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1.
Yakugaku Zasshi ; 140(8): 1051-1061, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32741863

RESUMO

It has been reported that medium-chain triglyceride (MCT) have various physiological functions, such as anti-obesity and hypolipidemic effects. They can also elicit increased disaccharidase activity and intestinal cell proliferation. However, a meta-analysis of randomized controlled trials, comparing the effects of MCT on weight loss and body composition, detected commercial bias. Additional research on the physiological functions is needed in order to have conclusive evidence. Thus, we sought to evaluate the various functions of MCT by conducting a feeding study in rats. Rats fed a diet containing 15% (w/w) MCT, had significantly lower visceral fat weight, plasma and liver lipid concentrations; they had significantly higher intestinal maltase and glucoamylase activities; and they had a greater number of Ki-67 positive cells/crypt, compared to the rats fed a diet containing 15% (w/w) lard. The effects of a diet containing 5% (w/w) MCT was observed only for plasma cholesterol levels and the number of Ki-67 positive cells/crypt; in which some results were found to be inconsistent with previous reports. These results indicate that physiological functions of MCT are numerous and need to be confirmed by additional research.


Assuntos
Glucana 1,4-alfa-Glucosidase/metabolismo , Intestino Delgado/enzimologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Triglicerídeos/administração & dosagem , Triglicerídeos/farmacologia , alfa-Glucosidases/metabolismo , Animais , Fármacos Antiobesidade , Proliferação de Células/efeitos dos fármacos , Dieta , Hipolipemiantes , Intestino Delgado/citologia , Gordura Intra-Abdominal , Antígeno Ki-67/metabolismo , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos Sprague-Dawley , Triglicerídeos/química
2.
Food Chem ; 332: 127377, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32619942

RESUMO

In this study, paper spray ionization (PSI) coupled to high-resolution mass spectrometry has been used to identify secondary metabolites from ethanol extracts of Averrhoa carambola L. bark (ABE). Various phytoconstituents including phenolic acids, flavonoids, xanthones and terpenoids were identified from the bark. ABE shows potential antioxidant activity as well as markedly inhibited α-glucosidase, elastase, and tyrosinase enzyme activities in a concentration-dependent fashion, respectively. ABE significantly inhibited α-glucosidase at lower concentration (IC50: 7.15 ± 0.06 µg/mL). Identified compounds were tested to understand the biological activity of ABE. Experimental results suggest that norathyriol, one of the identified compounds, has significant α-glucosidase (IC50: 0.81 ± 0.01 µg/mL) inhibition and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities (IC50: 4.90 ± 0.09 µg/mL). At a dose of 100 mg/kg, ABE significantly decreased the postprandial blood glucose level in oral glucose tolerance test (OGTT). This study shows that carambola bark can be a potential source of bioactive compounds.


Assuntos
Antioxidantes/metabolismo , Averrhoa/metabolismo , Espectrometria de Massas , Metabolômica/métodos , Monofenol Mono-Oxigenase/metabolismo , Elastase Pancreática/metabolismo , alfa-Glucosidases/metabolismo
3.
PLoS One ; 15(7): e0236530, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32706831

RESUMO

Apple trees grafted on different rootstock types, including vigorous rootstock (VR), dwarfing interstock (DIR), and dwarfing self-rootstock (DSR), are widely planted in production, but the molecular determinants of tree branch architecture growth regulation induced by rootstocks are still not well known. In this study, the branch growth phenotypes of three combinations of 'Fuji' apple trees grafted on different rootstocks (VR: Malus baccata; DIR: Malus baccata/T337; DSR: T337) were investigated. The VR trees presented the biggest branch architecture. The results showed that the sugar content, sugar metabolism-related enzyme activities, and hormone content all presented obvious differences in the tender leaves and buds of apple trees grafted on these rootstocks. Transcriptomic profiles of the tender leaves adjacent to the top buds allowed us to identify genes that were potentially involved in signaling pathways that mediate the regulatory mechanisms underlying growth differences. In total, 3610 differentially expressed genes (DEGs) were identified through pairwise comparisons. The screened data suggested that sugar metabolism-related genes and complex hormone regulatory networks involved the auxin (IAA), cytokinin (CK), abscisic acid (ABA) and gibberellic acid (GA) pathways, as well as several transcription factors, participated in the complicated growth induction process. Overall, this study provides a framework for analysis of the molecular mechanisms underlying differential tree branch growth of apple trees grafted on different rootstocks.


