i>Ruellia tuberosa</i> has more polyphenols (32.49±0.72 mg GAE/g extract) and flavonoids (15.48±1.32 mg QE/g extract) than the other parts. Simultaneously, the root extract of <i>Ruellia tuberosa</i> has antioxidant activity (IC<sub>50</sub> values range from 117.67±2.82 to 569.20±7.68 μg/mL), inhibiting amylase (IC<sub>50</sub> = 266.72±10.58 μg/mL) and glucosidase (IC<sub>50</sub> = 147.13±3.58 μg/mL) enzymes more effectively than the other parts. Research results also show that extracts from <i>Ruellia tuberosa</i> are capable of inhibiting <i>Staphylococcus aureus</i>, <i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i> bacteria with minimum inhibitory concentrations ranging from 1280 to 10240 mg/mL. <b>Conclusion:</b> These results highlighted the potential using of <i>Ruellia tuberosa</i> extracts as natural antioxidant, antimicrobial, α-amylase and α-glucosidase inhibitors agents.

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.

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.

Real-life effectiveness 1 year after switching to avalglucosidase alfa in late-onset Pompe disease patients worsening on alglucosidase alfa therapy: A French cohort study.

Late-onset Pompe disease (LOPD) is characterized by a progressive myopathy resulting from a deficiency of acid α-glucosidase enzyme activity. Enzyme replacement therapy has been shown to be effective, but long-term treatment results vary. Avalglucosidase alfa demonstrated non-inferiority to alglucosidase alfa in a phase 3 study, allowing in France compassionate access for advanced LOPD patients unresponsive to alglucosidase alfa. Data from the French Pompe registry were analyzed for patients who benefited from a switch to avalglucosidase alfa with at least 1 year of follow-up. Respiratory (forced vital capacity [FVC]) and motor functions (Six-Minute Walk Test [6MWT]) were assessed before and 1 year after switching. Individual changes in FVC and 6MWT were expressed as slopes and statistical analyses were performed to compare values. Twenty-nine patients were included (mean age 56 years, 11 years of prior treatment). The FVC and 6MWT values remained stable. The individual analyses showed a stabilization of motor worsening: -1 m/year on the 6MWT after the switch versus -63 m/year the year before the switch (i.e., a worsening of 33%/year before vs. an improvement of 3%/year later). Respiratory data were not statistically different. At the group level, gait parameters improved slightly with a stabilization of previous worsening, but respiratory parameters showed limited changes. At the individual level, results were discordant, with some patients with a good motor or respiratory response and some with further worsening. Switching to avalglucosidase alfa demonstrated varied responses in advanced LOPD patients with failing alglucosidase alfa therapy, with a general improvement in motor stabilization.

Synthesis and biological (in vitro and in silico) screening of the 4-aryl-fused pyranopyrazole derivatives as enzyme (α-amylase, α-glucosidase, acetylcholinesterase & proteinase) inhibitors with anti-oxidant and cytotoxic activities

The development of single compound targeting dual/multiple proteins is an efficient approach to avoid the combined drug administration. Herein, based on the modification of the previously reported lead compound A, we synthesized a new series of dihydropyranopyrazolone 7a-g and dihydro-pyrazolopyranopyrimidin-5-amine 8. The compounds were evaluated for their inhibitory in vitro enzymatic potential against α-amylase, α-glucosidase, acetylcholinesterase & proteinase. Also, the in vitro antioxidant evaluation and cytotoxicity assays were performed for all the final compounds. Interestingly, compound 8 possessed moderate activity against α-amylase (25.38 %) and α-glucosidase (29.37 %) compared to acarbose (75.43 % and 52.79 %, respectively). On the other hand, compound 7f showed a moderate anti-cholinesterase activity (46 ± 0.03 % inhibition) compared to donepezil used as a reference standard drug (67.28 ± 0.61 %). Compound 7d exhibited a moderate anti-arthritic activity (proteinase denaturation (42.21 ± 0.04 %), inhibition of proteinase (38.09 ± 0.04 %)) compared to diclofenac sodium used as a reference (47.93 ± 0.01, 44.96 ± 0.02, respectively). Compound 8 exhibited significant antioxidant activity in TAC assay and increased ABTS scavenging activity. Compounds 7 and derivative 8 exhibited reduced or no toxicity against the normal skin fibroblast thus confirming their safety at least in vitro. The in silico ADMET (absorption, distribution, metabolism, elimination and toxicity) profile of all final compounds implied their acceptability as oral bioavailable drug-likeness property. The anti-hyperglycemic activity was emphasized by the molecular docking of compound 8 showing good interactions in the acarbose binding site of both α-amylase and α-glucosidase enzymes. This study presents the dihydropyrazolopyranopyrimidin-5-amine derivative (compound 8) as a promising scaffold for future modification to design and develop derivatives with increased inhibitory effect against α-amylase and α-glucosidase for the management of type 2 diabetes mellitus (T2DM).

