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1.
Int J Nanomedicine ; 14: 4741-4754, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456635

RESUMO

Background: Ipomoea batatas (L.) Lam.(Ib) has high content of various beneficial nutrients which helps in improving and maintaining human health. It is well known as a functional food and also a valuable source of unique natural products. It contains various phenolic and flavonoid bioactive compounds. Methods: In this study, using the outer peel of two varieties of Ib : Korean red skin sweet potato and Korean pumpkin sweet potato, silver nanoparticles (AgNPs) were synthesized (termed Ib1-AgNps and Ib2-AgNps), respectively. Characterization of Ib1-AgNPs and Ib2-AgNPs was carried out through scanning electron microscopy, Fourier-transform infrared (FT-IR) spectroscopy, energy-dispersive X-ray analysis, X-ray powder diffraction and UV-Vis spectroscopy. Further, the bio-potential of the synthesized AgNPs was investigated by antidiabetic (α-glucosidase assay), antioxidant (free radical scavenging assays), antibacterial (disc diffusion method) and cytotoxicity assays (cell viability against HepG2 cells). Results: FT-IR spectroscopy revealed the contribution of bioactive compounds existing in Ib1 and Ib2 extracts, in the biosynthesis and equilibrium of the AgNPs. Although the Ib2-AgNPs had a higher atomic percentage of Ag in comparison with Ib1-AgNPs, in the antidiabetic assay, the inhibition percentage of α-glucosidase was higher for AgNPs of Ib1 than Ib2, at all three concentrations examined. From the cytotoxicity results, HepG2 cancer cells were more sensitive to the Ib1-AgNPs in comparison to the Ib2-AgNPs-treated HepG2 cells. The antioxidant prospective was higher in Ib2-AgNPs than Ib1-AgNPs. Moreover, the Ib2-AgNPs showed inhibitory action against all five tested pathogenic bacteria, producing an inhibition zone of 8.74-11.52 mm while Ib1-AgNPs had an inhibitory effect on four of them, with an 8.67-11.23 (mm) inhibition zone. Conclusions: Overall, the results concluded that the Ib2-AgNPs exhibited relatively higher functional activity than Ib1-AgNPs, which might be credited to the greater abundance of bioactive compounds existing in Ib2 extract that acted as reducing as well as capping agents in the synthesis of Ib2-AgNPs. Overall, the current study highlights a novel cost-effective and eco-friendly AgNPs synthesis using food waste peels with biocompatibility and could be potentially utilized in biomedical and pharmaceutical industries.


Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Ipomoea batatas/química , Nanopartículas Metálicas/química , Prata/farmacologia , Bactérias/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Células Hep G2 , Humanos , Hipoglicemiantes/farmacologia , Concentração Inibidora 50 , Nanopartículas Metálicas/ultraestrutura , Testes de Sensibilidade Microbiana , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X , alfa-Glucosidases/metabolismo
2.
J Agric Food Chem ; 67(37): 10521-10533, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31461284

RESUMO

This work was designed to comparatively investigate 27 dietary flavonoids that act as α-glucosidase inhibitors and insulin sensitizers. On the basis of the results of an in vitro experiment of α-glucosidase inhibition, myricetin (IC50 = 11.63 ± 0.36 µM) possessed the strongest inhibitory effect, followed by apigenin-7-O-glucoside (IC50 = 22.80 ± 0.24 µM) and fisetin (IC50 = 46.39 ± 0.34 µM). A three-dimensional quantitative structure-activity relationship model of α-glucosidase inhibitors with good predictive capability [comparative molecular field analysis, q2 = 0.529, optimum number of components (ONC) = 10, R2 = 0.996, F = 250.843, standard error of estimation (SEE) = 0.064, and two descriptors; comparative similarity index analysis, q2 = 0.515, ONC = 10, R2 = 0.997, F = 348.301, SEE = 0.054, and four descriptors] was established and indicated that meta positions of ring B favored bulky and minor, electron-withdrawing, and hydrogen bond donor groups. The presence of electron-donating and hydrogen bond acceptor groups at position 4' of ring B could improve α-glucosidase activity. Position 3 of ring C favored minor, electron-donating, and hydrogen bond donor groups, whereas position 7 of ring A favored bulky and hydrogen bond acceptor groups. Molecular docking screened five flavonoids (baicalein, isorhamnetin-3-O-rutinoside, apigenin-7-O-glucoside, kaempferol-7-O-ß-glucoside, and cyanidin-3-O-glucoside) that can act as insulin sensitizers and form strong combinations with four key protein targets involved in the insulin signaling pathway. Apigenin-7-O-glucoside (60 µM) can effectively improve insulin resistance, and glucose uptake increased by approximately 73.06% relative to the model group of insulin-resistant HepG2 cells. Therefore, apigenin-7-O-glucoside might serve as the most effective α-glucosidase inhibitor and insulin sensitizer. This work may guide diabetes patients to improve their condition through dietary therapy.


