Α-glucosidase Enzyme Inhibition Research Articles

Two tetrahydroxyterpenoids and a flavonoid from Xylocarpus moluccensis M.Roem. and their α-glucosidase inhibitory and antioxidant capacity

Context: Scientific verification of the anti-hyperglycemic potential of Kayu sarampa (Xylocarpus moluccensis), which is popularly used for diabetic medication in North Sulawesi, Indonesia, is strongly important to conduct to avoid inappropriate medication that might cause worse conditions. Aims: To investigate the anti-hyperglycemic potential of X. moluccensis stem bark ethyl acetate extract and isolated compounds through the α-glucosidase enzyme inhibitory and antioxidant capacity determination. Methods: The active compound was isolated from ethyl acetate extract of X. moluccensis stem bark. The structures of those compounds were elucidated by infrared spectroscopy, liquid chromatography–mass spectrometry, and nuclear magnetic resonance spectroscopies. To discover the anti-hyperglycemic potency, α-glucosidase enzyme inhibition assay, antioxidant assay (DPPH and FRAP), and in silico study were performed. Results: Three isolated compounds were obtained and characterized as two tetrahydroxyterpenoids compounds, namely xyloccensin E (1) and ruageanin D (2), and one flavonoid compound, namely 3,5,7,3ʹ,4ʹ-pentahidroxyflavan (catechin) (3). Compounds 1 and 3 inhibited the α-glucosidase enzyme with IC50 values of 118.60 and 55.19 µg/mL, respectively, with a competitive inhibition mechanism. This is also in line with in silico findings, and both compounds showed good binding affinity of α-glucosidase protein, which indicated their anti-hyperglycemic activity potential by inhibiting α-glucosidase enzyme. Moreover, compounds 1 and 3 showed antioxidant capacity through the DPPH method with an IC50 value of 54.69 and 2.87 µg/mL. In addition, 100 µg/mL of compounds 1 and 3 also exhibited antioxidant capacity through the FRAP method with values of 66.35 and 213.82 µmol Fe2+/g, respectively. Conclusions: The X. moluccensis stem bark ethyl acetate extract, and isolated compounds exhibit α-glucosidase enzyme inhibitory activity and antioxidant capacity, which confirms its potency as an alternative medication for hyperglycemia issues.

Anti-diabetic potential of Chamaerops humilis L. aerial parts: Phenolic compounds with α-amylase and α-glucosidase inhibitory activates in-vitro, in-vivo and in-silico studies

Five compounds were isolated from the aerial parts of Chamaerops humilis L. and characterized as tricin-7-rutinoside (1), tricin (2), dihydrotricin (3) diasteroisomer of tricin 4′-O(erythro-β-guaiacyl glyceryl) ether (salcolin A)(4a), tricin-4′-O-(threo-β-guaiacyl glyceryl) ether (salcolin B) (4b) and (-)-(5s, 6s)-5,6-dihydro-3,8,10-trihydroxy-5-(4-hydroxy-3-methoxyphenyl)-6-hydroxymethyl-2,4-dimethoxy 7H benzo [e] xanthen-7-one (5). Their structures were elucidated by comparing their spectral data with those reported in the literature. To the best of our knowledge, compounds (3-5) were reported here for the first time from Chamaerops humilis. The methanolic extract of Chamaerops humilis (CHME) and the five isolated compounds were studied for its anti-diabetic effect using in vitro α-glucosidase and α-amylase inhibitory assay that showed a significant activity. The toxicological study indicated that CHME was safe up to 5000 mg/kg bw. Two doses were selected for the in vivo study (800 and 1600 mg/kg bw) and orally administered to high fat diet/streptozotocin-induced diabetic rats for 10 consecutive days. The results revealed that the CHME improved the blood glucose levels in a dose dependent manner, the dose 1600 mg/kg showed the best results dependently along the period of the experiment. CHME and the five isolated compounds were evaluated in silico for their anti-diabetic effect. The anti-inflammatory effect of CHME (1600 mg/kg bw) was proved by significant downregulation of expression for interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-1 (MMP-1) genes. In conclusion, CHME and its constituents may be a potential hypoglycemic agent working through the anti-inflammatory and enzyme inhibitory pathways. The docking studies demonstrated that compounds Tricin7-rutinoside and Salcolin isomers had promising binding energies of -9.10 kcal/mol and -8.70 kcal/mol, respectively, against α-amylase. These binding energies were superior to that of acarbose, which had a binding energy of -7.60 kcal/mol. In addition, docking analysis provided promising results for the inhibition of α-glucosidase by Tricin7-rutinoside and Dihydrotricin with binding affinity -7.9 kcal/mol and -7.9 kcal/mol, respectively while the binding affinity of acarbose is -6.40 kcal/mol. Overall, the methanolic extract from Chamaerops humilis exhibited good in silico of α-amylase and α-glucosidase enzyme inhibition potential. These findings suggest that these compounds may have potential as anti-diabetic agents, with further research needed to verify their efficacy and safety.