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.

Green solvent selection and extractin protocol for selective recovery of anti-diabetic components from T. crispa

This study systematically explores a green extraction process of T. crispa stems to selectively isolate therapeutic compounds, borapetoside C (BPC) and magnoflorine (MGF), recognized for their anti-diabetic properties. In agreement with Hansen solubility parameters prediction, H2O and EtOH were found to be suitable solvents for extraction of BPC and MGF, respectively, resulting in 33 % and 45 % extractabilities after 60 min. Further investigations demonstrated considerable increase in BPC extractability using 20 % EtOH:H2O mixture at 40 °C, with complete extraction achieved after 60 min. While for MGF, pure-EtOH at 40 °C, was the most suitable solvent, showing the highest selectivity and complete extraction after 100 min. The BPC-rich extract from 20 % EtOH:H2O exhibited higher anti-diabatic activity (IC50 = 0.63 ± 0.03 and 0.72 ± 0.04 mg/mL, respectively, for α-glucosidase and α-amylase enzymes inhibition activity), and considerably lower cytotoxicity to L6 and HepG2 cells, with IC50 = 0.26 ± 0.16 and 0.24 ± 0.02 mg/mL, respectively, compared with the MGF-rich extract obtained with pure-EtOH. Based on these results, a sequential extraction scheme was proposed involving initial pure-EtOH extraction to selectively and completely remove MGF, followed by extraction with a 20 % EtOH:H2O mixture to recover the remaining BPC, which was approximately 80 % of the BPC originally present. The obtained MGF-free BPC-rich extract showed significantly lower cytotoxicity (IC50 = 0.31 ± 0.06 mg/mL against L6 cell) and higher enzyme inhibition activities (IC50 = 0.53 ± 0.32 and 0.52 ± 0.02 mg/mL for α-glucosidase and α-glucosidase enzymes inhibition activity), comparable to acarbose (IC50 = 0.43 ± 0.02 and 0.83 ± 0.03 mg/mL for α-glucosidase and α-glucosidase enzymes inhibition activity), the result that potentially leads to the development of a promising industrial process to harness T. crispa for diabetes prevention and treatment.

Phytochemical Composition, Biological Activity and Molecular Docking Studies of the Endemic Marrubium trachyticum Boiss.

In this study, Marrubium trachyticum Boiss., which is an endemic species for Türkiye, belonging to the genus Marrubium selected from the family Lamiaceae, was examined. The phytochemical composition of hexane and methanol:chloroform (MeOH/CHCl3) (1:1) extracts of M. trachyticum were analyzed quantitatively by GC-MS and LC-MS/MS. Antioxidant activities of the plant extracts and inhibitory activities for various enzymes were determined. In addition, molecular docking studies were performed to understand how the phytochemicals may have an effect on tyrosinase, α-amylase and α-glucosidase enzyme activities. Since there are no studies on the phytochemical composition and bioactivities of M. trachyticum, the data obtained from this study will be recorded for the first time. The chemical composition of the extract of M. trachyticum was determined by GC/MS and the major compound was the dotriacontane with a percentage of 20.23% followed by nonacosane (19.94%). Phenolic compound analysis of MeOH/CHCl3 extract of M. trachyticum plant was carried out quantitatively by LC-MS/MS and rutin (1200 mg kg-1 extract), kaempferol-3-O-glucoside (100.2 mg kg-1extract), hesperidin (75.97 mg kg-1 extract) were found to be the most abundant main compounds in this plant. While no inhibitory effect of M. trachyticum hexane extract was observed on all three enzymes, methanol-chloroform extract showed inhibitory effect on -glycosidase and tyrosinase enzymes. The in vitro and in silico results are evaluated, it is seen that compounds such as rutin, hesperidin and isoquercitrin are more abundant in the extract and have the highest potential to inhibit both enzymes. The present study's results indicate that M. trachyticum is an excellent source of flavonoid components and other bioactive substances that may be responsible for the observed antioxidant and specific enzyme inhibitory effects.