Assuntos
Flavonoides/química , Inibidores de Glicosídeo Hidrolases/química , Insulina/metabolismo , Flavonoides/metabolismo , Flavonoides/farmacologia , Inibidores de Glicosídeo Hidrolases/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Células Hep G2 , Humanos , Simulação de Acoplamento Molecular , Saccharomyces cerevisiae/enzimologia , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismo , alfa-Glucosidases/química , alfa-Glucosidases/metabolismo
3.
Food Chem ; 298: 125026, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31260961

RESUMO

Roasted cotyledons of the Chilean hazelnut (Gevuina avellana) are appreciated as snacks. The aim of our work was to assess the fatty acid, oxylipin and phenolic composition using gas chromatography (GC) coupled to mass spectrometry (MS), ultra- high performance liquid chromatography (UHPLC) coupled to MS and HPLC coupled to diode array detector (HPLC-DAD). Additionally, various antioxidant activities were assessed. The inhibition of α-glucosidase, α-amylase, lipase, cyclooxygenases-1 and -2 (COX-1/COX-2), and lipoxygenase was determined. The main fatty acids were oleic and 7-hexadecenoic acids. Eight phytoprostanes and three phytofurans were identified and quantified. Hydroxybenzoic and hydroxycinnamic acids were the main phenolic compounds. Oils showed antioxidant activity determined by EPR, and inhibition of COX-1/COX-2. The statistical analysis showed that the roasting does not affect the composition of the samples. The occurrence of oxylipins in this species is reported for the first time. Chilean hazelnuts can be considered a source of health promoting compounds.


Assuntos
Antioxidantes/química , Corylus/química , Síndrome Metabólica/enzimologia , Oxilipinas/análise , Fenóis/análise , Chile , Ácidos Cumáricos/análise , Cromatografia Gasosa-Espectrometria de Massas , alfa-Amilases/antagonistas & inibidores , alfa-Glucosidases/metabolismo
4.
J Agric Food Chem ; 67(32): 8986-8993, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31347835

RESUMO

Trehalose plays a crucial role in response to freezing stress in baker's yeast. MAL62, a gene involved in the adenosine diphosphoglucose-dependent trehalose synthesis pathway, can increase trehalose content. However, the difference between MAL62-related trehalose synthesis and traditional uridine diphosphoglucose-dependent trehalose synthesis is not well-understood. MAL62 overexpression showed less effect in enhancing intracellular trehalose compared to TPS1 overexpression. However, MAL62 overexpression elicited trehalose synthesis before fermentation with enhanced maltose metabolism and had a similar effect on cell viability after freezing. Furthermore, MAL62 and TPS1 overexpression in the NTH1 deletion background further strengthened freezing tolerance and improved leavening ability. Our results suggest that the enhancement in freezing tolerance by MAL62 overexpression may involve multiple pathways rather than simply enhancing trehalose synthesis. The results reveal valuable insights into the relationship between maltose metabolism and freezing tolerance and may help to develop better yeast strains for enhancing fermentation characteristics of frozen dough.


Assuntos
Glucosiltransferases/metabolismo , Maltose/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/enzimologia , Saccharomyces cerevisiae/genética , alfa-Glucosidases/metabolismo , Farinha/análise , Farinha/microbiologia , Congelamento , Regulação Fúngica da Expressão Gênica , Glucosiltransferases/genética , Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genética , Trealase/genética , Trealase/metabolismo , Trealose/metabolismo , alfa-Glucosidases/genética
5.
Plant Foods Hum Nutr ; 74(3): 430-435, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31302831

RESUMO

The beneficial health effects of apple consumption are well known, however, little is known about the potential of its phenolic fractions to inhibit α-glucosidases and thereafter to treat diseases related to the carbohydrate metabolism, such as postprandial hyperglycemia and diabetes. In the present study, the α-glucosidase inhibition and antioxidant activity of different phenolic fractions of apple were evaluated using the 2,2-diphenyl-1-picrylhydrazyl and hydroxyl radical scavenging activity. Moreover, the phenolic fractions were chemically characterized by LC-MS in order to identify the compounds responsible for the biological properties. The purified extract (not fractionated) had the highest α-glucosidase and hydroxyl radical inhibitions. The purified extract and fractions III and IV were more active against the enzyme activity than the positive control acarbose, the drug used by diabetic patients to treat postprandial hyperglycaemia. Our results show that apple phenolic extracts strongly inhibit α-glucosidase acitivity, validating their potential to be used in the management of type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores de Glicosídeo Hidrolases/farmacologia , Hiperglicemia/tratamento farmacológico , Malus/química , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Metabolismo dos Carboidratos , Fenóis/isolamento & purificação , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/isolamento & purificação , alfa-Glucosidases/metabolismo
6.
J Agric Food Chem ; 67(31): 8617-8625, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31293160