Antiglycating Effects of Spirulina platensis Aqueous Extract on Glucose-Induced Glycation of Bovine Serum Albumin.

Glucose, the predominant carbohydrate in the human body, initiates nonenzymatic reactions in hyperglycemia, potentially leading to adverse biochemical interactions. This study investigates the interaction between glucose and Bovine Serum Albumin (BSA), along with the protective effects of Spirulina platensis PCC 7345 aqueous extract. Phycobiliproteins (phycocyanin, phycoerythrin, and allophycocyanin) in the extract were quantified using spectrophotometry. The extract's anti-glycation potential was assessed by analyzing its effects on albumin glycation, fluorescent advanced glycation end products (AGEs), thiol group oxidation, and β-amyloid structure generation. Additionally, its antidiabetic potential was evaluated by measuring α-amylase and α-glucosidase enzyme inhibition. Results indicate that the Spirulina extract significantly mitigated ketoamine levels, fluorescence, and protein-carbonyl production induced by glucose, demonstrating a 67.81% suppression of AGE formation after 28 days. Moreover, it effectively inhibited amyloid formation in BSA cross-linkages. These findings suggest the potential of S. platensis as an anti-glycation and antidiabetic agent, supporting its consideration for dietary inclusion to manage diabetes and associated complications.

Characterisation of physicochemical properties, anti-hyperglycaemic effects, and probiotic potentials in fermented pumpkin drink utilising Lactobacillus mali isolated from water kefir

Pumpkin has been reported to be a good probiotic delivery vehicle, but it has a short shelf life, is susceptible to enzymatic browning, and prone to microbial spoilage. Pumpkin could be transformed into a value-added beverage through the fermentation by LAB. In the present work, the probiotic viability, physicochemical, antioxidative, antihyperglycemic, and sensory properties of Lactobacillus mali-fermented pumpkin drink (FPD) during eight weeks of refrigerated storage at 4°C were investigated. There were significant reductions (p < 0.05) in colour, pH, texture characteristics, and antioxidant properties after four weeks of storage. FPD exhibited total phenolic content ranging from 83.75 to 90.75 mg GAE/mL, total flavonoid content ranging from 47.01 to 50.01 mg QE/mL, FRAP reducing power ranging from 160.76 to 169.76 µmol Trolox equivalent/mL, and DPPH scavenging activity ranging from 52 to 54.56% during storage. FPD's total soluble solids decreased (p < 0.05) from 0.60 to 0.02 °Brix, while concentrations of ethanol (0.62 to 1.2%, v/v), lactic acid (0.03 to 0.11 g/L), and acetic acid (0.02 to 0.18 g/L) significantly increased (p < 0.05) over eight weeks of storage. L. mali strain within FPD maintained its viability (p > 0.05) under simulated gastrointestinal conditions, with 8 - 9.1 log CFU/mL for 28 days at 4°C. FPD retained up to 90% α-glucosidase enzyme inhibition throughout the 28 days storage period. Sensory evaluation showed that FPD's attributes remained unchanged (p > 0.05) during the initial four weeks of storage, with an overall acceptability score ranging from 6.56 to 6.88. In conclusion, FPD remained stable in terms of physicochemical, antioxidative, and sensory properties, as well as probiotic viability and anti-hyperglycaemic effects during 28 days of refrigerated storage. This highlights FPD’s potential as a functional beverage, presenting an innovative method to utilise pumpkin as an effective probiotic carrier.