The antihyperglycemic potential of pyrazolobenzothiazine 1, 1-dioxide novel derivative in mice using integrated molecular pharmacological approach

Diabetes Mellitus is a metabolic disease characterized by elevated blood sugar levels caused by inadequate insulin production, which subsequently leads to hyperglycemia. This study was aimed to investigate the antidiabetic potential of pyrazolobenzothiazine derivatives in silico, in vitro, and in vivo. Molecular docking of pyrazolobenzothiazine derivatives was performed against α-glucosidase and α-amylase and compounds were selected based on docking score, bonding interactions and low root mean square deviation (RMSD). Enzyme inhibition assay against α-glucosidase and α-amylase was performed in vitro using p-nitrophenyl-α-D-glucopyranoside (PNPG) and starch substrate. Synthetic compound pyrazolobenzothiazine (S1) exhibited minimal conformational changes during the 100 ns MD simulation run. S1 also revealed effective IC50 values for α-glucosidase (3.91 µM) and α-amylase (8.89 µM) and an enzyme kinetic study showed low ki (− 0.186 µM, − 1.267 µM) and ki′ (− 0.691 µM, − 1.78 µM) values with the competitive type of inhibition for both enzymes α-glucosidase and α-amylase, respectively. Moreover, studies were conducted to check the effect of the synthetic compound in a mouse model. A low necrosis rate was observed in the liver, kidney, and pancreas through histology analysis performed on mice. Compound S1 also exhibited a good biochemical profile with lower sugar level (110–115 mg/dL), increased insulin level (25–30 μM/L), and low level of cholesterol (85 mg/dL) and creatinine (0.6 mg/dL) in blood. The treated mice group also exhibited a low % of glycated haemoglobin (3%). This study concludes that S1 is a new antidiabetic-agent that helps lower blood glucose levels and minimizes the complications associated with type-II diabetes.

Study on Antidiabetic Potential of Sessuvium Portulacastrum Aqueous Extract: An In-Silico and In-Vitro Analysis.

Diabetes mellitus is a persistent metabolic condition marked by elevated blood glucose levels due to compromised insulin secretion or functionality. The search for natural antidiabetic agents has gained attention due to their potential effectiveness and safety profiles. Sessuvium portulacastrum, a coastal plant, has been traditionally used for various medicinal purposes. This study investigates the antidiabetic potential of Sessuvium portulacastrum aqueous extract by analyzing its inhibitory effects on key enzymes involved in carbohydrate metabolism and exploring its molecular interactions with critical target proteins. The aqueous extract of Sessuvium portulacastrum was prepared and used for in vitro analysis. The reduced activity of the extract against α-amylase and α-glucosidase enzymes, crucial in glucose absorption and postprandial hyperglycemia, was assessed. Molecular docking techniques were employed to explore the potential interactions between active compounds in the extract and diabetes-related proteins, including BAX, GSK3β, and CADH. The study revealed significant inhibition of both alpha-amylase and alpha-glucosidase enzymes by Sessuvium portulacastrum aqueous extract, indicating its potential to reduce glucose absorption and postprandial hyperglycemia. Moreover, the molecular docking analysis demonstrated strong binding interactions between active compounds in the extract and key proteins involved in diabetes-related pathways, namely apoptotic pathways, glycogen synthesis, and cell adhesion. The findings of this study highlight the promising antidiabetic potential of Sessuvium portulacastrum aqueous extract. Upcoming research should get an attention on isolating and characterizing the active compounds responsible for these effects on antidiabetic therapies from natural sources.

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.

Safety evaluation of an extension of use of the food enzyme α-glucosidase from the non-genetically modified Aspergillus niger strain AE-TGU.

The food enzyme α-glucosidase (α-d-glucoside glucohydrolase; EC 3.2.1.20) is produced with the non-genetically modified Aspergillus niger strain AE-TGU by Amano Enzyme Inc. A safety evaluation of this food enzyme was made previously, in which EFSA concluded that this food enzyme did not give rise to safety concerns when used in four food manufacturing processes. Subsequently, the applicant requested to extend its use to include three additional processes. In this assessment, EFSA updated the safety evaluation of this food enzyme when used in a total of seven food manufacturing processes. The dietary exposure to the food enzyme-total organic solids (TOS) was estimated to be up to 0.693 mg TOS/kg body weight (bw) per day in European populations. When combined with the no observed adverse effect level previously reported (1062 mg TOS/kg bw per day, the highest dose tested), the Panel derived a margin of exposure of at least 1532. Based on the data provided for the previous evaluation and the revised margin of exposure, the Panel concluded that this food enzyme does not give rise to safety concerns under the revised intended conditions of use.

Exploration of anti-diabetic activity and metabolite profiling of Bruguiera cylindrica (l.) Bl.-in vivo anti-diabetic activity, exploration of molecular mechanism, and network pharmacological analysis.