RESUMO

Inhibiting starch digestion can effectively control postprandial blood sugar level. In this study, the in vitro digestion differences among the mixtures of five polyphenols (i.e., procyanidins [PAs], catechin [CA], tannic acid [TA], rutin [RU], and quercetin [QU]) and starch were analyzed through an in vitro simulation test of starch digestion. The interaction characteristics of these five polyphenols with α-amylase and α-glucosidase were investigated in terms of the inhibition effect, dynamics, fluorescence quenching, and circular dichroism (CD). The results revealed that the rapidly digestible starch (RDS) contents decreased, while the resistant starch (RS) contents increased. All five polyphenols inhibited the α-amylase activity through the noncompetitive approach but inhibited the α-glucosidase activity through the competitive approach. Five polyphenols combined with α-amylase spontaneously by using the hydrophobic effect. The interaction of PAs and QU with α-glucosidase were recognized as van der Waals forces and H bonding, whereas CA and TA interacted with α-glucosidase through the hydrophobic effect. All five polyphenols can cause conformational changes in enzymes.


Assuntos
Extratos Vegetais/química , Polifenóis/química , Amido/química , Animais , Digestão , Inibidores Enzimáticos/química , Inibidores Enzimáticos/metabolismo , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Cinética , Modelos Biológicos , Extratos Vegetais/metabolismo , Polifenóis/metabolismo , Amido/metabolismo , Suínos , Leveduras/enzimologia , alfa-Amilases/química , alfa-Amilases/metabolismo , alfa-Glucosidases/química , alfa-Glucosidases/metabolismo
7.
Chem Biodivers ; 16(8): e1900183, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31361076

RESUMO

This work describes the study of the chemical composition and bioactivity of the essential oils (EOs) of the different organs (leaves, flowers, stems and roots) from Eruca vesicaria. According to the GC and GC/MS analysis, all the EOs were dominated by erucin (4-methylthiobutyl isothiocyanate) with a percentage ranging from 17.9 % (leaves) to 98.5 % (roots). The isolated EOs were evaluated for their antioxidant (DPPH, ABTS and ß-carotene/linoleic acid), antibacterial and inhibitory property against α-amylase and α-glucosidase. Most EOs exhibited an interesting α-glucosidase and α-amylase inhibitory potential. The roots essential oil was found to be the most active with IC50 values of 0.80±0.06 and 0.11±0.01 µg mL-1 , respectively. The essential oil of roots exhibited the highest antioxidant activity (DPPH, PI=92.76±0.01 %; ABTS, PI=78.87±0.19; and ß-carotene, PI=56.1±0.01 %). The isolated oils were also tested for their antibacterial activity against two Gram-positive and three Gram-negative bacteria. Moderate results have been noted by comparison with Gentamicin used as positive control.


Assuntos
Antioxidantes/química , Brassicaceae/metabolismo , Óleos Voláteis/química , Antibacterianos/química , Antibacterianos/farmacologia , Brassicaceae/química , Flores/química , Flores/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Hipoglicemiantes/química , Óleos Voláteis/metabolismo , Óleos Voláteis/farmacologia , Folhas de Planta/química , Folhas de Planta/metabolismo , Raízes de Plantas/química , Raízes de Plantas/metabolismo , alfa-Glucosidases/química , alfa-Glucosidases/metabolismo
8.
Food Chem ; 299: 124985, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31279127

RESUMO

Dietary protein peptides from quinoa yoghurt beverage (QYB) fermented with probiotic lactic acid bacteria strains play a protective role against diabetes and hypertension. In this study, the α-glucosidase and ACE inhibitory activities of germination-based protein hydrolysates of QYB were investigated. All protein hydrolysates exhibited a dose and strain-dependent inhibition on the enzymes. The inhibition of α-glucosidase was the highest in QLCSY13 (IC50 = 8.86 mg/mL), while ACE inhibition was the highest in QLCZ (IC50 = 0.03 mg/mL). Overall, QLCSY13 had the highest inhibitory activities, which was ascribed to its relatively higher amino acid contents and hydrophobicity. In addition, the ACE and α-glucosidase inhibitory activities of peptide fractions identified by RP-HPLC were 127 ±â€¯4.29 mg/mL and 10.39 ±â€¯4.73 mg/mL respectively. Among the potent inhibitory peptide sequences identified, both LAHMIVAGA and VAHPVF significantly had α-glucosidase and ACE inhibitory activities. Consequently, dietary protein peptides present in QYB had anti-hypertensive and anti-diabetic potentials.


