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1.
BMC Complement Med Ther ; 24(1): 73, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308284

RESUMO

Citrus fruit essential oil is considered one of the widely studied essential oils while its leaves attract less attention although being rich in nearly the same composition as the peel and flowers. The leaves of bitter orange or sour orange (Citrus aurantium L.) were extracted using three different techniques namely; hydrodistillation (HD), steam distillation (SD), and microwave-assisted distillation (MV) to compare their chemical composition. The three essential oil samples were analyzed through GC/FID and GC/MS analyses. The samples were tested in vitro using different antioxidant techniques (DPPH, ABTS, CUPRAC, FRAP, PBD, and MCA), neuroprotective enzyme inhibitory activities (acetylcholine and butyl choline enzymes), and antidiabetic activities (α-amylase and α-glucosidase). The results showed that thirty-five volatile ingredients were detected and quantified. Monoterpenes represented the most abundant class in the three essential oils followed by sesquiterpenes. C. aurantium essential oil carried potential antioxidant activity where SD exhibited the highest antioxidant activity, with values arranged in the following order: FRAP (200.43 mg TE/g), CUPRAC (138.69 mg TE/g), ABTS (129.49 mg TE/g), and DPPH (51.67 mg TE/g). SD essential oil also presented the most potent α-amylase (0.32) inhibition while the MV essential oil showed the highest α-glucosidase inhibition (2.73 mmol ACAE/g), followed by HD (2.53 mmol ACAE/g), and SD (2.46 mmol ACAE/g). The SD essential oil exhibited the highest BChE and AChE inhibitory activities (3.73 and 2.06 mg GALAE/g), respectively). Thus, bitter orange essential oil can act as a potential source of potent antioxidant, antidiabetic, and neuroprotective activities for future drug leads.


Assuntos
Doença de Alzheimer , Benzotiazóis , Citrus , Fármacos Neuroprotetores , Óleos Voláteis , Ácidos Sulfônicos , Antioxidantes/química , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Citrus/química , Destilação , Doença de Alzheimer/tratamento farmacológico , alfa-Glucosidases , Extratos Vegetais/farmacologia , Extratos Vegetais/química , alfa-Amilases
2.
Food Funct ; 15(4): 2234-2248, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38318730

RESUMO

A promising and efficacious approach to manage diabetes is inhibiting α-glucosidase and α-amylase activity. Therefore, the inhibitory activities of five natural sweeteners (mogrosides (Mog), stevioside (Ste), glycyrrhizinic acid (GA), crude trilobatin (CT), and crude rubusoside (CR)) against α-glucosidase and α-amylase and their interactions were evaluated in vitro using enzyme kinetics, fluorescence spectroscopy, Fourier infrared spectroscopy, and molecular docking. The inhibitor sequence was CT > GA > Ste, as GA competitively inhibited α-glycosidase activity while CT and Ste exhibited mixed inhibitory effects. Compared to a positive control acarbose, the inhibitory activity of CT was higher. For α-amylase, the mixed inhibitors CT, CR, and Mog and the competitive inhibitor Ste effectively inhibited the enzyme, with the following order: CT > CR > Ste > Mog; nevertheless, the inhibitors were slightly inferior to acarbose. Three-dimensional fluorescence spectra depicted that GA, CT, and CR bound to the hydrophobic cavity of α-glucosidase or α-amylase and changed the polarity of the hydrophobic amino acid-based microenvironment and structure of the polypeptide chain backbone. Infrared spectroscopy revealed that GA, CT, and CR could disrupt the secondary structure of α-glucosidase or α-amylase, which decreased enzyme activity. GA, trilobatin and rubusoside bound to amino acid residues through hydrogen bonds and hydrophobic interactions, changing the conformation of enzyme molecules to decrease the enzymatic activity. Thus, CT, CR and GA exhibit promising inhibitory effects against α-glucosidase and α-amylase.


Assuntos
Acarbose , Diterpenos do Tipo Caurano , Flavonoides , Glucosídeos , Inibidores de Glicosídeo Hidrolases , Polifenóis , Acarbose/farmacologia , Acarbose/química , Inibidores de Glicosídeo Hidrolases/química , Simulação de Acoplamento Molecular , alfa-Glucosidases/metabolismo , alfa-Amilases/metabolismo , Estrutura Secundária de Proteína , Aminoácidos
3.
Sci Rep ; 14(1): 1161, 2024 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-38216714

RESUMO

During adolescence, students increasingly report suffering from stress and school burnout, which poses a risk to students' healthy development. However, social support may counteract perceived stress according to the Buffering Hypothesis and the Conservation of Resources Theory. In search of factors that would support healthy student development, studies have primarily focused on self-report data and neglected biophysiological processes. Addressing this research desideratum, this study examined whether perceived social support buffers the interplay of self-reported stress considering biophysiological markers (i.e., cortisol, alpha-amylase, oxidative stress, and telomere length). 83 secondary school students (Mage = 13.72, SD = 0.67; 48% girls) from Germany participated in a questionnaire study and biophysiological testing. Moderation analyses in R revealed that support from parents moderated the relationships between psychological stress as well as cynicism and inadequacy at school linked to alpha-amylase.