The Bruguiera cylindrica L. is a mangrove plant that is typically found in coastal areas of Asia, including India. It has been known for its medicinal properties, which have been utilized for generations. For example, in Thailand, it has been used to treat wounds and diarrhoea, while in India, it has been effective in addressing diabetes, ulcers, and other health issues. This particular study sought to investigate the potential of B. cylindrica bark extract in reducing the symptoms of diabetes in rats. In this study, we examined the potential of B. cylindrica bark extract as an inhibitor of α-amylase and α-glucosidase enzymes in vitro. We also evaluated the effects of the extract and Metformin on rats fed high-fat diets and measured their lipid profiles and biochemical parameters. Furthermore, we conducted a network pharmacology analysis to identify proteins and pathways involved in the amelioration of diabetes. Through metabolite profiling, we identified 58 compounds in B. cylindrica hydroalcoholic extract. These compounds include alkaloids, phenolics, flavonoids, and fatty acids. The extract was found to have a dose-dependent inhibition activity against α-amylase and α-glucosidase, with IC50 values similar to acarbose. In rats, oral administration of 200-400 mg/kg of B. cylindrica led to reduced blood glucose levels and normalized serum biochemical parameters. Bruguiera cylindrica bark may reduce blood sugar levels in rats with diabetes. The study found metabolites that interact with protein targets associated with different types of diabetes.

Indolyl imine compounds as multi-target agents; synthesis, antidiabetic, anticholinesterase, antioxidant activities and molecular modeling

A new range of indolyl imine system 3d-l has been successfully prepared from 4,6-dimethoxy-2,3-diphenyl-indole-7-carbaldehyde 2a and 4,6-dimethoxy-3-aryl-indole-7-carbaldehyde 2b-cvia Schiff base reaction. The structure of targeted compounds was confirmed by 1H and 13C NMR, FT-IR, mass spectrometry and single crystal X-ray diffraction techniques. The indolyl imine derivatives were also subjected to in vitro antidiabetic activities employing α-glucosidase and α-amylase enzymes. In terms of antidiabetic investigation, the α-glucosidase enzyme was found to be potential target due to the comparable inhibition concentrations with the standard acarbose and the compound 3e exhibited better potency than the standard. The anticholinesterase potency of the compounds was investigated towards the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. The compounds displayed moderate efficiency against the BChE enzyme with the best inhibition concentration of 30.48 μM by the compound 3h. The antioxidant properties of final compounds were determined by DPPH radical scavenging, ABTS Cation Radical Decolarization and CUPRAC Cupric Reducing Antioxidant Capacity assay methods. The ABTS cation scavenging assay provided the best responses for the compounds and the candidates 3k and 3l were determined as promising targets for the antioxidant activity. Plausible binding mode and interaction of ligands with the selected enzyme have been studied by molecular docking, supporting the experimental results. In silico ADME showed high drug likeness of the synthesized compounds.

Metabolomics combined with chemometric analysis to identify α-glucosidase inhibitors in Phaleria macrocarpa fruit extracts and its molecular docking simulation

Phaleria macrocarpa is a medicinal plant widely available in Malaysia. The plant parts have been traditionally used as an antidiabetic remedy. This study aimed to identify the putative inhibitors of the α-glucosidase enzyme from P. macrocarpa using a gas chromatography-mass spectrometry (GC–MS)-based metabolomics approach and further subjected them to in silico molecular docking analysis to elucidate the possible mechanism of action. This study assessed the inhibitory potential of P. macrocarpa fruit extracts (aqueous, 20 %, 40 %, 60 %, 80 %, and 100 % ethanol) against the α-glucosidase enzyme using GC–MS and chemometric analysis. Orthogonal partial least squares (OPLS) combined with GC–MS analysis were applied to correlate the inhibition of enzyme activity to the metabolites profile of P. macrocarpa. All the potential inhibitors identified were further docked to the yeast (Saccharomyces cerevisiae) protein crystal structure (PDB3A4A). The generated score scatter plot of OPLS showed a recognizable separation of all the extracts into six different clusters. GC–MS, incorporated with multivariate data analysis techniques, was used to identify significant chemical markers. Methyl α-d-glucopyranoside, squalene, palmitic acid, myo-inositol and isoquinoline metabolites were identified as putative inhibitors against α-glucosidase activity from P. macrocarpa. In conclusion, the GC–MS-based metabolomics approach identified potential chemical markers of P. macrocarpa that could be utilized in the development of herbal based medicine.

