Deciphering the Potential Therapeutic Effects of Hydnocarpus wightianus Seed Extracts using in vitro and in silico approaches.

Phytocompounds possess the potential to treat a broad spectrum of disorders due to their remarkable bioactivity. Naturally occurring compounds possess lower toxicity profiles, which making them attractive targets for drug development. Hydnocarpus wightianus seeds were extracted using ethanol, acetone, and hexane solvents. The extracts were evaluated for phytochemicals screening and other therapeutic characteristics, such as free radicals scavenging, anti α-amylase, anti α-glucosidase, and anti-bacterial activities. The ethanolic extract exhibited noteworthy antibacterial characteristics and demonstrated considerable antioxidant, and anti-diabetic effects. The IC50 value of the ethanolic extract for Dpph, α-amylase, and α-glucosidase were found to be 77.299 ± 3.381 µg/mL, 165.56 2.56 µg/mL, and 136.58 ± 5.82 µg/mL, respectively. The ethanolic extract was effective against Methicillin resistant Staphylococcus aureus (26 mm zone of inhibition at 100 µL concentration). Molecular docking investigations revealed the phytoconstituent's inhibitory mechanisms against diabetic, free radicals, and bacterial activity. Docking score for phytocompounds against targeted protein varies from -7.2 to -5.1 kcal/mol. The bioactive compounds present in the ethanolic extract were identified by Gas chromatography/Mass spectrometry analysis, followed by molecular docking and molecular dynamic simulation studies to further explore the phytoconstituent's inhibitory mechanism of α-glucosidase, ∝-amylase, radical scavenging, and bacterial activity. The electronic structure and possible pharmacological actions of the phytocompound were revealed through the use of Density Functional Theory (DFT) analysis. Computational and in vitro studies revealed that these identified compounds have anti-diabetic, anti-oxidant, and anti-bacterial activities against antibiotic-resistant strain of Staphylococcus aureus.

Dynamics of small molecule-enzyme interactions: Novel benzenesulfonamides as multi-target agents endowed with inhibitory effects against some metabolic enzymes.

In contemporary medicinal chemistry, employing a singular small molecule to concurrently multi-target disparate molecular entities is emerging as a potent strategy in the ongoing battle against metabolic disease. In this study, we present the meticulous design, synthesis, and comprehensive biological evaluation of a novel series of 1,2,3-triazolylmethylthio-1,3,4-oxadiazolylbenzenesulfonamide derivatives (8a-m) as potential multi-target inhibitors against human carbonic anhydrase (EC.4.2.1.1, hCA I/II), α-glycosidase (EC.3.2.1.20, α-GLY), and α-amylase (EC.3.2.1.1, α-AMY). Each synthesized sulfonamide underwent rigorous assessment for inhibitory effects against four distinct enzymes, revealing varying degrees of hCA I/II, a-GLY, and a-AMY inhibition across the tested compounds. hCA I was notably susceptible to inhibition by all compounds, demonstrating remarkably low inhibition constants (KI) ranging from 42.20 ± 3.90 nM to 217.90 ± 11.81 nM compared to the reference standard AAZ (KI of 439.17 ± 9.30 nM). The evaluation against hCA II showed that most of the synthesized compounds exhibited potent inhibition effects with KI values spanning the nanomolar range 16.44 ± 1.53-70.82 ± 4.51 nM, while three specific compounds, namely 8a-b and 8d, showcased lower inhibitory potency than other derivatives that did not exceed that of the reference drug AAZ (with a KI of 98.28 ± 1.69 nM). Moreover, across the spectrum of synthesized compounds, potent inhibition profiles were observed against diabetes mellitus-associated α-GLY (KI values spanning from 0.54 ± 0.06 µM to 5.48 ± 0.50 µM), while significant inhibition effects were noted against α-AMY, with IC50 values ranging between 0.16 ± 0.04 µM and 7.81 ± 0.51 µM) compared to reference standard ACR (KI of 23.53 ± 2.72 µM and IC50 of 48.17 ± 2.34 µM, respectively). Subsequently, these inhibitors were evaluated for their DPPH· and ABTS+· radical scavenging activity. Moreover, molecular docking investigations were meticulously conducted within the active sites of hCA I/II, α-GLY, and α-AMY to provide comprehensive elucidation and rationale for the observed inhibitory outcomes.

Synthesis of obovatol and related neolignan analogues as α-glucosidase and α-amylase inhibitors.