Assuntos
Grupo Associado , Instituições Acadêmicas , Feminino , Adolescente , Humanos , Masculino , Estudantes/psicologia , Pais/psicologia , alfa-Amilases
4.
Sci Total Environ ; 915: 170036, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38242479

RESUMO

Plastic fragments are widely distributed in different environmental media and has recently drawn special attention due to its difficulty in degradation and serious health and environmental problems. Among, nanoplastics (NPs) are smaller in size, larger in surface/volume ratio, and more likely to easily adsorb ambient pollutants than macro plastic particles. Moreover, NPs can be easily absorbed by wide variety of organisms and accumulate in multiple tissues/organs and cells, thus posing a more serious threat to living organisms. Alpha-amylase (α-amylase) is a hydrolase, which can be derived from various sources such as animals, plants, and microorganisms. Currently, no studies have concentrated on the binding of NPs with α-amylase and their interaction mechanisms by employing a multidimensional strategy. Hence, we explored the interaction mechanisms of polystyrene nanoplastics (PS-NPs) with α-amylase by means of multispectral analysis, in vitro enzymatic activity analysis, and molecular simulation techniques under in vitro conditions. The findings showed that PS-NPs had the capability to bind with the intrinsic fluorescence chromophores, leading to fluorescence changes of these specific amino acids. This interaction also caused the alterations in the micro-environment of the fluorophore residues mainly tryptophan (TRP) and tyrosine (TYR) residues of α-amylase. PS-NPs interaction promoted the unfolding and partial expansion of polypeptide chains and the loosening of protein skeletons, and destroyed the secondary structure (increased random coil contents and decreased α-helical contents) of this protein, forming a larger particle size of the PS-NPs-α-amylase complex. Moreover, the enzymatic activity of α-amylase in vitro was found to be inhibited in a concentration dependent manner, thereby impairing its physiological functions. Further molecular simulation found that PS-NPs had a higher tendency to bind to the active site of α-amylase, which is the cause for its structural and functional changes. Additionally, the hydrophobic force played a major role in mediating the binding interactions between PS-NPs and α-amylase. Taken together, our study indicated that PS-NPs interaction can initiate the abnormal physiological functions of α-amylase through PS-NPs-induced structural and conformational alternations.


Assuntos
Nanopartículas , Poluentes Químicos da Água , Animais , Poliestirenos/metabolismo , Microplásticos , alfa-Amilases , Nanopartículas/química , Poluentes Químicos da Água/metabolismo
5.
J Agric Food Chem ; 72(5): 2667-2677, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38287914

RESUMO

Nectarine [Prunus persica (L.) Batsch var.] fruits are highly susceptible to cracking during the ripening process, which significantly decreases their commercial value. In this study, we investigated the underlying mechanism of nectarine fruit-cracking using two nectarine varieties, namely, "Qiannianhong" (cracking-susceptible) and "CR1012" (cracking-resistant). Our findings indicate that nectarine fruit-cracking occurs during the second stage of fruit expansion. Despite no differences in epicarp cell size between "Qiannianhong" and "CR1012", the mesocarp cells of "Qiannianhong" were larger than those of "CR1012". Moreover, a comparison of starch hydrolysis between the two varieties revealed that "CR1012" had higher starch content in the mesocarp but lower soluble sugar content compared to "Qiannianhong". Additionally, by testing the α-amylase and ß-amylase activity of the mesocarp, our results showed a difference only in α-amylase activity between the two varieties. Furthermore, qRT-PCR detection indicated a higher expression level of the PpAmy1 (α-amylase synthesis gene) in "Qiannianhong" compared to "CR1012". To further investigate the role of PpAmy1, we employed RNAi technology to suppress its expression in "Qiannianhong" fruits. The results showed a significant reduction in α-amylase activity, starch hydrolysis, soluble sugar content, cell size of the mesocarp, and fruit-cracking. These findings underscore the pivotal role of PpAmy1 in the occurrence of nectarine fruit cracking.