Assuntos
Regulação da Expressão Gênica de Plantas , Malus/genética , Transdução de Sinais/genética , Açúcares/metabolismo , Ácido Abscísico/análise , Ácido Abscísico/metabolismo , Cromatografia Líquida de Alta Pressão , Citocininas/análise , Citocininas/metabolismo , Flores/genética , Flores/metabolismo , Giberelinas/análise , Giberelinas/metabolismo , Ácidos Indolacéticos/análise , Ácidos Indolacéticos/metabolismo , Malus/crescimento & desenvolvimento , Fenótipo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/metabolismo , Caules de Planta/genética , Caules de Planta/fisiologia , RNA de Plantas/genética , RNA de Plantas/metabolismo , Açúcares/análise , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , alfa-Glucosidases/genética , alfa-Glucosidases/metabolismo
4.
Food Chem ; 331: 127240, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-32585546

RESUMO

The present study focused on the phytochemical profiling along with evaluation of in vitro antioxidant, α-glucosidase and α-amylase inhibitory activities of various crudes and fractions obtained from Lepisanthes fruticosa (Roxb) Leenh fruit. Ethanolic seed crude extract exhibited the strongest radical scavenging, ß-carotene bleaching activity, α-glucosidase inhibition and the highest total phenolic content (TPC). Column chromatography afforded various fractions with fraction M4 being the most potent due to the strongest radical scavenging, ß-carotene bleaching, α-glucosidase inhibition and greatest amount of TPC. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of ethanolic seed crude extract and fraction M4 showed the presence of various phytochemicals with antioxidant and antidiabetic properties, which include mostly flavonoids and tannins. The results may suggest that the ethanolic crude seed extract and its fraction could be an excellent source of bioactive phytochemicals with antioxidant and antidiabetic potential.


Assuntos
Antioxidantes/química , Inibidores Enzimáticos/análise , Fenóis/análise , Extratos Vegetais/química , Sapindaceae/química , Cromatografia Líquida de Alta Pressão , Inibidores Enzimáticos/química , Flavonoides/análise , Flavonoides/química , Frutas/química , Frutas/metabolismo , Fenóis/química , Sapindaceae/metabolismo , Espectrometria de Massas em Tandem , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/metabolismo , alfa-Glucosidases/química , alfa-Glucosidases/metabolismo
5.
Biochem Soc Trans ; 48(3): 1287-1295, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32510142

RESUMO

The ongoing COVID-19 pandemic, caused by SARS-CoV-2, has pushed the health systems of many countries to breaking point and precipitated social distancing measures that have crippled economic activities across the globe. A return to normality is unlikely until effective therapeutics and a vaccine are available. The immediacy of this problem suggests that drug strategies should focus on repurposing approved drugs or late-stage clinical candidates, as these have the shortest path to use in the clinic. Here, we review and discuss the role of host cell N-glycosylation pathways to virus replication and the drugs available to disrupt these pathways. In particular, we make a case for evaluation of the well-tolerated drugs miglitol, celgosivir and especially miglustat for the treatment of COVID-19.