Vitis vinifera L. seed standardized extract; a promising therapeutic against metabolic syndrome induced by high-fat/high-carbohydrate diet and streptozotocin in rats

Metabolic syndrome (MetS) is a group of abnormal disorders; hypertension, glucose intolerance, dyslipidemia, proinflammatory, and prothrombotic states, affecting approximately 14 % of the world's population. The potential of grape seeds extract (GSE) supplementation to improve the metabolic disturbances and their related conditions like obesity, type 2 diabetes, and nonalcoholic fatty liver disease was investigated in this study. In-vitro metabolic syndrome assays were investigated through α-amylase, α-glucosidase, lipase, lipoxygenase (LOX), cyclooxygenases (COX-1 and COX-2), renin and angiotensin converting enzyme (ACE) inhibition assays. Additionally, in-vivo rat model of high-fat-high-carbohydrate diet (HFD)-induced MetS was established, where metformin (MT) (200 mg/kg) was used as a reference drug and GSE was given at 100 and 200 mg/kg by oral gavage. GSE was standardized using HPLC analysis for the major reported compound; catechin which should be ≥ 160.76 ± 5.52 μg/mL. Total phenolic content of GSE was 21.12±0.61 µg gallic acid equivalent/1 mg extract and total flavonoid content was 23.81±0.64 µg rutin equivalent/1 mg extract. In-vitro assays revealed the potential of GSE to manage the metabolic syndrome, besides its strong antioxidant capacity. Treatment with GSE (100 mg/kg and 200 mg/kg) markedly (P < 0.05) controlled the weight gain, improved the metabolic pathways (total glucose, cholesterol, triglycerides, AST, and ALT), oxidative stress parameters (MDA, GSH, and catalase) and inflammatory biomarkers in HFD fed rats. GSE downregulated the expression of insulin resistance gene (IR) and some inflammatory related genes (TNF-α and NF-κB), additionally it improved the pathological features of metabolic conditions and upgraded the expression of Nrf2 compared to HFD group. The superior effects were owned to the high dose of GSE, 200 mg/kg b.wt. (P < 0.05, P < 0.001). All results sustenance the beneficial effects of the standardized GSE in the management of metabolic syndrome.

Fatty Acid Composition, Antioxidant, and Enzyme Inhibition Activities of Cachrys Crassiloba (Boiss.) Meikle Fruit and Leaf Extracts

The genus Cachrys L. (Apiaceae) is distributed in the Mediterranean region and contains 11 species. C. crassiloba (Boiss.) Meikle is a species that grows in Southwest and Western Anatolia. Considering the literature studies, there were not enough studies on C. crassiloba. In this study, fatty acid composition, total phenol/flavonoid contents, antioxidant and acetyl-butrylcholinesterase, tyrosinase, and α-glucosidase enzyme inhibition activities of n-hexane and ethanol extracts prepared from C. crassiloba fruits and leaves were investigated by spectrophotometric methods at different concentrations. When the results were evaluated, it was found that the hexane extract of C. crassiloba leaf (123.92 ± 4.62 GA mg/g extract) had the highest total phenol content, while the ethanol extract of C. crassiloba fruit (134.38 ± 0.98 QE mg/g extract) had the highest flavonoid content. C. crassiloba hexane and ethanol leaf extracts (IC50= 8.04 ± 1.31 µg/mL; 10.30 ± 3.15 µg/mL) showed good antioxidant activity com-pared to the ascorbic acid (IC50= 14.59 ± 1.96 µg/mL) in DPPH assay. C. crassiloba leaf ethanol extract (IC50= 17.38 ± 5.02 µg/mL) has the highest ABTS scavenging activity. C. crassiloba extracts have mod-erate cholinesterase inhibitory activity. C. crassiloba leaf ethanol extract (IC50= 196.65 ± 1.94 µg/mL) has good tyrosinase enzyme inhibition activity. C. crassiloba leaf hexane extract (36.35% ± 1.13) was found to have significant inhibitory activity against α-glucosidase. In conclusion, besides its antioxidant activity, C. crassiloba may be effective against neurodegenerative diseases and skin disorders such as hyperpigmentation and diabetes mellitus, but further phytochemical analysis studies are required.