Assuntos
Frutas , Amido , Amido/metabolismo , Frutas/metabolismo , Hidrólise , Açúcares/metabolismo , alfa-Amilases/metabolismo
6.
Bioorg Chem ; 143: 107085, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38183681

RESUMO

A green catalyst WELPSA-catalyzed three-component condensation (Biginelli) process involving an aldehyde, barbituric/thiobarbituric/1,3-dimethylbarbituric acid, and urea/thiourea/guanidine hydrochloride in a single pot in presence of a green solvent for the production of DHPM have been presented. The catalyst is reusable and this methodology is scalable. By using the in vitro experiments, the antidiabetic potentiality of synthesized compounds that inhibit α-amylase along with α-glucosidase efficiencies was assessed. All the synthesized compounds except for 4a and 4e, showed the most significant inhibition for α-amylase and α-glucosidase activities. Among the synthesized DHPM compounds, 4c and 4b exhibited significant inhibition profiles compared to the standard antidiabetic drug acarbose. Furthermore, synthesized substances' energy-minimized structures, 3D structures, and DFT calculations were performed using Gaussian 09 software, hybrid models, and MM2 force approaches. Strong hydrogen bonds with amino acid residues Arg-672, Arg-600, Trp-613, Asp-404, Asp-282, and Asp-616 indicate that an α-glucosidase-inhibitory peptide may have hypoglycemic efficacy confirmed by the molecular docking study of the synthesized DHPM.


Assuntos
Inibidores de Glicosídeo Hidrolases , alfa-Glucosidases , Inibidores de Glicosídeo Hidrolases/química , Simulação de Acoplamento Molecular , alfa-Glucosidases/metabolismo , alfa-Amilases/metabolismo , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Catálise
7.
Sci Rep ; 14(1): 1312, 2024 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-38225280

RESUMO

In this study, a two pyrazole derivatives; 2-(5-methyl-1H-pyrazole-3-carbonyl)-N-phenylhydrazine-1-carboxamide (Pyz-1) and 4-amino-5-(5-methyl-1H-pyrazol-3-yl)-4H-1,2,4-triazole-3-thiol (Pyz-2) were synthesized and characterized by 13C-NMR, 1H-NMR, FT-IR, and mass spectrometry. A complete molecular structures optimization, electronic and thermodynamic properties of Pyz-1 and Pyz-2 in gas phase and aqueous solution were predicted by using hybrid B3LYP method with the 6-311++G** basis sets. Pyz-1 and Pyz-2 were evaluated in vitro for their anti-diabetic, antioxidant and xanthine oxidase inhibition activities. For anti-diabetic activity, Pyz-1 and Pyz-2 showed a potent α-glucosidase and α-amylase inhibition with IC50 values of 75.62 ± 0.56, 95.85 ± 0.92 and 119.3 ± 0.75, 120.2 ± 0.68 µM, respectively, compared to Acarbose (IC50(α-glucosidase) = 72.58 ± 0.68 µM, IC50(α-amylase) = 115.6 ± 0.574 µM). In xanthine oxidase assay, Pyz-1 and Pyz-2 exhibited remarkable inhibitory ability with IC50 values 24.32 ± 0.78 and 10.75 ± 0.54 µM, respectively. The result of antioxidant activities showed that the title compounds have considerable antioxidant and radical scavenger abilities. In addition, molecular docking simulation was used to determine the binding modes and energies between the title compounds and α-glucosidase and α-amylase enzymes.


Assuntos
Diabetes Mellitus , Hipoglicemiantes , Humanos , Hipoglicemiantes/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Antioxidantes/farmacologia , Antioxidantes/química , Simulação de Acoplamento Molecular , alfa-Glucosidases/metabolismo , Xantina Oxidase , Espectroscopia de Infravermelho com Transformada de Fourier , Estrutura Molecular , Pirazóis/farmacologia , alfa-Amilases/metabolismo , Relação Estrutura-Atividade
8.
Bioorg Chem ; 143: 107068, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38181659