Assuntos
Antivirais/farmacologia , Betacoronavirus/química , Infecções por Coronavirus/metabolismo , Reposicionamento de Medicamentos/métodos , Inibidores de Glicosídeo Hidrolases/farmacologia , Pneumonia Viral/metabolismo , Antivirais/uso terapêutico , Calnexina/metabolismo , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Inibidores de Glicosídeo Hidrolases/uso terapêutico , Glicosilação/efeitos dos fármacos , Interações Hospedeiro-Patógeno , Humanos , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Dobramento de Proteína/efeitos dos fármacos , Glicoproteína da Espícula de Coronavírus/metabolismo , Replicação Viral/efeitos dos fármacos , alfa-Glucosidases/metabolismo
6.
J Med Chem ; 63(8): 4205-4214, 2020 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-32227946

RESUMO

Influenza and dengue viruses present a growing global threat to public health. Both viruses depend on the host endoplasmic reticulum (ER) glycoprotein folding pathway. In 2014, Sadat et al. reported two siblings with a rare genetic defect in ER α-glucosidase I (ER Glu I) who showed resistance to viral infections, identifying ER Glu I as a key antiviral target. Here, we show that a single dose of UV-4B (the hydrochloride salt form of N-(9'-methoxynonyl)-1-deoxynojirimycin; MON-DNJ) capable of inhibiting Glu I in vivo is sufficient to prevent death in mice infected with lethal viral doses, even when treatment is started as late as 48 h post infection. The first crystal structure of mammalian ER Glu I will constitute the basis for the development of potent and selective inhibitors. Targeting ER Glu I with UV-4B-derived compounds may alter treatment paradigms for acute viral disease through development of a single-dose therapeutic regime.


Assuntos
Dengue/prevenção & controle , Retículo Endoplasmático/efeitos dos fármacos , Inibidores de Glicosídeo Hidrolases/administração & dosagem , Influenza Humana/prevenção & controle , alfa-Glucosidases , Animais , Dengue/tratamento farmacológico , Dengue/enzimologia , Vírus da Dengue/efeitos dos fármacos , Vírus da Dengue/enzimologia , Relação Dose-Resposta a Droga , Retículo Endoplasmático/enzimologia , Humanos , Influenza Humana/tratamento farmacológico , Influenza Humana/enzimologia , Camundongos da Linhagem 129 , Camundongos Endogâmicos BALB C , Estrutura Secundária de Proteína , alfa-Glucosidases/metabolismo
7.
PLoS One ; 15(3): e0229734, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32126122

RESUMO

European honeybee, Apis mellifera, produces α-glucosidase (HBGase) that catalyzes the cleavage of an α-glycosidic bond of the non-reducing end of polysaccharides and has potential applications for malt hydrolysis in brewing industry. Characterized by their substrate specificities, HBGases have three isoforms including HBGase II, which prefers maltose to sucrose as a substrate. Previous study found that the catalytic efficiency of maltose hydrolysis of N226P mutant of HBGase II was higher than that of the wild type (WT), and the catalytic efficiency of maltose hydrolysis of WT was higher than those of H227Y and N226P-H227Y mutants. We hypothesized that N226P mutation probably caused maltose to bind with better affinity and position/orientation for hydrolysis than WT, while H227Y and N226P-H227Y mutations caused maltose to bind with worse affinity and position/orientation for hydrolysis than WT. Using this hypothesis, we performed molecular dynamics on the catalytically competent binding conformations of maltose/WT, maltose/N226P, maltose/H227Y, and maltose/N226P-H227Y complexes to elucidate effects of N226P and H227Y mutations on maltose binding in HBGase II active site. Our results reasonably support this hypothesis because the N226P mutant had better binding affinity, higher number of important binding residues, strong and medium hydrogen bonds as well as shorter distance between atoms necessary for hydrolysis than WT, while the H227Y and N226P-H227Y mutants had worse binding affinities, lower number of important binding residues and strong hydrogen bonds as well as longer distances between atoms necessary for hydrolysis than WT. Moreover, results of binding free energy and hydrogen bond interaction of residue 227 support the role of H227 as a maltose preference residue, as proposed by previous studies. Our study provides important and novel insight into how N226P and H227Y mutations affect maltose binding in HBGase II active site. This knowledge could potentially be used to engineer HBGase II to improve its efficiency.