Assuntos
Bebidas/microbiologia , Lactobacillus casei/metabolismo , Peptidil Dipeptidase A/metabolismo , Hidrolisados de Proteína/farmacologia , Iogurte/microbiologia , alfa-Glucosidases/metabolismo , Sequência de Aminoácidos , Inibidores da Enzima Conversora de Angiotensina/química , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Fermentação , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/farmacologia , Hidrolisados de Proteína/química
9.
Food Chem ; 299: 125102, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31279126

RESUMO

The chemical compositions and α-glucosidase inhibitory activities of anthocyanins extracted from blueberry, blackcurrant and blue honeysuckle fruits and their acid hydrolysates (anthocyanidins) were analysed. Those anthocyanins were glycosidic anthocyanins that converted to anthocyanidins during acid hydrolysis, leading to increases in their α-glucosidase inhibitory activities (expressed as IC50 values) from 0.232, 0.152 and 0.188 to 0.113 to 0.005 and 0.025 mg/mL. The potential inhibitory mechanism of these anthocyanidins was then investigated through inhibition kinetics, fluorescence quenching and docking simulations. The results showed the following: 1) all anthocyanidins were mixed-type inhibitors of α-glucosidase and they bind more tightly to free α-glucosidase as compared to the α-glucosidase-substrate complex; 2) anthocyanidin inhibition of α-glucosidase was a static procedure, presumably driven by hydrophobic associations and hydrogen bonding; and 3) all anthocyanidins were inserted into the active site of α-glucosidase and avoided the entrance of p-nitrophenyl-a-D-glucopyranoside. This study is valuable for anthocyanidins as potential α-glucosidase inhibitors.


Assuntos
Antocianinas/farmacologia , Mirtilos Azuis (Planta)/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Lonicera/química , Ribes/química , Antocianinas/análise , Antocianinas/química , Fluorescência , Frutas/química , Inibidores de Glicosídeo Hidrolases/química , Ligações de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Cinética , Simulação de Acoplamento Molecular , alfa-Glucosidases/química , alfa-Glucosidases/metabolismo
10.
Carbohydr Polym ; 219: 219-228, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31151520

RESUMO

Coreopsis tinctoria is being widely cultivated in Xinjiang of China, whose consumption is known to prevent diabetes and neurodegenerative diseases. To elucidate the bioactive ingredients responsible for these benefits, the alkaline soluble crude polysaccharide (CTB) was isolated from C. tinctoria. In vitro experiments showed that the inhibition of α-amylase and α-glucosidase by CTB was 13407-fold and 906-fold higher than that by positive control, respectively. Then, a novel arabinogalactan, CTBP-1, was isolated and purified from CTB. Structural analysis showed that CTBP-1 possessed a 1,6-linked ß-d-Galp and 1,5-linked α-l-Araf backbone with branches substituted at the C-3 position of the 1,6-linked ß-d-Galp, and the side chains included 1,5-linked α-l-Araf, T-linked ß-d-Galp and T-linked α-l-Araf. The inhibitory effects of CTBP-1 on α-amylase and α-glucosidase were 2.7 and 17.9 times that of acarbose, respectively. CTBP-1 could avoid indigestion and similar side effects. In addition, CTBP-1 remarkably inhibited the release of nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. In summary, CTBP-1 is a novel arabinogalactan with great potential as a treatment for type 2 diabetes and Alzheimer's disease.