Diabetes mellitus is a metabolic disease characterized by hyperglycemia, which can be counteracted by the inhibition of α-glucosidase (α-Glu) and α-amylase (α-Amy), enzymes responsible for the hydrolysis of carbohydrates. In recent decades, many natural compounds and their bioinspired analogues have been studied as α-Glu and α-Amy inhibitors. However, no studies have been devoted to the evaluation of α-Glu and α-Amy inhibition by the neolignan obovatol (1). In this work, we report the synthesis of 1 and a library of new analogues. The synthesis of these compounds was achieved by implementing methodologies based on: phenol allylation, Claisen/Cope rearrangements, methylation, Ullmann coupling, demethylation, phenol oxidation and Michael-type addition. Obovatol (1) and ten analogues were evaluated for their in vitro inhibitory activity towards α-Glu and α-Amy. Our investigation highlighted that the naturally occurring 1 and four neolignan analogues (11, 22, 26 and 27) were more effective inhibitors than the hypoglycemic drug acarbose (α-Amy: 34.6 µM; α-Glu: 248.3 µM) with IC5O value of 6.2-23.6 µM toward α-Amy and 39.8-124.6 µM toward α-Glu. Docking investigations validated the inhibition outcomes, highlighting optimal compatibility between synthesized neolignans and both the enzymes. Concurrently circular dichroism spectroscopy detected the conformational changes in α-Glu induced by its interaction with the studied neolignans. Detailed studies through fluorescence measurements and kinetics of α-Glu and α-Amy inhibition also indicated that 1, 11, 22, 26 and 27 have the greatest affinity for α-Glu and 1, 11 and 27 for α-Amy. Surface plasmon resonance imaging (SPRI) measurements confirmed that among the compounds studied, the neolignan 27 has the greater affinity for both enzymes, thus corroborating the results obtained by kinetics and fluorescence quenching. Finally, in vitro cytotoxicity of the investigated compounds was tested on human colon cancer cell line (HCT-116). All these results demonstrate that these obovatol-based neolignan analogues constitute promising candidates in the pursuit of developing novel hypoglycemic drugs.

Unveiling anti-diabetic potential of new thiazole-sulfonamide derivatives: Design, synthesis, in vitro bio-evaluation targeting DPP-4, α-glucosidase, and α-amylase with in-silico ADMET and docking simulation.

Diabetes mellitus type 2 (T2DM) can be managed by targeting dipeptidyl peptidase-4 (DPP-4), an enzyme that breaks down and deactivates peptides such as GIP and GLP-1. In this context, a new series of 2-(2-substituted hydrazineyl)thiazole derivatives 4, 5, 6, 8, 10, and 11 conjugated with the 2-hydroxy-5-(pyrrolidin-1-ylsulfonyl)benzylidene fragment were designed and synthesized. The virtual screening of the designed derivatives inside DPP-4 demonstrated good to moderate activity, with binding affinity ranging from -6.86 to -5.36 kcal/mol compared to Sitagliptin (S=-5.58 kcal/mol). These results encourage us to evaluate DPP-4 using in-vitro fluorescence-based assay. The in-vitro results exhibited inhibitory percentage (IP) values ranging from 40.66 to 75.62 % in comparison to Sitagliptin (IP=63.14 %) at 100 µM. Subsequently, the IC50 values were determined, and the 5-aryl thiazole derivatives 10 and 11 revealed strong potent IC50 values 2.75 ± 0.27 and 2.51 ± 0.27 µM, respectively, compared to Sitagliptin (3.32 ± 0.22 µM). The SAR study exhibited the importance of the substituents on the thiazole scaffold, especially with the hydrophobic fragment at C5 of the thiazole, which has a role in the activity. Compounds 10 and 11 were further assessed toward α-glucosidase and α-amylase enzymes and give promising results. Compound 10 showed good activity against α-glucosidase with IC50 value of 3.02 ± 0.23 µM compared to Acarbose 3.05 ± 0.22 µM and (11 = 3.34 ± 0.10 µM). On the other hand, for α-amylase, compound 11 was found to be most effective with IC50 value of 2.91 ± 0.23 µM compared to compound 10 = 3.30 ± 0.16 µM and Acarbose (2.99 ± 0.21 µM) indicating that these derivatives could reduce glucose by more than one target. The most active derivatives 10 and 11 attracted great interest as candidates for oral bioavailability and safe toxicity profiles compared to positive controls. The in-silico docking simulation was performed to understand the binding interactions inside the DPP-4, α-glucosidase, and α-amylase pockets, and it was found to be promising antidiabetic agents through a number of interactions.