Assuntos
Abelhas/enzimologia , Domínio Catalítico/genética , Proteínas de Insetos/genética , Maltose/metabolismo , alfa-Glucosidases/genética , Substituição de Aminoácidos , Animais , Abelhas/genética , Proteínas de Insetos/metabolismo , Simulação de Dinâmica Molecular , Mutação , Ligação Proteica/genética , Engenharia de Proteínas/métodos , Homologia de Sequência de Aminoácidos , Especificidade por Substrato/genética , alfa-Glucosidases/metabolismo
8.
Food Chem ; 317: 126346, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32070843

RESUMO

The inhibitory mechanisms of ferulic acid against α-amylase and α-glucosidase were investigated by enzyme kinetic analysis, circular dichroism (CD), Fourier-transform infrared (FT-IR) spectroscopy, fluorescence quenching and molecular docking. Results indicated that ferulic acid strongly inhibited α-amylase (IC50: 0.622 mg ml-1) and α-glucosidase (IC50: 0.866 mg ml-1) by mixed and non-competitive mechanisms, respectively. CD spectra and fluorescence intensity measurements confirmed that the secondary structure of α-amylase and α-glucosidase were changed and the microenvironments of certain amino acid residues were modulated by the binding of ferulic acid. FT-IR spectra indicated that the interaction between ferulic acid and α-amylase/α-glucosidase mainly involved in non-covalent bonds. Molecular docking further demonstrated that the interaction forces between ferulic acid and α-amylase/α-glucosidase were hydrogen bonds, with the binding energy of -5.30 to -5.10 and -5.70 kcal mol-1, respectively. This study might provide a theoretical basis for the designing of novel functional foods with ferulic acid.


Assuntos
Ácidos Cumáricos/metabolismo , Inibidores de Glicosídeo Hidrolases/metabolismo , alfa-Amilases/metabolismo , alfa-Glucosidases/metabolismo , Sítios de Ligação , Ácidos Cumáricos/química , Inibidores de Glicosídeo Hidrolases/química , Ligação de Hidrogênio , Cinética , Simulação de Acoplamento Molecular , Estrutura Secundária de Proteína , Termodinâmica , alfa-Amilases/química , alfa-Glucosidases/química
9.
Enzyme Microb Technol ; 134: 109479, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32044026

RESUMO

Mangiferin, a major constituent of Mangifera indica L., has attracted substantial attention due to its anti-oxidant, anti-diabetic, anti-inflammatory, and anti-microbial activities. However, its poor solubility in water limits its use in food and pharmaceutical industries. In this study, novel mangiferin-(1→6)-α-d-glucopyranoside (Mg-G1) was enzymatically synthesized from mangiferin and sucrose using glucansucrase from Leuconostoc mesenteroides B-512F/KM, and optimized using response surface methodology. The water solubility of Mg-G1 was found to be 824.7 mM, which is more than 2300-fold higher than that of mangiferin. Mg-G1 also showed DPPH radical scavenging activity and superoxide dismutase (SOD)-like scavenging activity, which were 4.77- and 3.71-fold higher than that of mangiferin, respectively. Mg-G1 displayed inhibitory activity against human intestinal maltase and COX-2. Thus, the novel glucosylated mangiferin may be used as an ingredient in functional food and pharmaceutical application.


Assuntos
Glucosídeos/biossíntese , Glicosiltransferases/metabolismo , Leuconostoc mesenteroides/enzimologia , Mangifera/química , Xantonas/metabolismo , Antioxidantes/metabolismo , Inibidores de Ciclo-Oxigenase 2/metabolismo , Humanos , Solubilidade , Sacarose/metabolismo , Superóxido Dismutase/metabolismo , alfa-Glucosidases/metabolismo
10.
Oxid Med Cell Longev ; 2020: 5363546, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32064026