Assuntos
Coreopsis/metabolismo , Galactanos , Inibidores de Glicosídeo Hidrolases/farmacologia , Microglia , Extratos Vegetais/química , alfa-Amilases/antagonistas & inibidores , alfa-Glucosidases/metabolismo , Células Cultivadas , China , Galactanos/química , Galactanos/farmacologia , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Microglia/citologia , Microglia/efeitos dos fármacos , Óxido Nítrico/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
11.
Eur J Med Chem ; 177: 362-373, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31158750

RESUMO

Inhibiting the decomposition of carbohydrates into glucose or promoting glucose conversion is considered to be an effective treatment for type 2 diabetes. Herein, a series of novel xanthone-triazole derivatives were designed, synthesized, and their α-glucosidase inhibitory activities and glucose uptake in HepG2 cells were investigated. Most of the compounds showed better inhibitory activities than the parental compound a (1,3-dihydroxyxanthone, IC50 = 160.8 µM) and 1-deoxynojirimycin (positive control, IC50 = 59.5 µM) towards α-glucosidase. Compound 5e was the most potent inhibitor, with IC50 value of 2.06 µM. The kinetics of enzyme inhibition showed that compounds 5e, 5g, 5h, 6c, 6d, 6g and 6h were noncompetitive inhibitors, and molecular docking results were consistent with the noncompetitive property that these compounds bind to allosteric sites away from the active site (Asp214, Glu276 and Asp349). On the other hand, the glucose uptake assays exhibited that compounds 5e, 6a, 6c and 7g displayed high activities in promoting the glucose uptake. The cytotoxicity assays showed that most compounds were low-toxic to human normal hepatocyte cell line (LO2). These novel xanthone triazole derivatives exhibited dual therapeutic effects of α-glucosidase inhibition and glucose uptake promotion, thus they could be use as antidiabetic agents for developing novel drugs against type 2 diabetes.


Assuntos
Glucose/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Hipoglicemiantes/farmacologia , Triazóis/farmacologia , Xantonas/farmacologia , Sítios de Ligação , Desenho de Drogas , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/metabolismo , Inibidores de Glicosídeo Hidrolases/toxicidade , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Humanos , Hipoglicemiantes/síntese química , Hipoglicemiantes/metabolismo , Hipoglicemiantes/toxicidade , Cinética , Simulação de Acoplamento Molecular , Estrutura Molecular , Ligação Proteica , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/metabolismo , Triazóis/toxicidade , Xantonas/síntese química , Xantonas/metabolismo , Xantonas/toxicidade , alfa-Glucosidases/química , alfa-Glucosidases/metabolismo
12.
Food Chem ; 297: 124988, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31253285

RESUMO

Agaricus blazei, Auricularia fuscosuccinea and Pleurotus albidus mycelia were obtained in solid-state cultivation (SSC), using grains (brown rice, canjica corn and wheat) as raw material. Colonized grain flours were analysed for their nutritional, physical and physico-chemical characteristics and biological activity in vitro. Wheat flour with P. albidus showed higher values for protein (18.34 g/100 g), ergosterol (0.60 mg/g), mycelial biomass (183 mg/g) and total amino acids (58.34 mg/g). Corn flour with A. fuscosuccinea showed the highest total phenolic content (2.38 mg GAE/g), antioxidant activity in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) (8.90 µmol TEAC/g) and 2,2'-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) (16.52 µmol TEAC/g) assay. Wheat flour with P. albidus were more effective at inhibiting of pancreatic lipase (74.5%) and of α-glucosidase (98.2%). In conclusion, grains colonized by macrofungi mycelia through SSC can enrich the nutritional value and the biological activity of the flours, which presents a potential for functional foods.


Assuntos
Agaricus/fisiologia , Farinha/análise , Valor Nutritivo , Pleurotus/fisiologia , Aminoácidos/química , Antioxidantes/química , Biomassa , Ergosterol/análise , Lipase/antagonistas & inibidores , Lipase/metabolismo , Oryza/metabolismo , Fenóis/análise , Triticum/metabolismo , Zea mays/metabolismo , alfa-Glucosidases/química , alfa-Glucosidases/metabolismo
13.
Talanta ; 200: 279-287, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31036185

RESUMO

Plants are well-recognized sources of inhibitors for α-glucosidase - a key target enzyme for management of type 2 diabetes. Recently, two advanced bioactivity-profiling techniques, i.e., ligand fishing and high-resolution inhibition profiling, have shown great promises for accelerating identification of α-glucosidase inhibitors from complex plant extracts. Non-specific affinities and non-specific inhibitions are major sources of false positive hits from ligand fishing and high-resolution inhibition profiling, respectively. In an attempt to minimize such false positive hits, we describe a new screening approach based on ligand fishing and high-resolution inhibition profiling for detection of high-affinity ligands and assessment of inhibitory activity, respectively. The complementary nature of ligand fishing and high-resolution inhibition profiling was explored to identify α-glucosidase inhibitory ligands from a complex mixture, and proof-of-concept was demonstrated with crude ethyl acetate extract of Ginkgo biloba. In addition to magnetic beads with a 3-carbon aliphatic linker, α-glucosidase was immobilized on magnetic beads with a 21-carbon aliphatic linker; and the two different types of magnetic beads were compared for their hydrolytic activity and fishing efficiency.