RESUMO

α-Amylase is a secretory enzyme commonly found in nature. The α-Amylase enzyme catalyzes the hydrolysis of α-D-(1,4)-glucosidic bonds in starch, glycogen, and polysaccharides. The chemical characterization of the composite carrier and the immobilized enzyme was performed, and the accuracy of the immobilization was confirmed by FTIR, SEM, and EDS analyses. The X-ray diffraction (XRD) analysis indicates that the magnetic nanoparticle retained its magnetic properties following the modification process. Based on the Thermogravimetric Analysis (TGA) outcomes, it was evident that the structural integrity of the FPT nanocomposite remained unchanged at 200°C. The optimal pH was determined to be 5.5, and no alteration was observed following the immobilization process. Purified α-amylases usually lose their activity rapidly above 50°C. In this study, Bacillus licheniformis α-Amylase enzyme was covalently immobilized on the newly synthesized magnetic composite carrier having more azole functional group. For novelty-designed immobilized enzymes, while there is no change in the pH and optimum operating temperature of the enzyme with immobilization, two essential advantages are provided to reduce enzyme costs: the storage stability and reusability are increased. Furthermore, our immobilization technique enhanced enzyme stability when comparing our immobilized enzyme with the reference enzyme in industrial applications. The activity of the immobilized enzyme was higher in presence of 1-3% H2O2.


Assuntos
Bacillus licheniformis , Compostos de Epóxi , Nanopartículas de Magnetita , Metacrilatos , Triazóis , Enzimas Imobilizadas/química , Bacillus licheniformis/metabolismo , Peróxido de Hidrogênio , Nanopartículas de Magnetita/química , Concentração de Íons de Hidrogênio , Estabilidade Enzimática , alfa-Amilases/metabolismo , Temperatura
9.
Sci Rep ; 14(1): 1919, 2024 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-38253703

RESUMO

The use of traditional herbal remedies has been a common practice for centuries across different cultures to treat various ailments. In Palestine, traditional herbal medicines are widely used, but their efficacy and safety have not been thoroughly investigated. Therefore, the purpose of this study was to assess the biological activity and toxicity of two traditional herbal blends often used to treat obesity in the West Bank region of Palestine. Two herbal blends with a total of eight plants were chosen based on their historic use and availability. The plant aqueous extracts were evaluated for their antioxidant, anti-fibrotic, anti-obesity, anti-diabetic, and cytotoxic activities. The results showed that these blends have potent antifibrotic, antioxidant, and anticancer activities. While their activities on α-amylase and lipase enzymes (main targets) showed moderate activities. Therefore, our results showed that Herbal Blend 2 was more potent than Herbal Blend 1 on all investigated targets. Herbal Blend 2 showed significant activities as an antioxidant, antifibrotic, and anticancer activities with IC50 values of 68.16 ± 2.45, 33.97 ± 1.14, and 52.53 ± 0.78 µg/mL against DPPH, LX-2, and MCF-7 cell lines, respectively. While it is IC50 values on α-amylase and lipase enzymes were 243.73 ± 1.57 and 1358.39 ± 2.04 µg/mL, respectively. However, the use of anti-cancer plants can be challenging due to their cytotoxic effects on the body. We urge individuals to exercise caution when using natural remedies and to seek medical advice before incorporating them into their health regimens. This study provides valuable insight into the potential health benefits of traditional herbal remedies and emphasizes the importance of responsible usage.


Assuntos
Antioxidantes , Árabes , Humanos , Antioxidantes/farmacologia , Lipase , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , alfa-Amilases
10.
Molecules ; 29(2)2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38257312

RESUMO

Ligustrum vulgare (LV), widely cultivated in Europe and often used in hedges, has been historically recognized in folk medicine for its potential health benefits. This study focused on exploring the untargeted identification of secondary metabolites in ethanol extracts (70% v/v) from different morphological parts (young shoots, leaves, flowers and fruits) of LV at various stages of plant development, using ultra-high-performance liquid chromatography with high-resolution mass spectrometry (UHPLC-HRMS). Additionally, the selected biological activities (antioxidant activity, cyclooxygenase-2 inhibition (COX-2), α-amylase inhibition and cytotoxicity) of the tested extracts were determined. Untargeted metabolomics showed that LV extracts were a rich source of phenylethanoid compounds, flavonoids, iridoids and their derivatives. The flowers of LV had the highest content of oleuropein (33.43 ± 2.48 mg/g d.w.). The lowest antioxidant activity was obtained for ripe and post-seasonal fruits, while in the case of other samples, the activity was at a similar level. All tested extracts showed α-amylase and COX-2 inhibitory activity. In addition, LV extracts showed strong antiproliferative properties in colorectal (HT29) and liver (HepG2) cancer cell lines. The obtained results show the difference in the content of bioactive compounds in various morphological parts of Ligustrum vulgare. These differences may influence the multifaceted medicinal potential of this plant.