RESUMO

The present study was performed to evaluate the antioxidant and intestinal protective effects of baicalin-copper on deoxynivalenol-challenged piglets. Forty weaned piglets were randomly divided into four groups and assigned to different diets: (1) basal diet (Con), (2) 4 mg/kg deoxynivalenol of basal diet (DON), (3) 5 g/kg baicalin-copper of basal diet (BCU); and (4) 4 mg/kg deoxynivalenol + 5 g/kg baicalin-copper of basal diet (DBCU). The results showed that the ADFI and ADG of piglets in the DON group were markedly lower than those in the Con group, but the ADFI and ADG of the DBCU group were not significantly different from those of the Con group. In piglets fed a DON-contaminated diet, dietary supplementation with BCU significantly decreased the mRNA levels of P70S6K, 4E-BP1, and HSP70 in the liver, the protein expression of HO-1 in the jejunum, and the expression of p-Nrf2 and p-NF-κB in the ileum but increased Mn-SOD activity in serum. Dietary supplementation with BCU increased jejunal maltase, ZIP4 and MT mRNA levels, and serum concentrations of Arg, Val, Ile, Leu, Lys, and Tyr in DON-contaminated piglets. In summary, BCU can alleviate the growth impairment induced by DON and enhance antioxidant capacity and nutrition absorption in piglets fed DON-contaminated diets.


Assuntos
Antioxidantes/metabolismo , Flavonoides/farmacologia , Íleo/efeitos dos fármacos , Jejuno/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Tricotecenos/toxicidade , Aminoácidos/sangue , Ração Animal , Animais , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Cobre/química , Dieta , Suplementos Nutricionais , Fator de Iniciação 4E em Eucariotos/genética , Fator de Iniciação 4E em Eucariotos/metabolismo , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Íleo/metabolismo , Jejuno/citologia , Jejuno/enzimologia , Jejuno/metabolismo , Fígado/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Estresse Oxidativo/genética , Proteínas Quinases S6 Ribossômicas 70-kDa/genética , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Soro/enzimologia , Soro/metabolismo , Superóxido Dismutase-1/sangue , Suínos , alfa-Glucosidases/genética , alfa-Glucosidases/metabolismo
11.
Curr Pharm Biotechnol ; 21(6): 467-479, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32065100

RESUMO

OBJECTIVE: The high cost of orphan drugs limits their access by many patients, especially in low- and middle-income countries. Many orphan drugs are off-patent without alternative generic or biosimilar versions available. Production of these drugs at the point-of-care, when feasible, could be a cost-effective alternative. METHODS: The financial feasibility of this approach was estimated by setting up a small-scale production of recombinant human acid alpha-glucosidase (rhGAA). The commercial version of rhGAA is Myozyme™, and Lumizyme™ in the United States, which is used to treat Pompe disease. The rhGAA was produced in CHO-K1 mammalian cells and purified using multiple purification steps to obtain a protein profile comparable to Myozyme™. RESULTS: The established small-scale production of rhGAA was used to obtain a realistic cost estimation for the magistral production of this biological drug. The treatment cost of rhGAA using bedside production was estimated at $3,484/gram, which is 71% lower than the commercial price of Myozyme ™. CONCLUSION: This study shows that bedside production might be a cost-effective approach to increase the access of patients to particular life-saving drugs.


Assuntos
Doença de Depósito de Glicogênio Tipo II/tratamento farmacológico , Produção de Droga sem Interesse Comercial/economia , Produção de Droga sem Interesse Comercial/métodos , Proteínas Recombinantes/isolamento & purificação , alfa-Glucosidases/isolamento & purificação , Animais , Células CHO , Cricetinae , Cricetulus , Custos de Medicamentos , Estudos de Viabilidade , Doença de Depósito de Glicogênio Tipo II/enzimologia , Humanos , Proteínas Recombinantes/economia , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , alfa-Glucosidases/economia , alfa-Glucosidases/genética , alfa-Glucosidases/metabolismo
12.
J Enzyme Inhib Med Chem ; 35(1): 565-573, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31969031

