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1.
J Chromatogr A ; 1642: 462041, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33721816

RESUMO

Cortex Lycii, as a kind of traditional Chinese medicines, have shown prospects in the prevention of diabetes and its complications. However, there is comparatively little information regarding the characterization of potentially hypoglycemic compounds derived from Cortex Lycii. In this study, we performed a global non-selective investigation of α-glucosidase inhibitors in Cortex Lycii based on a bioactivity-labeling high-resolution mass spectrometry-metabolomics method. Samples of Cortex Lycii were collected from different Chinese provinces and their ethyl acetate extracts were analyzed using an in vitro α-glucosidase inhibition assay for bioactivity-labeling. The ethyl acetate extracts were also subjected to liquid chromatography-mass spectrometry analysis and multivariate data analysis was subsequently conducted to identify correlations between the bioactivity measured from the enzyme-involved test and the profiles obtained based on high-resolution mass spectrometry. The variables contributing significantly to the separation of the more-active from the less-active samples were considered to indicate the potential target ions of active compounds. MS/MS fragment patterns and nuclear magnetic resonance analyses were used to identify the potential target ions. The developed platform mentioned above facilitated rapid identification of four α-glucosidase inhibitors, namely, N-p-trans-coumaroyltyramine (1), N-trans-caffeoyl-tyramine (2), (9R,10E,12Z)-9-hydroxy-10,12-octadecadienoic acid (3a), and (9S,10E,12Z)-9-hydroxy-10,12-octadecadienoic acid (3b) from Cortex Lycii. The α-glucosidase inhibitory activities of compounds 3a and 3b with IC50 values of 1.0413±0.0551 and 1.0423±0.0049 mM, respectively, are reported here for the first time. Enzyme kinetics revealed that both 3a and 3b were non-competitive inhibitors of α-glucosidase, with Ki values of 2.20 and 2.24 mM, respectively. In short, the presented work identified compounds 3a and 3b as potential α-glucosidase inhibitors with higher inhibitory activity and a different mode of inhibition compared to the standard α-glucosidase inhibitor, acarbose. The integrated approach adopted in this study can be extended as a normalized procedure to rapidly identify active compounds, even from complex extracts, and can readily be adapted for the study of other natural products.


Assuntos
Medicamentos de Ervas Chinesas/química , Inibidores de Glicosídeo Hidrolases/análise , Espectrometria de Massas , Metabolômica , Cromatografia Líquida de Alta Pressão , Inibidores de Glicosídeo Hidrolases/química , Concentração Inibidora 50 , Íons , Cinética , Espectroscopia de Ressonância Magnética , Análise Multivariada , Extratos Vegetais/química , Análise de Componente Principal , Reprodutibilidade dos Testes , alfa-Glucosidases/metabolismo
2.
Molecules ; 26(4)2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33672038

RESUMO

Our previous study found that desmethylxanthohumol (1) inhibited α-glucosidase in vitro. Recently, further investigations revealed that dehydrocyclodesmethylxanthohumol (2) and its dimer analogue rottlerone (3) exhibited more potent α-glucosidase inhibitory activity than 1. The aim of this study was to synthesize a series of rottlerone analogues and evaluate their α-glucosidase and DPP-4 dual inhibitory activity. The results showed that compounds 4d and 5d irreversibly and potently inhibited α-glucosidase (IC50 = 0.22 and 0.12 µM) and moderately inhibited DPP-4 (IC50 = 23.59 and 26.19 µM), respectively. In addition, compounds 4d and 5d significantly promoted glucose consumption, with the activity of 5d at 0.2 µM being comparable to that of metformin at a concentration of 1 mM.