Assuntos
Antioxidantes , Ligustrum , Antioxidantes/farmacologia , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Ciclo-Oxigenase 2 , alfa-Amilases
11.
Molecules ; 29(2)2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38257308

RESUMO

α-Amylase inhibitory peptides are used to treat diabetes, but few studies have statistically characterized their interaction with α-amylase. This study performed the molecular docking of α-amylase with inhibitory peptides from published papers. The key sites, side chain chargeability, and hydrogen bond distribution characteristics were analyzed. Molecular dynamics simulated the role of key sites in complex stability. Moreover, partial least squares regression (PLSR) was used to analyze the contribution of different amino acids in the peptides to inhibition. The results showed that, for the α-amylase molecule, His201 and Gln63, with the highest interaction numbers (INs, 15, 15) and hydrogen bond values (HBVs, 11.50, 10.33), are the key sites on α-amylase, and amino acids with positively charged side chains were important for inhibitory activity. For the inhibitory peptides, Asp and Arg had the highest HBVs, and amino acids with charged side chains were more likely to form hydrogen bonds and exert inhibitory activity. In molecular dynamics simulations, peptides involving key binding sites formed more stable complexes with α-amylase than α-amylase alone, suggesting enhanced inhibitory effects. Further, PLSR results showed that amino acids close to the N-terminus of the inhibitory peptide, located in the third and fifth positions, were significantly correlated with its inhibitory activity. In conclusion, this study provides a new approach to developing and screening α-amylase inhibitors.


Assuntos
Antifibrinolíticos , alfa-Amilases , Simulação de Acoplamento Molecular , Análise dos Mínimos Quadrados , Simulação de Dinâmica Molecular , Aminoácidos , Peptídeos
12.
Mar Drugs ; 22(1)2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-38248660

RESUMO

In extreme environments such as Antarctica, a diverse range of organisms, including diatoms, serve as essential reservoirs of distinctive bioactive compounds with significant implications in pharmaceutical, cosmeceutical, nutraceutical, and biotechnological fields. This is the case of the new species Craspedostauros ineffabilis IMA082A and Craspedostauros zucchellii IMA088A Trentin, Moschin, Lopes, Custódio and Moro (Bacillariophyta) that are here explored for the first time for possible biotechnological applications. For this purpose, a bioprospection approach was applied by preparing organic extracts (acetone and methanol) from freeze-dried biomass followed by the evaluation of their in vitro antioxidant properties and inhibitory activities on enzymes related with Alzheimer's disease (acetylcholinesterase: AChE, butyrylcholinesterase: BChE), Type 2 diabetes mellitus (T2DM, α-glucosidase, α-amylase), obesity (lipase) and hyperpigmentation (tyrosinase). Extracts were then profiled by ultra-high-performance liquid chromatography-mass spectrometry (UPLC-HR-MS/MS), while the fatty acid methyl ester (FAME) profiles were established by gas chromatography-mass spectrometry (GC-MS). Our results highlighted strong copper chelating activity of the acetone extract from C. ineffabilis and moderate to high inhibitory activities on AChE, BChE, α-amylase and lipase for extracts from both species. The results of the chemical analysis indicated polyunsaturated fatty acids (PUFA) and their derivatives as the possible compounds responsible for the observed activities. The FAME profile showed saturated fatty acids (SFA) as the main group and methyl palmitoleate (C16:1) as the predominant FAME in both species. Overall, our results suggest both Antarctic strains as potential sources of interesting molecules with industrial applications. Further studies aiming to investigate unidentified metabolites and to maximize growth yield and natural compound production are required.


Assuntos
Diabetes Mellitus Tipo 2 , Diatomáceas , Humanos , Regiões Antárticas , Acetona , Acetilcolinesterase , Butirilcolinesterase , Cromatografia Gasosa-Espectrometria de Massas , Espectrometria de Massas em Tandem , Ácidos Graxos , Lipase , alfa-Amilases
13.
Sci Rep ; 14(1): 2499, 2024 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-38291095

RESUMO

Diabetes is a serious health issue that can be a great risk factor related to numerous physical problems. A class of drugs "Gliflozin" especially Sodium Glucose Co. Transporter 2 was inhibited by a novel drug, which is known as "empagliflozin". While ZnO nanoparticles (NPs) had considerable promise for combating diabetes, it was employed in the treatment and management of type-2 diabetes mellitus. The new drug empagliflozin was initially incorporated into Zinc Oxide NPs in this study using the surface physio-sorption technique, and the degree of drug adsorption was assessed using the HPLC method. The tailored product was characterized by using the FTIR, EDX, Ultraviolet-Visible, XRD and SEM techniques. With an average particle size of 17 nm, SEM revealed mono-dispersion of NPs and sphere-like form. The Freundlich isotherm model best fits and explains the data for the physio-sorption investigation, which examined adsorption capabilities using adsorption isotherms. The enzymes α-amylase and α-glucosidase, which are involved in the human metabolism of carbohydrates, were used in the in-vitro anti-diabetic assays. It was discovered that the composite showed the highest levels of 81.72 and 92.77% inhibition of -α-amylase and -glucosidase at an absolute concentration of 1000 µg per ml with IC50 values of 30.6 µg per ml and 72 µg per ml.