A network pharmacology approach with experimental validation to discover protective mechanism of poly herbal extract on diabetes mellitus

ObjectivePolyherbal extracts (PHE) contain six traditional medicinal plants, and the efficacy of the medicinal plants used in the preparation of this PHE has been confirmed for the treatment of diseases like diabetes mellitus (DM). The aim of this study was to evaluate the efficacy and therapeutic mechanism of PHE through a network pharmacology approach to reveal the protective mechanism of Alpha-Tocospiro A (ATA) present in PHE on DM with experimental validation. MethodsIn this study, Lipinski's rule (Swiss ADME) and drug-likeness score (MolSoft's) web pages were used to confirm the drug-likeness of identified constituents in PHE. Swiss Target Prediction (STP) genes were found for ATA-related genes. The DisGeNet database was used to screen genes associated with DM. String created a network diagram of the interactions between the ATA and DM genes. Top-scoring genes from the string network through CytoNCA plugged into Cytoscape 3.8.2 were selected as hub genes. In addition, the ShinyGO database is used to predict GO and KEGG pathway enrichment analyses. ResultsA total of 675 and 105 therapeutic genes (STP) were associated with all bioactive compounds and ATA in the PHE screen, respectively. Additionally, a maximum of 2,803 DM-related genes (DisGeNet) were observed. Further, in the analysis, 331, 57 potential (intersecting) genes were identified in the correlation between the target genes of all compounds and ATA, respectively, of PHE and the target genes of DM. The identified hub gene “TNF” for both ATA and PHE was found to be precisely strengthened in 49 pathways, along with 14 signaling pathways out of more than 100 enriched KEGG pathways. This study predicted that ATA activates PI3K/Akt and MAPK pathways enriched with TNF by phosphorylating the insulin receptor (IR) β-subunit. The anti-diabetic activity of PHE was found to be good and primarily confirmed by in vitro α-glucosidase enzyme inhibition activity. ConclusionThe anti-diabetic activity of PHE was found to be effective and was confirmed by the enzyme inhibition activity in the primary study. This study predicted that ATA is a novel drug molecule in PHE that has a targeted mechanism of action and therapeutic effect on DM.

Phytochemical analyses by LC-HRMS, FTIR spectral analysis, antioxidant, antidiabetic and antityrosinase activity of Crataegus orientalis Pall. ex M. Bieb fruit extracted with various solvents.

Crataegus orientalis Pall. ex M. Bieb fruit (COPMB) is extensively used as a source of various products in the medicinal-aromatic field and holds the potential for erosion control, ornamental purposes, food source, and economic benefits for forest villagers from its fruits. This study aims to determine the chemical components and biological activities of extracts prepared from COPMB using different solvents. The present work was designed to define the antioxidant activity [phosphomolybdenum (total antioxidant capacity), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), cupric ion-reducing antioxidant capacity (CUPRAC) and metal chelating activity (MCA)], phytochemical screening analysis, enzyme inhibitor (α-amylase, α-glucosidase and tyrosinase) potential, and liquid chromatography-high resolution mass spectrometry (LC-HRMS) secondary metabolite profiling in different extracts of COPMB. The results of LC-HRMS revealed that fumaric acid was the main phenolic compound in all extracts. Among the extracts, ethyl acetate extract has the highest phytochemical and antioxidant properties [total phenolic content (TPC): 32.5 mg GAE/g, total flavonoid content (TFC): 12.2 mg QE/g, ABTS: 213.0 mg TE/g; CUPRAC: 126.0 mg TE/g, MCA: 145.0 mg EDTA/g; FRAP: 122.8 mg TE/g; TAC: 2.8 mmol TE/g]. Ethyl acetate and methanol extracts are more effective in α-amylase (0.27 ± 0.01 mg/mL; 0.12 ± 0.00 mg/mL), α-glucosidase (0.63 ± 0.02 mg/mL; 0.77 ± 0.02 mg/mL) and tyrosinase (0.03 ± 0.00 mg/mL; 0.03 ± 0.00 mg/mL) enzyme inhibition potentials compared to standard acarbose (0.75 ± 0.02 mg/mL for α-amylase; 1.11 ± 0.03 mg/mL for α-glucosidase) and kojic acid (0.04 ± 0.00 mg/mL). The findings from this study suggest that COPMB could serve as a valuable source of natural agents for the food and pharmaceutical industry. © 2024 Society of Chemical Industry.