Assuntos
Biflavonoides/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Extratos Vegetais/farmacologia , alfa-Glucosidases/metabolismo , Biflavonoides/química , Biflavonoides/isolamento & purificação , Avaliação Pré-Clínica de Medicamentos , Ginkgo biloba/química , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Ligantes , Fenômenos Magnéticos , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Saccharomyces cerevisiae/enzimologia , Relação Estrutura-Atividade
14.
J Enzyme Inhib Med Chem ; 34(1): 937-945, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31072245

RESUMO

In this article, 23 compounds (6 and 7a-7v) were prepared and evaluated for their in vitro α-glucosidase inhibitory activity. The compounds 7d, 7f, 7i, 7n, 7o, 7r, 7s, 7u, and 7v displayed the α-glucosidase inhibition activity with IC50 values ranging from 1.68 to 7.88 µM. Among all tested compounds, 7u was found to be the most efficient, being 32-fold more active than the standard drug acarbose, which significantly attenuated postprandial blood glucose in mice. In addition, the compound 7u also induced the fluorescence quenching and conformational changes of enzyme, by forming α-glucosidase-7u complex in a mixed inhibition type. The thermodynamic constants recognised the interaction between 7u and α-glucosidase and was an enthalpy-driven spontaneous exothermic reaction. The synchronous fluorescence and CD spectra also indicate that the compound 7u changed the enzyme conformation. The findings identify the binding interactions between new ligands and α-glucosidase and reveal the compound 7u as a potent α-glucosidase inhibitor.


Assuntos
Acetofenonas/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , alfa-Glucosidases/metabolismo , Acetofenonas/síntese química , Acetofenonas/química , Relação Dose-Resposta a Droga , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/química , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Termodinâmica
15.
Phytochemistry ; 164: 60-66, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31096077

RESUMO

Fifteen phenylpropanoid glycosides, including six undescribed compounds were isolated from the fruit of Lycium barbarum L. (Solanaceae) (goji or wolfberry). Their structures were identified by detailed spectroscopic analyses. Seven known compounds were firstly isolated from the genus Lycium, in which the 1D and 2D NMR data of one compound were reported for the first time. Notably, two undescribed compounds were a pair of rare tautomeric glycoside anomers characterized by the presence of free anomeric hydroxy. Antioxidant and hypoglycemic activities of all these compounds were assessed using DPPH radical scavenging, oxygen radical absorbance capacity (ORAC), and α-glucosidase inhibitory assays, respectively. These compounds showed different levels of oxygen radical absorbance capacity, and some isolates exhibited potent antioxidant activity with greater ORAC values than the positive control (EGCG).


Assuntos
Antioxidantes/farmacologia , Frutas/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Glicosídeos/farmacologia , Lycium/química , Fenilpropionatos/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Compostos de Bifenilo/antagonistas & inibidores , Relação Dose-Resposta a Droga , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Glicosídeos/química , Glicosídeos/isolamento & purificação , Conformação Molecular , Fenilpropionatos/química , Fenilpropionatos/isolamento & purificação , Picratos/antagonistas & inibidores , Espécies Reativas de Oxigênio/antagonistas & inibidores , Relação Estrutura-Atividade , alfa-Glucosidases/metabolismo
16.
Microb Pathog ; 132: 222-229, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31059755