Assuntos
Compostos Benzidrílicos , Diabetes Mellitus Tipo 2 , Glucosídeos , Nanopartículas Metálicas , Nanopartículas , Óxido de Zinco , Humanos , Óxido de Zinco/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , alfa-Amilases , Antibacterianos/farmacologia , Extratos Vegetais
14.
Planta ; 259(2): 40, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38265531

RESUMO

MAIN CONCLUSION: Genetic loci, particularly those with an effect in the independent panel, could be utilised to further reduce LMA expression when used with favourable combinations of genes known to affect LMA. Late maturity α-amylase (LMA) is a grain quality defect involving elevated α-amylase within the aleurone of wheat (Triticum aestivum L.) grains. The genes known to affect expression are the reduced height genes Rht-B1 (chromosome 4B) and Rht-D1 (chromosome 4D), and an ent-copalyl diphosphate synthase gene (LMA-1) on chromosome 7B. Other minor effect loci have been reported, but these are poorly characterised and further genetic understanding is needed. In this study, twelve F4-derived populations were created through single seed descent, genotyped and evaluated for LMA. LMA-1 haplotype C and the Rht-D1b allele substantially reduced LMA expression. The alternative dwarfing genes Rht13 and Rht18 had no significant effect on LMA expression. Additional quantitative trait loci (QTL) were mapped at 16 positions in the wheat genome. Effects on LMA expression were detected for four of these QTL in a large independent panel of Australian wheat lines. The QTL detected in mapping populations and confirmed in the large independent panel provide further opportunity for selection against LMA, especially if combined with Rht-D1b and/or favourable haplotypes of LMA-1.


Assuntos
Triticum , alfa-Amilases , Austrália , Locos de Características Quantitativas , Alelos
15.
PLoS One ; 19(1): e0297434, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38289914

RESUMO

This study aimed to obtain a high yield and purity of Sargassum pallidum polyphenol extracts (SPPE) and study its enzyme activity. Fresh Sargassum pallidum seaweed was selected for optimization of ultrasound-assisted extraction (UAE) conditions and purification conditions using macroporous resin and Sephadex LH20 to obtain SPPE. The SPPE was characterized using UPLC-QTOF-MS/MS and α-amylase, α-glucosidase, tyrosinase, and AchE inhibitory activity were determined. The maximum extraction rate of SPPE was 7.56 mg GAE/g and the polyphenol purity reached 70.5% after macroporous resin and Sephadex LH-20 purification. A total of 50 compounds were identified by UPLC-QTOF-MS/MS. The IC50 values of SPPE were 334.9 µg/mL, 6.290 µg /mL, 0.834 mg /mL and 0.6538 mg /mL for α-amylase, α-glucosidase, tyrosinase and AchE, respectively. Molecular docking technology further revealed the effects of SPPE on the above enzymes. This study provided information on the potential hypoglycemic, whitening and anti-Alzheimer's disease biological activities of SPPE, which had guiding significance for the purification and development of other seaweed polyphenols.


Assuntos
Polifenóis , Sargassum , Polifenóis/farmacologia , Simulação de Acoplamento Molecular , Monofenol Mono-Oxigenase/metabolismo , alfa-Glucosidases/metabolismo , Espectrometria de Massas em Tandem , Globo Pálido , alfa-Amilases/metabolismo , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia
16.
BMC Complement Med Ther ; 24(1): 65, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38291462