A Review on the Development of Novel Heterocycles as α-Glucosidase Inhibitors for the Treatment of Type-2 Diabetes Mellitus.

One of the most effective therapeutic decencies in the treatment of Type 2 Diabetes Mellitus is the inhibition of α-glucosidase enzyme, which is present at the brush border of the intestine and plays an important role in carbohydrate digestion to form mono-, di-, and polysaccharides. Acarbose, Voglibose, Miglitol, and Erniglitate have been well-known α-glucosidase inhibitors in science since 1990. However, the long synthetic route and side effects of these inhibitors forced the researchers to move their focus to innovate simple and small heterocyclic scaffolds that work as excellent α-glucosidase inhibitors. Moreover, they are also effective against the postprandial hyperglycemic condition in Type 2 Diabetes Mellitus. In this aspect, this review summarizes recent progress in the discovery and development of heterocyclic molecules that have been appraised to show outstanding inhibition of α-glucosidase to yield positive effects against diabetes.

Antibacterial and Carbohydrate Digestive Enzyme Inhibitory Effects of Native Plants Used for Medicinal and Culinary Purposes in Cyprus

Natural products are an inexhaustive reservoir of bioactive compounds with diverse effects protecting human health as components of nutrition and as active substances of drugs. The objective of the present study was to evaluate the bactericidal and carbohydrate digestive enzyme inhibitory activity of twelve native plants from Cyprus, that are consumed for medicinal and/ or culinary purposes. Each plant was sequentially extracted with solvents of increasing polarity, from non-polar to polar solvents. At first, the total phenolic (TPC) and flavonoid (TFC) content of the extracts were determined. The bactericidal potential of plant extracts was tested against six bacteria using the broth microdilution method. Furthermore, their inhibitory effects on digestive enzymes, namely α-glucosidase and α-amylase, were also determined. Results demonstrated a substantial diversity in TPC (2.3-483.5 mg gallic acid equivalent g−1) and TFC (4.1-394.6 mg catechin equivalent g−1) of the plant extracts; a great impact of solvent was found. Furthermore, potent antibacterial activity (minimum bactericidal concentration ≤ 500 µg ml−1) of capper, mountain oregano, rosemary, silver thistle, and vine leaf extracts against Gram-positive bacteria was determined. Regarding carbohydrate digestive enzyme inhibitory effects, the inhibition of α-glucosidase enzyme is higher than 80%, when rosemary, silver thistle, and vine leaf extracts are used at a concentration of 500 µg g−1. Overall, the present study describes the antibacterial and inhibitory effect against carbohydrate digestive enzymes of unstudied plant species or known plants from the unexplored island of Cyprus. It provides valuable data for the nutraceutical value of native edible plants as well as assesses these plants as potential sources of antibacterial and carbohydrate digestive enzyme inhibitory agents for drug discovery.

The Effectiveness of Flavonoids in Pigeon Pea (Cajanus cajan) as Inhibitors of α-Glucosidase Enzyme in Anti-diabetes

Diabetes mellitus is a metabolic disease characterized by hyperglycemia, due to relative and absolute insulin deficiency of the body. Acarbose is a drug that can be used to treat diabetes mellitus, especially type II diabetes mellitus. Type II diabetes mellitus is an endocrine disease that causes 95 % of deaths worldwide. Gude bean extract (Cajanus cajan) is one alternative to the use of natural anti-diabetic medicine, containing saponins, flavonoids, phenolics, and tannins. Flavonoids are antioxidant compounds that have a hypoglycemia effect in people with diabetes mellitus. This study aimed to test the inhibitory activity of alpha-glucosidase enzyme from gude bean extract. The enzyme α-glucosidase activity was quantified by measuring the quantity of para-nitrophenol generated at a wavelength of 405 nm. The inhibitory power of the α-glucosidase enzyme was seen from the IC50 value. Gude Bean Extract has the ability to inhibit the enzyme α-glucosidase resulting in an IC50 value of 69.67 ppm strong level activity. Gude Bean Extract has the ability to inhibit the enzyme α-glucosidase resulting in an IC50 value of 69.67 ppm with a strong strength level

α-Glucosidase Inhibitory Activity and Cytotoxicity of CeO2 Nanoparticles Fabricated Using a Mixture of Different Cerium Precursors.