RESUMO

The emerging incidence of antibiotic resistance trait among the bacteria populating poultry presents a devastating public health issue. On the other hand, at present, diabetes and obesity are the most serious public health issues and are increasing subsequently at alarming rate. In view of this, the present in vitro context was aimed to investigate the antibacterial activities of Momordica charantia (M. charantia) fruits extracts against poultry associated Bacillus spp. and to assess further its phytoconstituents, alpha-(α)-glucosidase activities, and anti-obesity properties. The anti-pathogenic attributes of M. charantia fruit extracts were carried out using disc diffusion assay and results showed the pronounced antibacterial trait of ethanolic extract with maximum zone of inhibition of 28.3 ±â€¯1.2 mm against Bacillus licheniformis. The qualitative phytochemical analyses of fruit extracts illustrated the presence of diverse phytoconstituents. The α-glucosidase inhibition assay for the extracts was performed according to the α-glucosidase activity kit. The results depicted the lowest α-glucosidase activity (57.13 ±â€¯2.3 to 18.14 ±â€¯1.3 U/L) in the presence of ethanolic extract at varied concentrations. The anti-obesity potentialities of fruit extracts were demonstrated in terms of porcine pancreatic lipase (PPL type II) activity using p-nitro-phenyl butyrate (p-NPB) as a substrate. The ethanolic extract of M. charantia fruits was observed to exhibit maximum inhibition of pancreatic lipase ranging from 20.12 ±â€¯2.3 to 68.34 ±â€¯1.3% in a dose dependent manner with an IC50 value of 607.6 ±â€¯1.3 µg/mL. FTIR and GC-MS results indicated the presence of distinct compounds in the ethanol extract and major bioactive constituents were found to be Dimethyl sulfone (35.24%), 9-octadecanamide (20.52%), Pentadecanoic acid (6.64%), Lanost-9 (11)-en-18-oic acid, 23-(acetylxyl)-3-(4-bromobenzoyl) oxyl-20-hydroxyl-gamma-lactone (2.6%), and 2,2-sulfonyldiethanol (2.46%). In conclusion, M. charantia fruits could be of great concern in pharmaceutical industries due to its adequate biological properties and may also help in the management of poultry associated bacterial pathogens.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Frutas/química , Momordica charantia/química , Extratos Vegetais/farmacologia , Animais , Fármacos Antiobesidade/farmacologia , Bacillus/efeitos dos fármacos , Lipase/metabolismo , Testes de Sensibilidade Microbiana , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Aves Domésticas , Doenças das Aves Domésticas/tratamento farmacológico , Doenças das Aves Domésticas/microbiologia , Suínos , alfa-Glucosidases/metabolismo
17.
Molecules ; 24(9)2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31071910

RESUMO

α-glucosidase inhibitors (AGIs) have been an important category of oral antidiabetic drugs being widely exploited for the effective management of type 2 diabetes mellitus. However, the marketed AGIs not only inhibited the disaccharidases, but also exhibited an excessive inhibitory effect on α-amylase, resulting in undesirable gastrointestinal side effects. Compared to these agents, Ramulus Mori alkaloids (SZ-A), was a group of effective alkaloids from natural Morus alba L., and showed excellent hypoglycemic effect and fewer side effects in the Phase II/III clinical trials. Thus, this paper aims to investigate the selective inhibitory effect and mechanism of SZ-A and its major active ingredients (1-DNJ, FA and DAB) on different α-glucosidases (α-amylase and disaccharidases) by using a combination of kinetic analysis and molecular docking approaches. From the results, SZ-A displayed a strong inhibitory effect on maltase and sucrase with an IC50 of 0.06 µg/mL and 0.03 µg/mL, respectively, which was similar to the positive control of acarbose with an IC50 of 0.07 µg/mL and 0.68 µg/mL. With regard to α-amylase, SZ-A exhibited no inhibitory activity at 100 µg/mL, while acarbose showed an obvious inhibitory effect with an IC50 of 1.74 µg/mL. The above analysis demonstrated that SZ-A could selectively inhibit disaccharidase to reduce hyperglycemia with a reversible competitive inhibition, which was primarily attributed to the three major active ingredients of SZ-A, especially 1-DNJ molecule. In the light of these findings, molecular docking study was utilized to analyze their inhibition mechanisms at molecular level. It pointed out that acarbose with a four-ring structure could perform desirable interactions with various α-glucosidases, while the three active ingredients of SZ-A, belonging to monocyclic compounds, had a high affinity to the active site of disaccharidases through forming a wide range of hydrogen bonds, whose affinity and consensus score with α-amylase was significantly lower than that of acarbose. Our study illustrates the selective inhibition mechanism of SZ-A on α-glucosidase for the first time, which is of great importance for the treatment of type 2 diabetes mellitus.


Assuntos
Alcaloides/metabolismo , Simulação de Acoplamento Molecular , Morus/química , alfa-Glucosidases/metabolismo , Alcaloides/química , Animais , Domínio Catalítico , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Cinética , Ligantes , Ratos Wistar , Solventes , Sacarase/metabolismo
18.
Food Chem Toxicol ; 130: 207-218, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31128218

RESUMO

α-glucosidase inhibition is a rational approach in the effective management of type 2 diabetes. Several inhibitors of this enzyme class are in clinical use, but are riddled with efficacy, potency and safety challenges. For this reason, new effective α-glucosidase inhibitors are under investigation. Compounds with 1, 3, 4-oxadiazole nucleus have shown preclinical efficacy as α-glucosidase inhibitors and as anti-inflammatory agents. Moreover, 1, 3, 4-oxadiazoles also play important role in pesticide chemistry, polymer science, and they are considered as the building blocks in the production of new molecular agents for bioactive molecules. In the present study, computational analyses were carried out for various 1,3,4-oxadiazole (which were divided into BF2 & BF3 series); the most active compound was taken as a potent inhibitor, and pharmacophore were formed from that compound, followed by validation against a test database. The pharmacophore-based virtual screening was performed and, by successive eliminations, six compounds of different interactions with the significant amino acid residues were selected as the lead compounds. It is concluded that these six compounds with 1, 3, 4-oxadiazoles nucleus might be used as promising drug candidates in α-glucosidase inactivation and thus we recommend further in vitro and in vivo pharmacological and safety studies.