Novel acyl hydrazide derivatives of polyhydroquinoline as potent anti-diabetic and anti-glycating agents: Synthesis, in vitro α-amylase, α-glucosidase inhibition and anti-glycating activity with molecular docking insights.

In this study, eleven novel acyl hydrazides derivative of polyhydroquinoline were synthesized, characterized and screened for their in vitro anti-diabetic and anti-glycating activities. Seven compounds 2a, 2d, 2i, 2 h, 2j, 2f, and 2 g exhibited notable α-amylase inhibitory activity having IC50 values from 3.51 ± 2.13 to 11.92 ± 2.30 µM. Similarly, six compounds 2d, 2f, 2 h, 2i, 2j, and 2 g displayed potent α-glucosidase inhibitory activity compared to the standard acarbose. Moreover, eight derivatives 2d, 2 g, 2f, 2j, 2a, 2i, 2 g, and 2e showed excellent anti-glycating activity with IC50 values from 6.91 ± 2.66 to 15.80 ± 1.87 µM when compared them with the standard rutin (IC50 = 22.5 ± 0.90 µM). Molecular docking was carried out to predict the binding modes of all the compounds with α-amylase and α-glucosidase. The docking analysis revealed that most of the compounds established strong interactions with α-amylase and α-glucosidase. All compounds fitted well into the binding pockets of α-amylase and α-glucosidase. Among all compounds 2a and 2f were most potent based on docking score -8.2515 and -7.3949 against α-amylase and α-glucosidase respectively. These results hold promise for the development of novel candidates targeted at controlling postprandial glucose levels in individuals with diabetes.

Discovery of novel thiazole derivatives containing pyrazole scaffold as PPAR-γ Agonists, α-Glucosidase, α-Amylase and COX-2 inhibitors; Design, synthesis and in silico study.

A novel series of thiazole derivatives with pyrazole scaffold 16a-l as hybrid rosiglitazone/celecoxib analogs was designed, synthesized and tested for its PPAR-γ activation, α-glucosidase, α-amylase and COX-2 inhibitory activities. Regarding the anti-diabetic activity, all compounds were assessed in vitro against PPAR-γ activation, α-glucosidase and α-amylase inhibition in addition to in vivo hypoglycemic activity (one day and 15 days studies). Compounds 16b, 16c, 16e and 16 k showed good PPAR-γ activation (activation % ≈ 72-79 %) compared to that of the reference drug rosiglitazone (74 %). In addition, the same derivatives 16b, 16c, 16e and 16 k showed the highest inhibitory activities against α-glucosidase (IC50 = 0.158, 0.314, 0.305, 0.128 µM, respectively) and against α-amylase (IC50 = 32.46, 23.21, 7.74, 35.85 µM, respectively) compared to the reference drug acarbose (IC50 = 0.161 and 31.46 µM for α-glucosidase and α-amylase, respectively). The most active derivatives 16b, 16c, 16e and 16 k also revealed good in vivo hypoglycemic effect comparable to that of rosiglitazone. In addition, compounds 16b and 16c had the best COX-2 selectivity index (S.I. = 18.7, 31.7, respectively) compared to celecoxib (S.I. = 10.3). In vivo anti-inflammatory activity of the target derivatives 16b, 16c, 16e and 16 k supported the results of in vitro screening as the derivatives 16b and 16c (ED50 = 8.2 and 24 mg/kg, respectively) were more potent than celecoxib (ED50 = 30 mg/kg). In silico docking, ADME, toxicity, and molecular dynamic studies were carried out to explain the interactions of the most active anti-diabetic and anti-inflammatory compounds 16b, 16c, 16e and 16 k with the target enzymes in addition to their physiochemical parameters.

Pyrano[2,3-c]pyrazole fused spirooxindole-linked 1,2,3-triazoles as antioxidant agents: Exploring their utility in the development of antidiabetic drugs via inhibition of α-amylase and DPP4 activity.