Assuntos
Inibidores da Dipeptidil Peptidase IV/farmacologia , Flavonoides/síntese química , Flavonoides/farmacologia , Glucose/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Propiofenonas/síntese química , Propiofenonas/farmacologia , Dipeptidil Peptidase 4/metabolismo , Flavonoides/química , Células Hep G2 , Humanos , Cinética , Propiofenonas/química , alfa-Glucosidases/metabolismo
3.
Eur J Med Chem ; 216: 113322, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33652353

RESUMO

In this paper, the 2,5-disubstituted furan derivatives containing 1,3,4-thiadiazole were synthesized and screened for their inhibitory activity against α-glucosidase and ß-glucuronidases to obtain potent α-glucosidase inhibitor 9 (IC50 = 0.186 µM) and E. coli ß-glucuronidase inhibitor 26 (IC50 = 0.082 µM), respectively. The mechanisms of the compounds were studied. The kinetic study revealed that compound 9 is a competitive inhibitor against α-glucosidase (Ki = 0.05 ± 0.003 µM) and molecular docking simulation showed several key interactions between 9 and the target including hydrogen bond and p-π stacking interaction. Derivative 26 (Ki = 0.06 ± 0.005 µM) displayed uncompetitive inhibition behavior against EcGUS. Furthermore, the result of docking revealed the furan ring of 26 may be a key moiety in obstructing the active domain of EcGUS. In addition, compound 15 exhibited significant inhibitory activity against these two enzymes, with potential therapeutic effects against diabetes and against CPT-11-induced diarrhea. At the same time, their low toxicity against normal liver tissue LO2 cells lays the foundation for in vivo studies and the development of bifunctional drug.


Assuntos
Escherichia coli/enzimologia , Furanos/química , Glicoproteínas/química , Inibidores de Glicosídeo Hidrolases/química , Tiadiazóis/química , Sítios de Ligação , Domínio Catalítico , Linhagem Celular , Sobrevivência Celular , Proteínas de Escherichia coli/antagonistas & inibidores , Proteínas de Escherichia coli/metabolismo , Furanos/farmacologia , Glucuronidase/antagonistas & inibidores , Glucuronidase/metabolismo , Glicoproteínas/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Cinética , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade
4.
Food Chem ; 350: 129241, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33601092

RESUMO

The Araucaria araucana kernels are a traditional food in southern Chile and Argentina. The aim of this work was to determine the composition of the phenolic-enriched extracts (PEEs) of the boiled kernels as well as their antioxidant capacity, inhibitory activity on metabolic syndrome-associated enzymes and effect on postprandial oxidative stress in a simulated gastric digestion model. The PEEs composition was assessed by HPLC-DAD-MS/MS. The main PEEs constituents were catechin and epicatechin in the unbound form, while hydroxybenzoic acids occurred mainly in the bound form. The unbound phenolics from boiled kernels showed significant correlations with DPPH, FRAP, TEAC (Pearson's r of 0.481, 0.331 and 0.417, respectively) and lipid peroxidation (r = 0.381) and were more active than the bound phenolics. The extracts were highly active against α-glucosidase (IC50: 0.33-3.15 µg/mL) and reduced lipoperoxidation. Traditional processing increases the flavan-3-ol content. Our results suggest that this traditional food has potential health promoting properties.


Assuntos
Antioxidantes/farmacologia , Araucaria araucana/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Antioxidantes/química , Chile , Flavonoides/análise , Estresse Oxidativo , Espectrometria de Massas em Tandem
5.
Molecules ; 26(3)2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33573121

RESUMO

Metabolic syndrome (MetS) is a global public health problem affecting nearly 25.9% of the world population characterised by a cluster of disorders dominated by abdominal obesity, high blood pressure, high fasting plasma glucose, hypertriacylglycerolaemia and low HDL-cholesterol. In recent years, marine organisms, especially seaweeds, have been highlighted as potential natural sources of bioactive compounds and useful metabolites, with many biological and physiological activities to be used in functional foods or in human nutraceuticals for the management of MetS and related disorders. Of the three groups of seaweeds, brown seaweeds are known to contain more bioactive components than either red and green seaweeds. Among the different brown seaweed species, Ascophyllum nodosum and Fucus vesiculosus have the highest antioxidant values and highest total phenolic content. However, the evidence base relies mainly on cell line and small animal models, with few studies to date involving humans. This review intends to provide an overview of the potential of brown seaweed extracts Ascophyllum nodosum and Fucus vesiculosus for the management and prevention of MetS and related conditions, based on the available evidence obtained from clinical trials.