Ultrasonication-assisted optimization of pterostilbene extraction from Pterocarpus santalinus heartwood using response surface methodology

The present investigation established optimal conditions for ultrasonication-assisted extraction concerning yield and pterostilbene content using response surface methodology (RSM) based on Box-Behnken design (BBD) from the heartwood of Pterocarpus santalinus originating from different geographical locations (sample AP and WB). The influence of extraction temperature (X1: 30–50 °C), sonication time (X2: 15–45 min), and solvent/biomass ratio (X3: 20–60) were used as independent input variables resulting in the optimal conditions X1: 42.18, X2: 15.54, X3: 31.58 (sample AP) and X1: 30.00, X2: 31.38, X3: 20.00 (sample WB). Experimentally obtained values of yield 168.375 mg and 20.1 mg and AUC 498354 and 695295, respectively, for sample AP and WB, were in close agreement with those predicted by the RSM-BBD model. Additionally, the samples displayed the potential to inhibit the enzyme α-glucosidase.

Evaluation of Anti--amylase and Anti--glucosidase Activity of Canna x Generalis L.H Bailey & E.Z Bailey Rhizome

Canna x generalis L.H Bailey & E.Z Bailey (CG) has been used as folk medicine to treat different diseases. However, scientific information about the pharmacological effects and chemical composition of this plant is still very limited. This study aims to evaluate for the first time the α-amylase and α-glucosidase inhibitory activity of CG rhizome extracts. The rhizome part of CG was extracted with ethanol and then fractionated with n-hexane, ethyl acetate, and water. The total extract and fractions were evaluated for their inhibitory effects on α-amylase and α-glucosidase enzymes in vitro. The results showed that the ethyl acetate fraction had the strongest inhibitory activity against α-amylase and α-glucosidase with IC50 values of 53.19 ± 2.79 and 95.83 ± 6.26 µg/mL, respectively. Therefore, the rhizome part of the CG plant, especially the ethyl acetate fraction, is a potential natural source for searching for active ingredients to prevent and treat diabetes.
 
 

Screening In Silico Alpha-amylase and Alpha-glucosidase Inhibitory Activity of Flavonoid Compounds for the Treatment of Type 2 Diabetes

Diabetes mellitus (diabetes) is a chronic disease associated with metabolic disorders and hyperglycemia. α-glucosidase and α-amylase, which play an important role in the hydrolysis of starch and carbohydrates, are enzymes. They are related to the increase and decrease in blood glucose levels. Flavonoids are a common group of natural compounds that have been shown to have many beneficial health effects. This study used molecular docking methods and drug-like criteria, predicting pharmacokinetics-toxicity (ADMET) to screen and evaluate potential flavonoid compounds in the treatment of type 2 diabetes. After screening the compounds, we obtained 46 compounds with lower binding energies than the positive controls, which are acarbose. Using Lipinski's rule of five, we evaluated the drug-likeness of the compounds and identified 12 compounds that met the criteria. Then, continuing to analyze according to pharmacokinetic and toxicological parameters (ADMET), we obtained 3 compounds including Galangin, Maackiain, and Corylin, that have the potential to be developed into drugs when showing the ability to simultaneously inhibit both enzymes α-glucosidase and α-amylase have positive properties: binding energy is lower than the control, creates many interactions with target proteins in the active site, has drug-like properties, relatively good pharmacokinetic properties and low toxicity. Therefore, further in vitro and in vivo studies are needed to develop these potential compounds into drugs for the treatment of type 2 diabetes.
 
 
 

Synthesis, biological activities, and molecular docking studies of triazolo[4,3-b]triazine derivatives as a novel class of α-glucosidase and α-amylase inhibitors.

In diabetes mellitus, amylase and glucosidase enzymes are the primary triggers. The main function of these enzymes is to break macromolecules into simple sugar units, which directly affect blood sugar levels by increasing blood permeability. To overcome this metabolic effect, there is a need for a potent and effective inhibitor capable of suppressing the enzymatic conversion of sugar macromolecules into their smaller units. Herein, we reported the discovery of a series of substituted triazolo[4,3-b][1,2,4]triazine derivatives as α-glucosidase and α-amylase inhibitors. All target compounds demonstrated significant inhibitory activities against α-glucosidase and α-amylase enzymes compared with acarbose as the positive control. The most potent compound 10k, 2-[(6-phenyl-[1,2,4]triazolo[4,3-b][1,2,4]triazin-3-yl)thio]-N-[4-(trifluoromethyl)phenyl]acetamide, demonstrated IC50 values of 31.87 and 24.64 nM against α-glucosidase and α-amylase enzymes, respectively. To study their mechanism of action, kinetic studies were also done, which determined the mode of inhibition of both enzymes. Molecular docking was used to confirm the binding interactions of the most active compounds.