Environment-benign, multicomponent synthetic methodologies are vital in modern pharmaceutical research and facilitates multi-targeted drug development via synergistic approach. Herein, we reported green and efficient synthesis of pyrano[2,3-c]pyrazole fused spirooxindole linked 1,2,3-triazoles using a tea waste supported copper catalyst (TWCu). The synthetic approach involves a one-pot, five-component reaction using N-propargylated isatin, hydrazine hydrate, ethyl acetoacetate, malononitrile/ethyl cyanoacetate and aryl azides as model substrates. Mechanistically, the reaction was found to proceed via in situ pyrazolone formation followed by Knoevenagel condensation, azide alkyne cycloaddition and Michael's addition reactions. The molecules were developed using structure-based drug design. The primary goal is to identifying anti-oxidant molecules with potential ability to modulate α-amylase and DPP4 (dipeptidyl-peptidase 4) activity. The anti-oxidant analysis, as determined via DPPH, suggested that the synthesized compounds, A6 and A10 possessed excellent anti-oxidant potential compared to butylated hydroxytoluene (BHT). In contrast, compounds A3, A5, A8, A9, A13, A15, and A18 were found to possess comparable anti-oxidant potential. Among these, A3 and A13 possessed potential α-amylase inhibitory activity compared to the acarbose, and A3 further emerged as dual inhibitors of both DPP4 and α-amylase with anti-oxidant potential. The relationship of functionalities on their anti-oxidant and enzymatic inhibition was explored in context to their SAR that was further corroborated using in silico techniques and enzyme kinetics.

Evaluation of the Antimicrobial Activity of Triple Enzyme-Embedded Organic-Inorganic Hybrid Nanoflowers (hNFs) in Comparison with Powerful Antimicrobial Agent Chitosan.

Organic-inorganic hybrid nanoflowers (hNFs) have high stability, reusability, low production cost, and overcome substrate/product inhibition. Antimicrobial activity of various hNFs has been reported to overcome environmental microbial contaminations and infections, which are considered major public health problems. α-amylase, protease, and lipase are the most common industrial enzymes exerting antimicrobial activity; therefore, we synthesized triple enzyme (α-amylase, protease, and lipase)-embedded hNFs by using pancreatin to evaluate their antimicrobial activity in comparison with one of the most potent antimicrobial polymer chitosan. The broad spectrum of the antimicrobial properties of chitosan is used in industrial products, including cosmetics, food, agriculture, pharmaceuticals, and textiles. SEM analysis, thermogravimetric analysis (TGA), and the degree of deacetylation (%DD) were performed for chitosan characterization, where SEM, FTIR, EDX, and XRD analyses were performed for the characterization of hNFs. The catalytic activity of pancreatin and hNFs was evaluated by measuring lipase, α-amylase, and protease enzyme activities at 37 °C. Antibacterial activities of hNFs, pancreatin, and chitosan were tested on gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) bacteria, compared to the pancreatin and chitosan via agar and broth dilution methods. hNFs showed enhanced catalytic activity for protease, lipase, and α-amylase compared to pancreatin at different pH values (pH 8, 9). hNFs showed catalytic activity after being washed and reused up to six times, indicating their reusability and recoverability. hNFs showed significant antimicrobial activity, such as chitosan, Staphylococcus aureus, and Escherichia coli, compared to pancreatin. Our novel hNFs can be used to develop antimicrobial technologies to fight against environmental microbial contaminations and antibiotic resistance-driven environmental pathogens.

New natural protein tyrosine phosphatase 1B inhibitors from Gynostemma pentaphyllum.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease mainly caused by insulin resistance, which can lead to a series of complications such as cardiovascular disease, retinopathy, and its typical clinical symptom is hyperglycaemia. Glucosidase inhibitors, including Acarbose, Miglitol, are commonly used in the clinical treatment of hypoglycaemia. In addition, Protein tyrosine phosphatase 1B (PTP1B) is also an important promising target for the treatment of T2DM. Gynostemma pentaphyllum is a well-known oriental traditional medicinal herbal plant, and has many beneficial effects on glucose and lipid metabolism. In the present study, three new and nine known dammarane triterpenoids isolated from G. pentaphyllum, and their structures were elucidated by spectroscopic methods including HR-ESI-MS,1H and 13C NMR and X-ray crystallography. All these compounds were evaluated for inhibitory activity against α-glucosidase, α-amylase and PTP1B. The results suggested that compounds 7∼10 were potential antidiabetic agents with significantly inhibition activity against PTP1B in a dose-dependent manner.

Fluorinated indeno-quinoxaline bearing thiazole moieties as hypoglycaemic agents targeting α-amylase, and α-glucosidase: synthesis, molecular docking, and ADMET studies.