A mixture of three distinct cerium precursors (Ce(NO3)3·6H2O, CeCl3·7H2O, and Ce(CH3COO)3·H2O) was used to prepare cerium oxide nanoparticles (CeO2 NPs) in a polyol-mediated synthesis. Different ratios of diethylene glycol (DEG) and H2O were utilized in the synthesis. The properties of the synthesized CeO2 NPs, such as structural and morphological properties, were investigated to observe the effect of the mixed cerium precursors. Crystallite sizes of 7-8 nm were obtained for all samples, and all synthesized samples were confirmed to be in the cubic phase. The average particle sizes of the spherical CeO2 were between 9 and 13 nm. The successful synthesis of CeO2 can also be confirmed via the vibrational band of Ce-O from the FTIR. Antidiabetic properties of the synthesized CeO2 NPs were investigated using α-glucosidase enzyme inhibition assay, and the concentration of the synthesized CeO2 NPs was varied in the study. The biocompatibility properties of the synthesized CeO2 NPs were investigated via cytotoxicity tests, and it was found that all synthesized materials showed no cytotoxic properties at lower concentrations (62.5-125 μg/mL).

Multifunctional apple seed protein hydrolysates: Impact of enzymolysis on the biochemical, techno-functional and in vitro α-glucosidase, pancreatic lipase and angiotensin-converting enzyme inhibition activities

The work was designed to assess the amelioration effect of papain hydrolysis on the biochemical, techno-functional, and biological properties of apple seed protein isolate (API) after 0–90 min of hydrolysis. Hydrolysis significantly enhanced the nutritional value (protein content ˃ 90 %) while decreasing the average particle size. With increasing hydrolysis time, FTIR analysis revealed a transition from α-helix to β-turn structure, indicating the unfolding of protein structure. This structural alteration positively influenced the functional characteristics, with samples hydrolyzed for 90 min exhibiting excellent solubility, higher water and oil absorption capacity, foaming capacity, and increased emulsifying activity index. Moreover, samples hydrolyzed for 90 min displayed the highest α-glucosidase (29.62–57.43 %), pancreatic lipase inhibition (12.87–31.08 %), and ACE inhibition (25.32–62.70 %) activity. Interestingly, the inhibiting ability of protein hydrolysates against α-glucosidase and ACE was more effective than pancreatic lipase, suggesting their usefulness as a functional ingredient, particularly in type II diabetes and hypertension management.

Design, synthesis, in-vitro biological screening and in-silico studies of 2-thioxodihydropyrimidinone based new aminomethylene scaffolds

A successful attempt was made to avail ten new 5-anilinoaminomethylene substituted 2-thioxodihydropyrimidinones (H1–H10) via one-pot three-component reaction of 1,3‑diethyl-2-thiobarbituric acid, triethyl orthoformate and respective substituted anilines in good to excellent yields (84–92 %). All the synthesized compounds were fully characterized by detailed spectroscopic techniques, like UV–Vis., IR, NMR and HRMS after purification. In-vitro investigations including DPPH free radical scavenging ability, acetyl- and butyrylcholinesterases inhibition, α-glucosidase inhibition, phytotoxicity and insecticidal activities of the synthesized compounds were performed, and very promising results were obtained. Compounds H6-H10 showed amazing potency as DPPH free radical scavengers with IC50 values of 0.88 ± 0.053, 0.54 ± 0.164, 1.22 ± 0.07, 0.20 ± 0.055 and 1.58 ± 0.123 mg/mL, respectively, better than reference compound ascorbic acid (IC50 1.79 ± 0.045 mg/mL). Similarly, compounds H2 and H4 declared greater inhibition of α-glucosidase enzyme with IC50 of 319.46 ± 1.45 and 263.57 ± 1.34 µM respectively, as compared to the reference compound acarbose (IC50 375.82 ± 1.76 µM). The bioinformatics study of the synthesized compounds comprised drug likeness, metabolites prediction, molecular docking analyses against eight selected target substrates. Docking analysis showed that the binding energy values of compounds H2, H3 and H5 were –11.25, –10.91 and –12.30 Kcal/mol respectively, which are better than standard drug diltiazem possessing –10.79 Kcal/mol against P450 CYP 3A4. Finally, the rat acute toxicities were estimated through four different routes of administration and the results reflect promising behaviors of the test compounds in their toxicity evaluation. Based on the encouraging results in all these analyses, our target compounds may be used as hits for future investigation towards drug discovery.