RESUMO

Embelin is a naturally occurring para-benzoquinone isolated from Embelia ribes (Burm. f.) of the Myrsinaceae family. It was first discovered to have potent inhibitory activity (IC50 = 4.2 µM) against α-glucosidase in this study. Then, four series of novel embelin derivatives were designed, prepared and evaluated in α-glucosidase inhibition assays. The results show that most of the embelin derivatives synthesised are effective α-glucosidase inhibitors, with IC50 values at the micromolar level, especially 10d, 12d, and 15d, the IC50 values of which are 1.8, 3.3, and 3.6 µM, respectively. Structure-activity relationship (SAR) studies suggest that hydroxyl groups in the 2/5-position of para-benzoquinone are very important, and long-chain substituents in the 3-position are highly preferred. Moreover, the inhibition mechanism and kinetics studies reveal that all of 10d, 12d, 15d, and embelin are reversible and mixed-type inhibitors. Furthermore, docking experiments were carried out to study the interactions between 10d and 15d with α-glucosidase.


Assuntos
Benzoquinonas/farmacologia , Desenho de Fármacos , Inibidores de Glicosídeo Hidrolases/farmacologia , alfa-Glucosidases/metabolismo , Benzoquinonas/síntese química , Benzoquinonas/química , Relação Dose-Resposta a Droga , Embelia/química , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/química , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade
13.
J Agric Food Chem ; 68(5): 1419-1426, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31888328

RESUMO

Sake, the Japanese rice wine, contains a variety of oligosaccharides and glucosides produced by fungal enzymes during the brewing process. This study investigates the effect of knocking out the Aspergillus oryzae α-glucosidase (agdA) gene on the transglycosylation products in brewed sake. In addition to α-ethyl glucoside and α-glyceryl glucoside, the amount of two compounds that have molecular mass values similar to that of ethyl maltose decreased by agdA gene knockout. Both compounds were synthesized, in vitro, from maltose and ethanol with purified agdA. Nuclear magnetic resonance analysis identified the two compounds as ethyl α-maltoside and ethyl α-isomaltoside, respectively, which are novel compounds in sake as well as in the natural environment. Quantitative analysis of 111 commercially available types of sake showed that these novel compounds were widely present at concentrations of several hundred mg/L, suggesting that both of them are ones of the common glycosides in sake.


Assuntos
Bebidas Alcoólicas/microbiologia , Aspergillus oryzae/enzimologia , Proteínas Fúngicas/metabolismo , Glicosídeos/metabolismo , alfa-Glucosidases/metabolismo , Bebidas Alcoólicas/análise , Aspergillus oryzae/genética , Aspergillus oryzae/metabolismo , Etanol/metabolismo , Fermentação , Proteínas Fúngicas/genética , Glicosídeos/química , Glicosilação , Maltose/metabolismo , Oryza/metabolismo , Oryza/microbiologia , alfa-Glucosidases/genética
14.
Phytochemistry ; 171: 112232, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31911266

RESUMO

Corni Fructus, also known as the fruit of Cornus officinalis Sieb. et Zucc., has long been used as a traditional Chinese medicine and is widely consumed as a nutritional food in the form of function drink and wine. Recently, Corni Fructus has attracted considerable interest because of its anti-diabetic effects. A systematic phytochemical investigation of Corni Fructus was performed to find anti-diabetic components, which led to the isolation of 10 unreported iridoid glycosides, cornusdiglycosides A-J (1-8, 9a/9b and 10a/10b). Their chemical structures were determined through spectroscopic analysis (ultraviolet [UV], infrared [IR], high-resolution electrospray ionisation mass spectroscopy [HRESIMS], one-dimensional [1D] and two-dimensional [2D] nuclear magnetic resonance [NMR]). Such morroniside-type diglycosides were first reported from natural sources, and all isolates were evaluated for α-glucosidase inhibitory activity. The results showed that all compounds (1-10) exhibited α-glucosidase (from Saccharomyces cerevisiae) inhibitory activities with IC50 values ranging from 78.9 ± 4.09 to 162.2 ± 9.17 µM, whereas acarbose, the positive control, displayed α-glucosidase inhibitory activity with IC50 value of 118.9 ± 7.89 µM.