Assuntos
Ascophyllum/química , Fucus/química , Síndrome Metabólica/dietoterapia , Extratos Vegetais/uso terapêutico , Ensaios Clínicos como Assunto , Inibidores de Glicosídeo Hidrolases/uso terapêutico , Humanos , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/patologia , Extratos Vegetais/química , Alga Marinha/química
6.
J Environ Sci Health B ; 56(3): 282-291, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33397190

RESUMO

In the present study, α-amylase and α-glucosidase inhibitory effect and antioxidant activity of capsaicin and piperine from the ethanolic extract of Capsicum chinense (EECch) and Piper nigrum (EEPn) fruits were investigated. Results revealed that EECch exhibited the highest phenolic (154 mg GAE/100 g of tissue) and flavonoid content (75 mg RtE/100 g of tissue) in comparison with EEPn. The predominant compound detected in EECch and EEPn by GC-EIMS analysis was the capsaicin and piperine, respectively. The capsaicin and piperine showed the highest α-amylase and α-glucosidase inhibitory effect and antioxidant activity rather than extracts. The EEPn (IC50= 216 µg/mL) and piperine (IC50= 105 µg/mL) present a highest α-amylase inhibitory effect, while the EECch (IC50= 225 µg/mL) and capsaicin (IC50= 117 µg/mL) showed highest anti-α-glucosidase activity. Molecular docking established that capsaicin and piperine bind at the α-glucosidase and α-amylase through hydrophobic interactions, hydrogen bond, and charge interactions with amino acid residues. The enzyme inhibitory activity and antioxidant properties exhibited by EECch and EEPn could be attributed to the capsaicin and piperine content and other compounds present such as phenolic compounds and flavonoids. These fruits are potential sources of natural antioxidant agents and α-amylase and α-glucosidase inhibitors.


Assuntos
Alcaloides/farmacologia , Benzodioxóis/farmacologia , Capsaicina/farmacologia , Capsicum/química , Inibidores Enzimáticos/farmacologia , Piper nigrum/química , Piperidinas/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , alfa-Amilases/antagonistas & inibidores , Frutas/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Extratos Vegetais/química
7.
Molecules ; 26(2)2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33466863

RESUMO

Four new phenanthrene derivatives, gastrobellinols A-D (1-4), were isolated from the methanolic extract of Gastrochilus bellinus (Rchb.f.) Kuntze, along with eleven known phenolic compounds including agrostophyllin (5), agrostophyllidin (6), coniferyl aldehyde (7), 4-hydroxybenzaldehyde (8), agrostophyllone (9), gigantol (10), 4-(methoxylmethyl)phenol (11), syringaldehyde (12), 1-(4'-hydroxybenzyl)-imbricartin (13), 6-methoxycoelonin (14), and imbricatin (15). Their structures were determined by spectroscopic methods. Each isolate was evaluated for α-glucosidase inhibitory activity. Compounds 1, 2, 3, 7, 9, 13, and 15 showed higher activity than the drug acarbose. Gastrobellinol C (3) exhibited the strongest α-glucosidase inhibition with an IC50 value of 45.92 µM. A kinetic study of 3 showed competitive inhibition on the α-glucosidase enzyme. This is the first report on the phytochemical constituents and α-glucosidase inhibitory activity of G. bellinus.


Assuntos
Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Orchidaceae/química , Fenantrenos/química , Extratos Vegetais/farmacologia , alfa-Glucosidases/química
8.
Food Chem ; 347: 129056, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33476922

RESUMO

Flavonoid compounds have anti-diabetic activity, which can control blood glucose levels by inhibiting α-glucosidase activity. In this paper, the inhibition mechanisms between four flavonoid compounds and α-glucosidase were studied by multispectroscopic methods and molecular docking. The results showed that the inhibitory activities of flavonoid compounds were higher than that of acarbose, and the sequence of inhibition effect was scutellarein > nepetin > apigenin > hispidulin > acarbose. Also, the synergistic effects of flavonoid compounds combined with acarbose on inhibiting α-glucosidase activity were observed. The fluorescence results showed that flavonoid compounds combined with α-glucosidase to form a stable complex. And the spectral analysis indicated that the microenvironmental and secondary structure of α-glucosidase were changed. The present study demonstrated that the molecular structure of flavonoid compounds played an important role in the inhibition process, namely, scutellarein with more hydroxyl groups on the A-ring might serve as the most effective α-glucosidase inhibitor.