The inhibition of α-Glucosidase enzyme activity from Standardised Ethanol Extract of Abelmoschus manihot (L.) Medik Leaves

People have long utilised the leaves of the red gedi, Abelmoschus manihot (L.) Medik is an anti-diabetic medication. The study’s objectives were to classify chemical constituent groups, assess extract quality, and evaluate the activity of α-glucosidase enzyme inhibitors. The extraction method employed kinetic maceration with a 70% ethanol solvent, identification was accomplished through phytochemical screening, a quality determination was based on both specific and non-specific parameters, and α-glucosidase inhibition was used in an in vitro antidiabetic activity test. Flavonoids, alkaloids, saponins, steroids, and triterpenoids were found in the phytochemical screening test results. The results of the quality parameter test obtained viscous extract, blackish green color, 70.58% water soluble extract, 49.46% ethanol soluble extract, 7.82% loss on drying, 4.19% water content, total ash content 6.97%, acid insoluble ash content 0.60%, water-soluble ash content 5.64%, residual solvent 0.76%, heavy metal content Pb 1.35 mg/kg, Cd 0.06 mg/kg, plate number total ≤10 colonies/g, yeast plate number 20.1995 colonies/g and total flavonoid content 1.20%. The α-glucosidase enzyme inhibitory activity test from the extract and acarbose (positive controls) obtained IC50 values of 81.84 μg/mL and 42.6 μg/mL, respectively. In conclusion, the α-glucosidase enzyme may be inhibited by the ethanolic extract of A. manihot (L.) Medik leaves.

Hypoglycemic activity of Syzygium cumini (L.) Skeels seed extracts: an approach to in vitro, in vivo, and in silico studies

This research is carried out to explore the hypoglycemic activity of Syzygium cumini seed extracts by in vitro, in vivo, and in silico methods. For in vitro studies the α-amylase and α-glucosidase enzyme inhibition assays were employed. For in vivo studies 30 alloxan induced Wistar rats were used. They were orally administered with glibenclamide and low/high dose of the extracts and were monitored regularly for the change in blood glucose levels for about 28 days. The in silico molecular docking was conducted to evaluate the binding interaction of 1,2,3-Benzenetriol with human pancreatic α-amylase and α-glucosidase. It was found that all the extracts were able to inhibit the α-amylase and α-glucosidase enzymes. Among which the acetone extract showed greater inhibition with 72.52 ± 0.51% and 63.02 ± 0.73% for both the enzymes, respectively. There was significant (p < 0.05) reduction in blood glucose levels in the rats administered with glibenclamide and extracts. In silico docking results revealed that the compound 1,2,3-Benzenetriol exhibited the highest binding affinity for human pancreatic α-amylase with binding energy −7.7 kcal/mol. Thus suggesting the utilization of S. cumini seeds in the management of diabetes mellitus. Communicated by Ramaswamy H. Sarma

Total phenolic and flavonoid contents of Aphanamixis polystachya (Wall.) R.Parker leaf extract and its potential as antioxidant and inhibitor of α-glucosidase

Indonesia is one of the countries with the highest plant diversity in the world, including the Aphanamixis genus, and they use the plants in this genus as traditional medicine. The genus Aphanamixis has a wide variety of compounds with different activities, such as insecticidal, leishmanicidal, antimicrobial, anticancer, cytotoxic against some cancer cells, and antioxidant The focus of this research is to find out about the anti-oxidant, anti-diabetic, and anti-bacterial activities of Aphanamixis polystachya leaf extract from the Bali Botanical Garden plant collection. The antioxidant activity assay was carried out by scavenging the free radical 1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenyl ethylamino) propane hydrochloride (DPPH). The antidiabetic assay was carried out by inhibiting the activity of the α-glucosidas eenzyme, while the antibacterial test was carried out by the agar diffusion method. Based on the data generated in this study, the active ingredients of A. polystachya leaf extracts have high potency as antioxidants and α-glucosidase enzyme inhibitors, but the extract was not effective in inhibiting bacterial growth.