Inhibition of α-glucosidase and α-amylase are key tactics for managing blood glucose levels. Currently, stronger, and more accessible inhibitors are needed to treat diabetes. Indeno[1,2-b] quinoxalines-carrying thiazole hybrids 1-17 were created and described using NMR. All analogues were tested for hypoglycaemic effect against STZ-induced diabetes in mice. Compounds 4, 6, 8, and 16 were the most potent among the synthesised analogues. These hybrids were examined for their effects on plasma insulin, urea, creatinine, GSH, MDA, ALT, AST, and total cholesterol. Moreover, these compounds were tested against α-glucosidase and α-amylase enzymes in vitro. The four hybrids 4, 6, 8, and 16 represented moderate to potent activity with IC50 values 0.982 ± 0.04, to 10.19 ± 0.21 for α-glucosidase inhibition and 17.58 ± 0.74 to 121.6 ± 5.14 µM for α-amylase inhibition when compared to the standard medication acarbose with IC50=0.316 ± 0.02 µM for α-glucosidase inhibition and 31.56 ± 1.33 µM for α-amylase inhibition. Docking studies as well as in silico ADMT were done.

Investigation into the Phytochemical Composition, Antioxidant Properties, and In-Vitro Anti-Diabetic Efficacy of Ulva lactuca Extracts.

In this research, the chemical compositions of various extracts obtained from Ulva lactuca, a type of green seaweed collected from the Nador lagoon in the northern region of Morocco, were compared. Their antioxidant and anti-diabetic properties were also studied. Using GC-MS technology, the fatty acid content of the samples was analyzed, revealing that palmitic acid, eicosenoic acid, and linoleic acid were the most abundant unsaturated fatty acids present in all samples. The HPLC analysis indicated that sinapic acid, naringin, rutin, quercetin, cinnamic acid, salicylic acid, apigenin, flavone, and flavanone were the most prevalent phenolic compounds. The aqueous extract obtained by maceration showed high levels of polyphenols and flavonoids, with values of 379.67 ± 0.09 mg GAE/g and 212.11 ± 0.11 mg QE/g, respectively. This extract also exhibited an impressive ability to scavenge DPPH radicals, as indicated by its IC50 value of 0.095 ± 0.12 mg/mL. Additionally, the methanolic extract obtained using the Soxhlet method demonstrated antioxidant properties by preventing ß-carotene discoloration, with an IC50 of 0.087 ± 0.14 mg/mL. Results from in-vitro studies showed that extracts from U. lactuca were able to significantly inhibit the enzymatic activity of α-amylase and α-glucosidase. Among the various extracts, methanolic extract (S) has been identified as the most potent inhibitor, exhibiting a statistically similar effect to that of acarbose. Furthermore, molecular docking models were used to evaluate the interaction between the primary phytochemicals found in these extracts and the human pancreatic α-amylase and α-glucosidase enzymes. These findings suggest that U. lactuca extracts contain bioactive substances that are capable of reducing enzyme activity more effectively than the commercially available drug, acarbose.

Spectrum-effect relationship between HPLC fingerprint and hypoglycemic of litchi leaves (Litchi chinensis Sonn) in vitro.

Litchi chinensis Sonn (Litchi) has been listed in the Chinese Pharmacopeia, and is an economically and medicinally valuable species within the family Sapindaceae. However, the material basis of its pharmacological action and the pharmacodynamic substances associated with its hypoglycemic effect are still unclear. The predominant objective of this study was to establish the fingerprint profile of litchi leaves and to evaluate the relationship between the components of the high-performance liquid chromatography (HPLC) fingerprint of litchi leaves, assess its hypoglycemic effect by measuring α-glucosidase and α-amylase inhibition, and find the spectrum-effect relationship of litchi leaves by bivariate correlation analysis, Grey relational analysis and partial least squares regression analysis. In this study, the fingerprint of litchi leaves was established by HPLC, and a total of 15 common peaks were identified that clearly calibrated eight components, with P1 being gallic acid, P2 being protocatechuic acid, P3 being catechin, P6 being epicatechin, P12 being rutin, P13 being astragalin, P14 being quercetin and P15 being kaempferol. The similarities between the fingerprints of 11 batches of litchi leaves were 0.766-0.979. Simultaneously, the results of the spectrum-effect relationship showed that the chemical constituents represented by peaks P8, P3, P12, P14, P2, P13, and P11 were relevant to the hypoglycemic effect.