Assuntos
Acarbose/química , Flavonoides/química , Inibidores de Glicosídeo Hidrolases/química , alfa-Glucosidases/química , Acarbose/metabolismo , Apigenina/química , Apigenina/metabolismo , Sítios de Ligação , Diabetes Mellitus/tratamento farmacológico , Sinergismo Farmacológico , Flavonas/química , Flavonas/metabolismo , Flavonoides/metabolismo , Flavonoides/uso terapêutico , Inibidores de Glicosídeo Hidrolases/metabolismo , Inibidores de Glicosídeo Hidrolases/uso terapêutico , Humanos , Cinética , Simulação de Acoplamento Molecular , Termodinâmica , alfa-Glucosidases/metabolismo
9.
Life Sci ; 274: 119069, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33460667

RESUMO

As a complicated metabolic disorder, type 2 diabetes mellitus (T2DM) is becoming a major health concern worldwide. Drugs including acarbose, saxagliptin and vildagliptin are applied, but their efficacy is still required to be compared. Therefore, the study aimed to evaluate the efficacy and safety of acarbose, saxagliptin and vildagliptin in the treatment of T2DM. Ninety patients diagnosed with T2DM were treated with acarbose, saxagliptin and vildagliptin, respectively (30 patients for each drug). All patients were examined at 0, 4 and 12 weeks after treatment with vital signs recorded. Fasting blood glucose and blood biochemical indices were analyzed. In addition, fecal samples were taken for microbial macrogenome sequencing and safety evaluation within 12 weeks after treatment. Blood glucose level decreased at 4 and 12 weeks after treatment, and the total cholesterol (TC) and high-density lipoprotein (HDL) levels at 12 weeks were different. Genus abundance of intestinal flora was altered at different time points. Acarbose increased Butyricimonas level first and then decreased it during drug treatment. Saxagliptin increased Megamonas and decreased Turicibacter genus level gradually. Pseudomonas, Klebsiella, Blautia, Faecalibacterium and Roseburia levels fluctuated after Vildagliptin treatment, which increased fasting C-peptide level greater than the other two drugs. Saxagliptin showed higher adverse reactions than acarbose and vildagliptin. Collectively, acarbose, vildagliptin, and saxagliptin can effectively reduce the HbA1c level and affect the intestinal flora distribution in T2DM patients, and the adverse reactions of acarbose and vildagliptin are less than saxagliptin, providing alternative strategies for the treatment of T2DM.


Assuntos
Acarbose/uso terapêutico , Adamantano/análogos & derivados , Biomarcadores/análise , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dipeptídeos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Vildagliptina/uso terapêutico , Adamantano/uso terapêutico , Glicemia/análise , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Feminino , Seguimentos , Hemoglobina A Glicada/análise , Inibidores de Glicosídeo Hidrolases/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
10.
Int J Biol Macromol ; 172: 503-514, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33454330

RESUMO

The study aimed to reveal the different mechanisms of delaying starch digestion by ECG, EGCG and Procyanidin based on the perspective of α-amylase-flavanol interaction and starch-flavanol interaction. The interaction characteristics of flavanols with α-amylase were studied from five aspects: enzyme inhibition, kinetics, fluorescence quenching, circular dichroism (CD) and computer simulation. The IC50 of flavanols (ECG, EGCG and Procyanidin) against α-amylase were 172.21 ± 0.22, 732.15 ± 0.13 and 504.45 ± 0.19 µg/mL according to the results of α-amylase inhibition experiment, respectively. ECG and Procyanidin showed mixed inhibition against α-amylase, while EGCG showed non-competition against α-amylase. However, thermodynamic parameters,computer-based docking and dynamic simulation proved that ECG and EGCG-α-amylase complexs were mainly driven by van der Waals and hydrogen bonds, while Procyanidin-α-amylase complexs was driven by hydrophobic interaction. In addition, it was indicated, by means of starch­iodine complex spectroscopy, that flavanols inhibited the digestion of starch not only through bind with α-amylase but also through bind with starch. Thus, flavanols as a starch-based food additive have the potential to be employed as adjuvant therapy for diabetes.