Synthesis, density functional theory and kinetic studies of aminopyridine based α-glucosidase inhibitors.

Aims: The current study aimed to develop new thiourea derivatives as potential α-glucosidase inhibitors for the management of hyperglycemia in patients of Type 2 diabetes, with a focus on identifying safer and more effective antidiabetic agents. Materials & methods: New thiourea derivatives (1-16) were synthesized through single-step chemical transformation and evaluated for in vitro α-glucosidase inhibition. Kinetic studies identified the mode of inhibition, free energy and type of interactions were analyzed through density functional theory and molecular docking. Results & conclusion: Compound 5 was identified as the most potent, noncompetitiveand noncytotoxic inhibitor of α-glucosidase enzyme with half-maximal inhibitory concentration of 24.62±0.94μM. Computational studies reinforce experimental results, demonstrating significant enzyme interactions via hydrophobic and π-π stacking forces.

Lactic acid fermentation of guava juice: Evaluation of nutritional and bioactive properties, enzyme (α-amylase, α-glucosidase, and angiotensin-converting enzyme) inhibition abilities, and anti-inflammatory activities.

In the present research, the impact of fermentation with two strains of Lactiplantibacillus plantarum subsp. plantarum (PTCC 1896 and PTCC 1745) on physicochemical properties, antioxidant bioactive compounds, and some health-promoting features of guava juice was investigated. Results showed a significant (p < .05) decrease in pH, total soluble solids, glucose and fructose residues, vitamin C, and total carotenoids after 32 h of fermentation. Total phenolic content, free radical scavenging abilities, and ferrous reducing power were markedly enhanced during the fermentation process. Moreover, fermented juice represented good enzyme inhibition abilities (α-amylase and α-glucosidase) and anti-inflammatory activities. The initial amount of angiotensin-converting enzyme inhibitory activity (26.5%) increased to 72.1% and 66.4% in L. plantarum subsp. plantarum 1896 and L. plantarum subsp. plantarum 1745 treatments, respectively. These findings reveal that guava juice fermentation with the studied Lactobacillus strains can be a promising strategy to augment the functional properties of the fruit-based beverage.

Antidiabetic Activity of the Methanol Fraction of Sungkai Leaves (Peronema canescens Jack)

Diabetes Mellitus (DM) is one of a group of metabolic diseases characterized by hyperglycemia caused by a disturbance in insulin so that blood glucose levels increase. Prevention of absorption of blood glucose by the intestine can be done with the help of the enzyme α-glucosidase. Based on the results of phytochemical tests, it is known that the methanol fraction of sungkai leaves contains flavonoid compounds. The Fourier Transform Infra-Red (FTIR) spectrum showed that the isolates had phenolic O-H groups (3,354.53 cm1 , 1,359.28 cm-1 ), aromatic C=C group (1,615.48 cm-1 ), C-O-C ether group (1,046.60 cm-1 ) and aromatic C-H group (822.21 cm-1 ). In vivo antidiabetic activity test was carried out using test animals of white male mice which were induced by alloxan. Antidiabetic testing was carried out using 6 treatment groups with glibenclamide, Na-Carboxymethyl cellulose (NaCMC) 0.5%, dose 175 mg/kgBW, 350 mg/kgBW, 700 mg/kg Body Weight (BW) and isolates 2 mg/kgBW. The results showed that the methanol fraction of sungkai leaves had the best antidiabetic activity at a dose of isolate and 700 mg/kgBW which was able to reduce blood glucose levels by 42.20% and 42.00%. In vitro antidiabetic testing through αglucosidase enzyme inhibition mechanism did not show any antidiabetic activity at concentrations of fractions 5, 10, 25, 50 and 100 ppm.