RESUMO

BACKGROUND: Type 2 Diabetes mellitus (DM) is an affliction impacting the quality of life of millions of people worldwide. An approach used in the management of Type 2 DM involves the use of the carbohydrate-hydrolyzing enzyme inhibitor, acarbose. Although acarbose has long been the go-to drug in this key approach, it has become apparent that its side effects negatively impact patient adherence and subsequently, therapeutic outcomes. Similar to acarbose in its mechanism of action, bee propolis, a unique natural adhesive biomass consisting of biologically active metabolites, has been found to have antidiabetic potential through its inhibition of α-amylase. To minimize the need for ultimately novel agents while simultaneously aiming to decrease the side effects of acarbose and enhance its efficacy, combination drug therapy has become a promising pharmacotherapeutic strategy and a focal point of this study. METHODS: Computer-aided molecular docking and molecular dynamics (MD) simulations accompanied by in vitro testing were used to mine novel, pharmacologically active chemical entities from Egyptian propolis to combat Type 2 DM. Glide docking was utilized for a structure-based virtual screening of the largest in-house library of Egyptian propolis metabolites gathered from literature, in addition to GC-MS analysis of the propolis sample under investigation. Thereafter, combination analysis by means of fixed-ratio combinations of acarbose with propolis and the top chosen propolis-derived phytoligand was implemented. RESULTS: Aucubin, identified for the first time in propolis worldwide and kaempferol were the most promising virtual hits. Subsequent in vitro α-amylase inhibitory assay demonstrated the ability of these hits to significantly inhibit the enzyme in a dose-dependent manner with an IC50 of 2.37 ± 0.02 mM and 4.84 ± 0.14 mM, respectively. The binary combination of acarbose with each of propolis and kaempferol displayed maximal synergy at lower effect levels. Molecular docking and MD simulations revealed a cooperative binding mode between kaempferol and acarbose within the active site. CONCLUSION: The suggested strategy seems imperative to ensure a steady supply of new therapeutic entities sourced from Egyptian propolis to regress the development of DM. Further pharmacological in vivo investigations are required to confirm the potent antidiabetic potential of the studied combination.


Assuntos
Diabetes Mellitus Tipo 2 , Própole , Humanos , Acarbose/farmacologia , Acarbose/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Quempferóis , Própole/farmacologia , Simulação de Acoplamento Molecular , Diabetes Mellitus Tipo 2/tratamento farmacológico , Egito , Qualidade de Vida , alfa-Glucosidases/metabolismo , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , alfa-Amilases/metabolismo
17.
Eur J Med Chem ; 266: 116139, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38252989

RESUMO

Diabetes is one of the fastest-growing metabolic disorders, nearly doubling the number of patients each year. There are different treatment approaches available for the management of diabetes, which lacks due to their side effects. The inhibition of enzymes involved in the metabolism of complex polysaccharides to monosaccharides has proven beneficial in patients with type 2 diabetes mellitus. Two enzymes, α-amylase and α-glucosidase, have emerged as potential drug targets and are widely explored for drug development against type 2 diabetes mellitus. In this context, thiazolidine-2,4-diones (TZDs) have emerged as potential drug candidates for developing newer molecules against α-amylase and α-glucosidase. Nineteen TZD-hybrids were synthesized and evaluated in vitro α-amylase and α-glucosidase inhibitory activity. The compounds 7i, 7k, and 7p have emerged as the best dual inhibitors with IC50 of 10.33 ± 0.11-20.94 ± 0.76 µM and 10.19 ± 0.25-24.07 ± 1.56 µM against α-glucosidase and α-amylase, respectively. The derivatives had good anti-oxidant activity, displaying IC50 = 14.95 ± 0.65-23.27 ± 0.99 µM. The compounds 7k and 7p showed the best inhibition of reactive oxygen species in the PNAC-1 cells. The molecules exhibit good binding within the active site of α-amylase (PDB id: 1B2Y) and α-glucosidase (PDB id: 3W37), displaying binding energies of -7.5 to -10.7 kcal/mol and -7.4 to -10.3 kcal/mol, respectively. Further, the compounds were nontoxic (LD50 = 500-1311 mg/kg) and possessed good GI absorption. The compounds 7i, 7k, and 7p were evaluated in vivo antidiabetic activity in an STZ-induced diabetic model in Wistar rats. The compound 7p emerged as the best compound in the in vivo studies; however, the activity was lesser than that of the standard drug pioglitazone.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Tiazolidinedionas , Humanos , Ratos , Animais , Hipoglicemiantes/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Tiazolidinas/uso terapêutico , alfa-Glucosidases/metabolismo , Simulação de Acoplamento Molecular , Ratos Wistar , alfa-Amilases , Inibidores de Glicosídeo Hidrolases/química
18.
Sci Rep ; 14(1): 481, 2024 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-38177253