Assuntos
Oxidiazóis/química , Oxidiazóis/farmacologia , alfa-Glucosidases/metabolismo , Descoberta de Drogas , Inibidores de Glicosídeo Hidrolases/farmacologia , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , alfa-Glucosidases/genética
19.
Eur J Med Chem ; 176: 343-377, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31112894

RESUMO

α-Glucosidase enzyme inhibition is an effective therapeutic decorum in the treatment of type 2 diabetes mellitus. Since 1990, three α-glucosidase inhibitors are known to exist clinically, Acarbose, Voglibose and Miglitol. Side effects and long synthetic routes to access them forced the researchers to move their focus to discover simple and small heterocyclic motifs that work as promising α-glucosidase inhibitors and may eventually lead to the management of postprandial hyperglycemic condition in T2DM. In this regards, this review deals with recently discovered heterocyclic molecules that have been evaluated to exhibit inhibition of α-glucosidase enzyme.


Assuntos
Inibidores de Glicosídeo Hidrolases/química , Compostos Heterocíclicos/química , Animais , Linhagem Celular Tumoral , Inibidores de Glicosídeo Hidrolases/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/toxicidade , Compostos Heterocíclicos/metabolismo , Compostos Heterocíclicos/farmacologia , Compostos Heterocíclicos/toxicidade , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/metabolismo , Hipoglicemiantes/farmacologia , Hipoglicemiantes/toxicidade , Simulação de Acoplamento Molecular , Estrutura Molecular , Ligação Proteica , Relação Estrutura-Atividade , alfa-Glucosidases/química , alfa-Glucosidases/metabolismo
20.
Mar Drugs ; 17(5)2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31121891

RESUMO

Hizikia fusiformis (Harvey) Okamura is an edible marine alga that has been widely used in Korea, China, and Japan as a rich source of dietary fiber and essential minerals. In our previous study, we observed that the methanol extract of H. fusiformis and its non-polar fractions showed potent protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase inhibition. Therefore, the aim of the present study was to identify the active ingredient in the methanol extract of H. fusiformis. We isolated a new glycerol fatty acid (13) and 20 known compounds including 9 fatty acids (1-3, 7-12), mixture of 24R and 24S-saringosterol (4), fucosterol (5), mixture of 24R,28R and 24S,28R-epoxy-24-ethylcholesterol (6), cedrusin (14), 1-(4-hydroxy-3-methoxyphenyl)-2-[2-hydroxy -4-(3-hydroxypropyl)phenoxy]-1,3-propanediol (15), benzyl alcohol alloside (16), madhusic acid A (17), glycyrrhizin (18), glycyrrhizin-6'-methyl ester (19), apo-9'-fucoxanthinone (20) and tyramine (21) from the non-polar fraction of H. fusiformis. New glycerol fatty acid 13 was identified as 2-(7'- (2″-hydroxy-3″-((5Z,8Z,11Z)-icosatrienoyloxy)propoxy)-7'-oxoheptanoyl)oxymethylpropenoic acid by spectroscopic analysis using NMR, IR, and HR-ESI-MS. We investigated the effect of the 21 isolated compounds and metabolites (22 and 23) of 18 against the inhibition of PTP1B and α-glucosidase enzymes. All fatty acids showed potent PTP1B inhibition at low concentrations. In particular, new compound 13 and fucosterol epoxide (6) showed noncompetitive inhibitory activity against PTP1B. Metabolites of glycyrrhizin, 22 and 23, exhibited competitive inhibition against PTP1B. These findings suggest that H. fusiformis, a widely consumed seafood, may be effective as a dietary supplement for the management of diabetes through the inhibition of PTP1B.


Assuntos
Extratos Vegetais/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Sargassum/química , alfa-Glucosidases/metabolismo , Suplementos Nutricionais , Ativação Enzimática/efeitos dos fármacos , Ácidos Graxos/química , Ácidos Graxos/isolamento & purificação , Ácidos Graxos/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Metanol/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação
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