ß(1,3) ß(1,6) glucogalactan from Rhizopus microsporus var. oligosporus: extraction, characterization, antioxidant and α-amylase inhibitory activities.

In this study, the Box-Behnken experimental planning was used to optimize the extraction of polysaccharides from the cell wall of Rhizopus microspore var. oligosporus, with analysis of the quantitative effects of parameters pH, temperature and extraction time for polysaccharide yield. The optimal conditions for extraction were determined by the regression equation and evaluation of the response surface graphs, which indicated: pH 13, temperature of 120ºC and time of 60 min, with maximum yield around 18.5%. Fourier transform infrared spectroscopy analysis indicated typical polysaccharide signals. Nuclear magnetic resonance spectroscopy and monosaccharide analysis indicated a ß(1,3) ß(1,6) glucogalactan. The polysaccharide exhibited an average molecular weight of 120 kDa and a polymerization degree of 741. Antioxidant assays in vitro revealed the potential of polysaccharide in elimination of ABTS+ radical and hydroxyl radicals. EC50 values for free radical elimination were 7.69 and 17.8 mg/mL, for ABTS+ and hydroxyls, respectively. The polysaccharides showed potential for α-amylase inhibition with an EC50 of 1.66 mg/mL. The results suggest that ß(1,3) ß(1,6) glucogalactan from Rhizopus microsporus var. oligosporus can be used in biotechnological applications.

Four Undescribed Stilbenoid Derivatives from the Aerial Parts of Dendrobium officinale with their α-Glucosidase and α-Amylase Inhibitory Activity.

In this study, four undescribed bibenzyl derivatives (1-4), together with seven known compounds (5-11) were isolated from the aerial parts of Dendrobium officinale. Their chemical structures were determined to be (7'S,8'S) -9''-acetyldendrocandin U (1), (7'S,8'S) -4'-methoxydendrocandin T (2), (7'R,8'S) -dendrocandin B (3), (1S,2R) -5'''-methoxydendrofindlaphenol C (4) by analyzing of the spectroscopic data including HR-ESI-MS, 1D-, and 2D-NMR spectra. The absolute configurations of compounds 1-4 were determined by the electronic circular dichroism (ECD) spectra. Compounds 1-3, 5, 10 and 11 inhibited α-glucosidase with the IC50 values ranging from 56.3 to 165.3 µM, compounds 1-3, 5, 7-10 inhibited α-amylase with the IC50 values ranging from 65.2 to 177.6 µM.

Phenolic Profile, Bioactivities and In Silico Analysis of the Trunk Bark of Acacia Cyanophylla Lindl.

In the current investigation, total phenolics and flavonoids of the methanolic extract obtained from the trunk bark of Acacia cyanophylla Lindl. were quantified by LC-HRMS technique. DPPH and ABTS reagents were employed to assay the antioxidant potential. The anti-tyrosinase and anti-α-amylase potentials were also assayed. The findings revealed that thirteen polyphenolic compounds were detected in the methanolic extract with trans-taxifolin (23.2 g/kg), as the major constituent. A. cyanophylla extract displayed a higher activity with DPPH test (IC50=10.14±1.00 µg/mL) than with ABTS (IC50=15.27±2.09 µg/mL). The same extract also exhibited interesting α-amylase inhibitory action (IC50 value of 4.00±0.17 µg/mL). Moreover, methanolic trunk bark extract exerted strong anti-tyrosinase capacity with an IC50 of 5.12±0.41 µg/mL in comparison to kojic acid (IC50=10.22±0.85 µg/mL) used as positive control. The antioxidant, anti-tyrosinase and anti-α-amylase potentials of the methanolic extract of A. cyanophylla trunk bark were reinforced by in silico molecular docking analyses, which confirmed the results of the in vitro tests.

Phytochemical Profile, Antioxidant, Enzyme Inhibition, Acute Toxicity, In Silico Molecular Docking and Dynamic Analysis of Apis Mellifera Propolis as Antidiabetic Supplement.