RESUMO

Using PEG-based deep eutectic solvents (PDES), the current study proposes extractive fermentation as a sustainable process integration for the production and purification of α-amylase from Bacillus simplex (ON754233). Glucose: PEG 400 outperformed five PDES in terms of tie lie length (58) and slope value (1.23) against sodium sulphatt. Apple cider pomace was used as a low-cost, sustainable carbon source to produce-amylase, with a maximum enzyme production of 2200.13 U/mL. PDES concentration (20% w/v), salt (12.75 w/v), and apple waste (2.75 g/mL) were all optimized using response surface methodology. When scaled upto 3 L benchtop bioreactor, extractive fermentation was proved to be better technology with maximum recovery of 92.4% with highest partition coefficient (3.59). The partially purified enzyme was further purified using a Sephadex G 100 followed by DEAE-Sephadex anion exchange chromatography with a purity fold of 33. The enzyme was found to be thermostable at the temperature (60 °C), remains alkaline (pH 8), and the activity was stimulated in the presence of Mg2+ ions. With SDS PAGE electrophoresis, the molecular weight was found to be around 140 kDa. Finally, the enzyme kinetics parameters were evaluated with observed Km (0.00396 mM) and Vmax (37.87 U/mL). Thus scaling up extractive fermentation entails increasing production capacity with improved extraction efficiency using green solvents.


Assuntos
Solventes Eutéticos Profundos , alfa-Amilases , alfa-Amilases/metabolismo , Solventes/química , Fermentação , Concentração de Íons de Hidrogênio , Temperatura , Estabilidade Enzimática
19.
Molecules ; 29(2)2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-38257218

RESUMO

Isoxazolidine derivatives were designed, synthesized, and characterized using different spectroscopic techniques and elemental analysis and then evaluated for their ability to inhibit both α-amylase and α-glucosidase enzymes to treat diabetes. All synthesized derivatives demonstrated a varying range of activity, with IC50 values ranging from 53.03 ± 0.106 to 232.8 ± 0.517 µM (α-amylase) and from 94.33 ± 0.282 to 258.7 ± 0.521 µM (α-glucosidase), revealing their high potency compared to the reference drug, acarbose (IC50 = 296.6 ± 0.825 µM and 780.4 ± 0.346 µM), respectively. Specifically, in vitro results revealed that compound 5d achieved the most inhibitory activity with IC50 values of 5.59-fold and 8.27-fold, respectively, toward both enzymes, followed by 5b. Kinetic studies revealed that compound 5d inhibits both enzymes in a competitive mode. Based on the structure-activity relationship (SAR) study, it was concluded that various substitution patterns of the substituent(s) influenced the inhibitory activities of both enzymes. The server pkCSM was used to predict the pharmacokinetics and drug-likeness properties for 5d, which afforded good oral bioavailability. Additionally, compound 5d was subjected to molecular docking to gain insights into its binding mode interactions with the target enzymes. Moreover, via molecular dynamics (MD) simulation analysis, it maintained stability throughout 100 ns. This suggests that 5d possesses the potential to simultaneously target both enzymes effectively, making it advantageous for the development of antidiabetic medications.


Assuntos
alfa-Amilases , alfa-Glucosidases , Cinética , Simulação de Acoplamento Molecular , Disponibilidade Biológica
20.
Molecules ; 29(2)2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38257240

RESUMO

The present study evaluated the antioxidant and antidiabetic properties of Medicago sativa and Solidago virgaurea extracts enriched in polyphenolic compounds. The extracts were obtained by accelerated solvent extraction (ASE) and laser irradiation. Then, microfiltration was used for purification, followed by nanofiltration used to concentrate the two extracts. The obtained extracts were analyzed to determine their antioxidant activity using DPPH radical scavenging and reducing power methods. The antidiabetic properties have been investigated in vitro on a murine insulinoma cell line (ß-TC-6) by the inhibition of α-amylase and α-glucosidase. M. sativa obtained by laser irradiation and concentrated by nanofiltration showed the highest DPPH• scavenging (EC50 = 105.2 ± 1.1 µg/mL) and reducing power activities (EC50 = 40.98 ± 0.2 µg/mL). M. sativa extracts had higher inhibition on α-amylase (IC50 = 23.9 ± 1.2 µg/mL for concentrated extract obtained after ASE, and 26.8 ± 1.1), while S. virgaurea had the highest α-glucosidase inhibition (9.3 ± 0.9 µg/mL for concentrated extract obtained after ASE, and 8.6 ± 0.7 µg/mL for concentrated extract obtained after laser extraction). The obtained results after evaluating in vitro the antidiabetic activity showed that the treatment with M. sativa and S. virgaurea polyphenolic-rich extracts stimulated the insulin secretion of ß-TC-6 cells, both under normal conditions and under hyperglycemic conditions as well. This paper argues that M. sativa and S. virgaurea polyphenolic-rich extracts could be excellent natural sources with promising antidiabetic potential.


Assuntos
Neoplasias Pancreáticas , Solidago , Animais , Camundongos , Antioxidantes/farmacologia , Medicago sativa , alfa-Glucosidases , Hipoglicemiantes/farmacologia , alfa-Amilases , Extratos Vegetais/farmacologia
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