Assuntos
Biflavonoides/química , Catequina/análogos & derivados , Inibidores de Glicosídeo Hidrolases/química , Proantocianidinas/química , Amido/química , alfa-Amilases/química , Biflavonoides/metabolismo , Sítios de Ligação , Catequina/química , Catequina/metabolismo , Glucose/química , Inibidores de Glicosídeo Hidrolases/metabolismo , Hidrólise , Cinética , Maltose/química , Maltose/metabolismo , Simulação de Acoplamento Molecular , Proantocianidinas/metabolismo , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Amido/metabolismo , Especificidade por Substrato , Termodinâmica , Trissacarídeos/química , Trissacarídeos/metabolismo , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/metabolismo
11.
Molecules ; 26(2)2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33430115

RESUMO

Withania frutescens L. is a wild perennial woody plant used by the local population for diverse therapeutic purposes. This work aims to study for the first time the potential inhibitory effect of this plant hydroethanolic extract on α-amylase and α-glucosidase activities using in vitro methods and its antidiabetic and antihyperglycemic activities using alloxan-induced diabetic mice as a model for experimental diabetes. Two doses were selected for the in vivo study (200 and 400 mg/kg) and glibenclamide, a well-known antidiabetic drug (positive control) in a subacute study (28 days) where the antihyperglycemic activity was also assessed over a period of 12 h on diabetic mice. The continuous treatment of diabetic mice with the extract of Withania frutescens for 4 weeks succeeded to slowly manage their high fasting blood glucose levels (after two weeks), while the antihyperglycemic test result revealed that the extract of this plant did not control hyperglycemia in the short term. No toxicity signs or death were noted for the groups treated with the plant extract, and it shows a protective effect on the liver and kidney. The in vitro assays demonstrated that the inhibition of alpha-amylase and alpha-glucosidase might be one of the mechanisms of action exhibited by the extract of this plant to control and prevent postprandial hyperglycemia. This work indicates that W. frutescens have an important long term antidiabetic effect that can be well established to treat diabetes.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Inibidores de Glicosídeo Hidrolases , Hipoglicemiantes , Extratos Vegetais , Folhas de Planta/química , Withania/química , alfa-Amilases/antagonistas & inibidores , Animais , Diabetes Mellitus Experimental/enzimologia , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Camundongos , Extratos Vegetais/química , Extratos Vegetais/farmacologia
12.
Yakugaku Zasshi ; 141(1): 15-24, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-33390442

RESUMO

Iminosugars are one of the compounds that mimic the structure of monosaccharides. Such sugar mimics have the ability to effectively and specifically inhibit various glycosidases and glycosyltransferases. After studying iminopyranose, miglitol, which has α-glucosidase inhibitory activity, was approved and used in the clinical treatment of diabetes. This study focused on l-iminofuranose derivatives to develop new anti-diabetic drug. As a result, it was found that l-iminofuranose having an alkyl group at C1 position show potent α-glucosidase inhibitory activity. Further structural-activity relationship studies were conducted, and interesting findings were obtained. This paper describes the details of those research developments.


Assuntos
1-Desoxinojirimicina/análogos & derivados , Diabetes Mellitus/tratamento farmacológico , Inibidores de Glicosídeo Hidrolases , Hipoglicemiantes , Imino Piranoses/síntese química , Imino Piranoses/farmacologia , 1-Desoxinojirimicina/síntese química , 1-Desoxinojirimicina/química , 1-Desoxinojirimicina/farmacologia , 1-Desoxinojirimicina/uso terapêutico , Animais , Humanos , Imino Piranoses/química , Imino Piranoses/uso terapêutico , Relação Estrutura-Atividade , alfa-Glucosidases
13.
Food Chem ; 346: 128606, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33388667

RESUMO

The impact of extrusion at different barrel temperature and screw speed on the hempseed hull was investigated. The extrusion treatments showed significant (p < 0.05) increase in total phenolic content, proportion of free phenolic compounds, and DPPH and ABTS radical scavenging activities. At low screw speed (150 rpm), significantly (p < 0.05) higher α-glucosidase and acetylcholinesterase inhibition activities were observed in the extruded samples. The full factorial model revealed a significant interaction between extrusion parameters on total phenolic/flavonoid content and antioxidant activities for free fraction, and α-glucosidase and acetylcholinesterase inhibition for whole fraction. A total of 26 phenylpropionamides, including hydroxycinnamic acid amides and lignanamides, were identified by HPLC-ESI-QTOF-MS/MS. HPLC-DAD analysis showed a 25-78% increase in total phenylpropionamide content in hempseed hull after extrusion. Pearson's correlation displayed significant (p < 0.05) positive correlation of N-trans-caffeoyltyramine, the most abundant phenylpropionamide, with all biological activities (r = 0.832-0.940).