This study aims to identify the phytochemical profile of Apis mellifera propolis and explore the potential of its anti-diabetic activity through inhibition of α-amylase (α-AE), α-glucosidase(α-GE), as well as novel antidiabetic compounds of propolis. Apis mellifera propolis extract (AMPE) exhibited elevated polyphenol 33.26±0.17 (mg GAE/g) and flavonoid (15.45±0.13 mg RE/g). It also indicated moderate strong antioxidant activity (IC50 793.09±1.94 µg/ml). This study found that AMPE displayed promising α-AE and α-GE inhibition through in vitro study. Based on LC-MS/MS screening, 18 unique AMPE compounds were identified, with majorly belonging to anthraquinone and flavonoid compounds. Furthermore, in silico study determined that 8 compounds of AMPE exhibited strong binding to α-AE that specifically interacted with its catalytic residue of ASP197. Moreover, 2 compounds exhibit potential inhibition of α-GE, by interacting with crucial amino acids of ARG315, ASP352, and ASP69. Finally, we suggested that 2,7-Dihydroxy-1-(p-hydroxybenzyl)-4-methoxy-9,10-dihydrophenanthrene and 3(3-(3,4-Dihydroxybenzyl)-7-hydroxychroman-4-one as novel inhibitors of α-AE and α-GE. Notably, these compounds were initially discovered from Apis mellifera propolis in this study. The molecular dynamic analysis confirmed their stable binding with both enzymes over 100 ns simulations. The in vivo acute toxicity assay reveals AMPE as a practically non-toxic product with an LD50 value of 16,050 mg/kg. Therefore, this propolis may serve as a promising natural product for diabetes mellitus treatment.

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 ß-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.

Combining the Pharmaceutical and Toxicological Properties of Selected Essential Oils with their Chemical Components by GC-MS Analysis.

In the current investigation, a comprehensive analysis was carried out on essential oils (EOs) extracted from six aromatic plant species, namely Rosmarinus officinalis, Pelargonium graveolens, Thymus vulgaris, Origanum vulgare, Laurus nobilis, and Aloysia citrodora. An exploration was conducted into the chemical composition using Gas Chromatography-Mass Spectrometry (GC/MS), antioxidant properties assessed through DPPH, ABTS, CUPRAC, FRAP, MCA, and PBD assays, ecotoxicological impacts evaluated via allelopathy and the Daphnia magna heartbeat test, as well as bio-pharmacological effects including anticancer activity and gene expression analysis. Results revealed strong antioxidant activity in all essential oils, with T. vulgaris EO (2748.00 mg TE/g) and O. vulgare EO (2609.29 mg TE/g) leading in CUPRAC assay. R. officinalis EO showed the highest α-amylase inhibition at 1.58 mmol ACAE/g, while O. vulgare EO excelled in α-glucosidase inhibition at 1.57 mmol ACAE/g. Additionally, cytotoxic effects were evaluated on human colorectal cancer (HCT116) cells. A. citrodora, O. vulgare, and R. officinalis EOs were found the most potent anticancer, as also witnessed by their higher modulatory effects on the gene expression of BAX and Bcl-2. Collectively, the present data highlight the importance to implement the knowledge and to valorize the supply chain of aromatic plants.

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.

Evaluation of Phytochemistry and Antidiabetic Potential of an Astragalus Species (Astragalus kurdicus Boiss.).

Astragalus kurdicus Boiss. roots are used in folk medicine for antidiabetic purposes. Different Astragalus plant metabolites have a notable potential for antidiabetic activity through varying mechanisms. Herein, this study is designed to assess the antidiabetic activity of Astragalus kurdicus total (AKM: methanol extract, yield: 14.53 %) and sub-extracts (AKB: n-butanol, AKC: chloroform, AKW: water, AKH: hexane extracts), utilizing a range of diabetes-related in vitro methodologies, and to investigate the chemical composition of the plant. The highest astragaloside and saponin content was seen in AKB extract. Among the measured saponins, the abundance of Astragaloside IV (27.41 µg/mg in AKM) was the highest in high-performance thin-layer chromatography (HPTLC) analysis. Furthermore, flavonoid-rich AKC was found to be mostly responsible for the high antioxidant activity. According to the results of the activity tests, AKW was the most active extract in protein tyrosine phosphatase 1 B (PTP1B), dipeptidyl peptidase IV (DPP4), and α-amylase inhibition tests (percent inhibitions are: 87.17 %, 82.4 %, and 91.49 % respectively, at 1 mg/mL). AKM and AKW demonstrated the highest efficacy in stimulating the growth of prebiotic microorganisms and preventing the formation of advanced glycation end products (AGEs). Thus, for the first time, the antidiabetic activity of A. kurdicus was evaluated from various perspectives.