Assuntos
Antioxidantes/química , Cannabis/química , Fenóis/química , Inibidores da Colinesterase/farmacologia , Cromatografia Líquida de Alta Pressão , Flavonoides/análise , Inibidores de Glicosídeo Hidrolases/farmacologia , Extratos Vegetais/química , Espectrometria de Massas em Tandem
14.
Fitoterapia ; 149: 104823, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33387642

RESUMO

Four new cyclohexene derivatives cladoscyclitols A-D (1-4) and one new ribofuranose phenol derivative 4-O-α-D-ribofuranose-2-pentyl-3-phemethylol (5) were obtained from the EtOAC extract of the mangrove-derived endophytic fungus Cladosporium sp. JJM22. The structures were elucidated by extensive NMR and MS analysis, while the absolute configurations of the stereogenic carbons were established based on quantum-chemical electronic circular dichroism calculations or comparison of the optical rotations with those of related compounds. Compounds 2 and 5 displayed potent inhibitory activity against α-glucosidase with the IC50 values of 2.95 and 2.05 µM, respectively.


Assuntos
Cladosporium/química , Cicloexenos/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Rhizophoraceae/microbiologia , China , Cicloexenos/isolamento & purificação , Endófitos/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Testes de Sensibilidade Microbiana , Estrutura Molecular
15.
Carbohydr Polym ; 253: 117190, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33278967

RESUMO

In this study, two polysaccharide components named WSRP-2a and WSRP-2b, were purified from Rosa setate x Rosa rugosa waste via anion exchange and gel filtration chromatography. Monosaccharide composition, Congo red assay, FT-IR and NMR spectra analysis confirmed that both of these fractions were mainly composed of galacturonic acid, arabinose, galactose and rhamnose, which were pectin-type polysaccharides with non-triple-helix structure. WSRP-2a and WSRP-2b, however, differed in molecular weight of 56.8 kD and 23.9 kD. The followed bioassay presented their impressive hypoglycemic and immunomodulatory activities. WSRP-2a promoted more proliferation, NO release, and the secretion of cytokines in RAW264.7 macrophages, while WSRP-2b presented higher α-amylase and α-glucosidase inhibitory activities. Collectively, these results suggested that the Rosa Setate x Rosa Rugosa waste biomass could be used as a promising source of bioactive pectic polysaccharides.


Assuntos
Hipoglicemiantes/química , Fatores Imunológicos/química , Pectinas/química , Extratos Vegetais/química , Rosa/química , Animais , Arabinose , Citocinas/metabolismo , Galactose , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/farmacologia , Ácidos Hexurônicos , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia , Fatores Imunológicos/isolamento & purificação , Fatores Imunológicos/farmacologia , Macrófagos/imunologia , Camundongos , Peso Molecular , Pectinas/isolamento & purificação , Pectinas/farmacologia , Fagocitose/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Células RAW 264.7 , Ramnose , Rosa/classificação , Transdução de Sinais/efeitos dos fármacos , alfa-Amilases/antagonistas & inibidores , alfa-Glucosidases/metabolismo
16.
Int J Biol Macromol ; 170: 1-12, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33352155

RESUMO

In this study, novel quinazolinone derivatives 7a-n were synthesized and evaluated against metabolic enzymes including α-glycosidase, acetylcholinesterase, butyrylcholinesterase, human carbonic anhydrase I, and II. These compounds exhibited high inhibitory activities in comparison to used standard inhibitors with Ki values in the range of 19.28-135.88 nM for α-glycosidase (Ki value for standard inhibitor = 187.71 nM), 0.68-23.01 nM for acetylcholinesterase (Ki value for standard inhibitor = 53.31 nM), 1.01-29.56 nM for butyrylcholinesterase (Ki value for standard inhibitor = 58.16 nM), 10.25-126.05 nM for human carbonic anhydrase I (Ki value for standard inhibitor = 248.18 nM), and 13.46-178.35 nM for human carbonic anhydrase II (Ki value for standard inhibitor = 323.72). Furthermore, the most potent compounds against each enzyme were selected in order to evaluate interaction modes of these compounds in the active site of the target enzyme. Cytotoxicity assay of the title compounds 7a-n against cancer cell lines MCF-7 and LNCaP demonstrated that these compounds do not show significant cytotoxic effects.


Assuntos
Inibidores da Anidrase Carbônica/química , Inibidores da Colinesterase/química , Inibidores de Glicosídeo Hidrolases/química , Quinazolinonas/química , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/toxicidade , Inibidores da Anidrase Carbônica/síntese química , Inibidores da Anidrase Carbônica/farmacologia , Inibidores da Anidrase Carbônica/toxicidade , Linhagem Celular Tumoral , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/toxicidade , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/toxicidade , Humanos , Cinética , Células MCF-7 , Masculino , Simulação de Acoplamento Molecular , Estrutura Molecular , Neoplasias da Próstata/patologia , Quinazolinonas/síntese química , Quinazolinonas/farmacologia , Quinazolinonas/toxicidade , Relação Estrutura-Atividade , Especificidade por Substrato
17.
Carbohydr Polym ; 254: 117312, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33357875

RESUMO

Vitexin of Ficus deltoidea exhibits intestinal α-glucosidase inhibitory and blood glucose lowering effects. This study designs oral intestinal-specific alginate nanoparticulate system of vitexin. Nanospray-dried alginate, alginate/stearic acid and alginate-C18 conjugate nanoparticles were prepared. Stearic acid was adopted to hydrophobize the matrix and minimize premature vitexin release in stomach, whereas C-18 conjugate as immobilized fatty acid to sustain hydrophobic effect and drug release. Nanoparticles were compacted with polyethylene glycol (PEG 3000, 10,000 and 20,000). The physicochemical, drug release, in vivo blood glucose lowering and intestinal vitexin content of nanoparticles and compact were determined. Hydrophobization of alginate nanoparticles promoted premature vitexin release. Compaction of nanoparticles with PEG minimized vitexin release in the stomach, with stearic acid loaded nanoparticles exhibiting a higher vitexin release in the intestine. The introduction of stearic acid reduced vitexin-alginate interaction, conferred alginate-stearic acid mismatch, and dispersive stearic acid-induced particle breakdown with intestinal vitexin release. Use of PEG 10,000 in compaction brought about PEG-nanoparticles interaction that negated initial vitexin release. The PEG dissolution in intestinal phase subsequently enabled particle breakdown and vitexin release. The PEG compacted nanoparticles exhibited oral intestinal-specific vitexin release, with positive blood glucose lowering and enhanced intestinal vitexin content in vivo.


Assuntos
Alginatos/química , Apigenina/administração & dosagem , Proteínas de Bactérias/administração & dosagem , Toxinas Bacterianas/administração & dosagem , Glicemia/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Portadores de Fármacos/química , Inibidores de Glicosídeo Hidrolases/administração & dosagem , Proteínas Hemolisinas/administração & dosagem , Hipoglicemiantes/administração & dosagem , Nanopartículas/química , Administração Oral , Alginatos/metabolismo , Animais , Apigenina/química , Proteínas de Bactérias/química , Toxinas Bacterianas/química , Diabetes Mellitus Experimental/induzido quimicamente , Liberação Controlada de Fármacos , Ficus/química , Inibidores de Glicosídeo Hidrolases/química , Proteínas Hemolisinas/química , Ligação de Hidrogênio , Hipoglicemiantes/química , Masculino , Tamanho da Partícula , Polietilenoglicóis/metabolismo , Ratos , Ratos Sprague-Dawley , Ácidos Esteáricos/química , Estreptozocina/efeitos adversos , alfa-Glucosidases/metabolismo
18.
Int J Biol Macromol ; 169: 428-435, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33347933

RESUMO

In this study, we have investigated a series of hydroxylated 2-phenylbenzofurans compounds for their inhibitory activity against α-amylase and α-glucosidase activity. Inhibitors of carbohydrate degrading enzymes seem to have an important role as antidiabetic drugs. Diabetes mellitus is a wide-spread metabolic disease characterized by elevated levels of blood glucose. The most common is type 2 diabetes, which can lead to severe complications. Since the aggregates of islet amyloid polypeptide (IAPP) are common in diabetic patients, the effect of compounds to inhibit amyloid fibril formation was also determined. All the compounds assayed showed to be more active against α-glucosidase. Compound 16 showed the lowest IC50 value of the series, and it is found to be 167 times more active than acarbose, the reference compound. The enzymatic activity assays showed that compound 16 acts as a mixed-type inhibitor of α-glucosidase. Furthermore, compound 16 displayed effective inhibition of IAPP aggregation and it manifested no significant cytotoxicity. To predict the binding of compound 16 to IAPP and α-glucosidase protein complexes, molecular docking studies were performed. Altogether, our results support that the 2-phenylbenzofuran derivatives could represent a promising candidate for developing molecules able to modulate multiple targets involved in diabetes mellitus disorder.


Assuntos
Benzofuranos/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , alfa-Amilases/antagonistas & inibidores , Amiloide/química , Benzofuranos/química , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/metabolismo , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/metabolismo , Humanos , Hidroxilação , Hipoglicemiantes/farmacologia , Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Simulação de Acoplamento Molecular , Estudos Prospectivos , alfa-Amilases/química , alfa-Glucosidases/metabolismo
19.
Food Chem ; 345: 128808, 2021 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-33316712

RESUMO

Effects of 60Co-irradiation and superfine grinding wall disruption on the phenolic, antioxidant activity, and α-glucosidase-inhibiting potential of pine pollen were investigated. Eight soluble phenolics (SP) and insoluble-bound phenolic (IBP) compounds were characterized for the first time. After 60Co-irradiation, total phenolic content (TPC) and total flavonoid content (TFC) in SP increased by 16.90% and 14.66%, respectively; in IBP, they decreased by 53.26% and 21.57%, respectively; whereas they were unchanged in pine pollen, but antioxidant activity decreased by 29.18%-40.90%. After superfine grinding wall disruption, the TPC and TFC in IBP increased by 80.24% and 27.24%, respectively; in pine pollen, they increased by 22.66% and 10.61%, respectively; whereas they were unchanged in SP; and their antioxidant activity increased by 46.68%-58.06%. Both pretreatments had a little effect on the α-glucosidase-inhibiting activities of pine pollen. These results would be helpful in promoting the application of pine pollen in functional food.


Assuntos
Radioisótopos de Cobalto , Fenômenos Mecânicos , Fenóis/análise , Fenóis/farmacologia , Pinus/química , Pólen/química , Pólen/efeitos da radiação , Antioxidantes/análise , Antioxidantes/farmacologia , Manipulação de Alimentos , Inibidores de Glicosídeo Hidrolases/análise , Inibidores de Glicosídeo Hidrolases/farmacologia , Pinus/efeitos da radiação
20.
Food Chem ; 345: 128823, 2021 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-33341560

RESUMO

Ten new (1-10) and five known (11-15) ent-kaurane diterpene derivatives were identified from the roasted beans of coffea arabica. Their structures were established by extensive spectroscopic analysis including 1D, 2D NMR (HSQC, HMBC, COSY, and ROESY), HRESIMS, and X-ray diffraction analysis. Compounds 1-3 were three types of rearranged ent-kaurane diterpenes, and compounds 4 and 5 were diterpene esters with a rare 6-hydroxyhexanoyl at C-17. Compounds 6, 8, 14, and 15 showed moderate inhibitory effect on α-glucosidase with IC50 values of 149.92 ± 2.52, 23.23 ± 1.03, 54.58 ± 4.21, 54.16 ± 3.95 µM, respectively, compared to the positive control (60.71 ± 16.45 µM). The results of activity assay showed that diterpenes with the double bond between C-15 and C-16 exhibited stronger α-glucosidase inhibitory activity. Further molecular docking experiments were adopted to discuss the mechanism of activity.


Assuntos
Coffea/química , Diterpenos de Caurano/metabolismo , Diterpenos de Caurano/farmacologia , Inibidores de Glicosídeo Hidrolases/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Simulação de Acoplamento Molecular , alfa-Glucosidases/metabolismo , Culinária , Diterpenos de Caurano/química , Inibidores de Glicosídeo Hidrolases/química , Espectroscopia de Ressonância Magnética , Conformação Proteica , alfa-Glucosidases/química
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