Assuntos
Cornus/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Glicosídeos/farmacologia , Glucosídeos Iridoides/farmacologia , Compostos Fitoquímicos/farmacologia , alfa-Glucosidases/metabolismo , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Glicosídeos/química , Glicosídeos/isolamento & purificação , Humanos , Glucosídeos Iridoides/química , Glucosídeos Iridoides/isolamento & purificação , Conformação Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação
15.
Food Chem ; 313: 126099, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31927321

RESUMO

Diabetes mellitus is a metabolic disorder characterized by hyperglycemia, which can be counteracted by inhibition of α-glucosidase and α-amylase, both involved in the carbohydrate metabolism. Fourteen C-glucosidic ellagitannins and three galloylated glucoses were studied as potential α-glucosidase and α-amylase inhibitors. Most of the compounds were found to be moderate inhibitors of α-amylase, but potent inhibitors of α-glucosidase, showing low-micromolar IC50 values, far lower than that of the antidiabetic drug acarbose. This selectivity can be an advantage for their possible application as functional food ingredients with anti-diabetic properties because strong α-amylase inhibition generally causes undesired side effects. The best inhibitors were selected for further studies. Intrinsic fluorescence measurements confirmed their high affinity towards α-glucosidase, highlighting a static quenching mechanism. Circular dichroism measurements and kinetics of inhibition indicated that the most active C-glucosidic ellagitannin roburin D (RobD) is a competitive inhibitor, whereas α-pentagalloylglucose (α-PGG) acts as a mixed-type inhibitor.


Assuntos
Taninos Hidrolisáveis/química , Hipoglicemiantes/química , alfa-Amilases/metabolismo , alfa-Glucosidases/metabolismo , Dicroísmo Circular , Glucosídeos/química , Taninos Hidrolisáveis/metabolismo , Hipoglicemiantes/metabolismo , Concentração Inibidora 50 , Cinética , Espectrometria de Fluorescência , alfa-Amilases/antagonistas & inibidores , alfa-Glucosidases/química
16.
J Trace Elem Med Biol ; 58: 126448, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31901726

RESUMO

BACKGROUND: Increasing resistance to available drugs and their associated side-effects have drawn wide attention towards designing alternative therapeutic strategies for control of hyperglycemia and oxidative stress. The roles of the sizes and shapes of the nanomaterials used in the treatment and management of Type 2 Diabetes Mellitus (T2DM) in preventing chronic hyperglycaemia and oxidative stress are investigated. We report specifically on the effects of doping silver (Ag) into the ZnO nanorods (ZnO:Ag NR's) as a rational drug designing strategy. METHODS: Inhibition of porcine pancreatic α-amylase, murine pancreatic amylase, α-glucosidase, murine intestinal glucosidase and amyloglucosidase are checked for evaluation of antidiabetic potential. In addition, the radical scavenging activities of ZnO:Ag NR's against nitric oxide, DDPH and superoxide radicals are evaluated. RESULTS: Quantitative radical scavenging and metabolic enzyme inhibition activities of ZnO:Ag NR's at a concentration of 100 µg/mL were found to depend on the amount of Ag doped in up to a threshold level (3-4 %). Circular dichroism analysis revealed that the interaction of the NR's with the enzymes altered their secondary conformation. This alteration is the underlying mechanism for the potent enzyme inhibition. CONCLUSIONS: Enhanced inhibition of enzymes and scavenging of free radicals primarily responsible for reactive oxygen species (ROS) mediated damage, provide a strong scientific rationale for considering ZnO:Ag NR's as a candidate nanomedicine for controlling postprandial hyperglycaemia and the associated oxidative stress.


Assuntos
Antioxidantes/farmacologia , Hipoglicemiantes/farmacologia , Nanotubos/química , Prata/farmacologia , Óxido de Zinco/farmacologia , Amilases/antagonistas & inibidores , Amilases/metabolismo , Animais , Compostos de Bifenilo/química , Inibidores Enzimáticos/farmacologia , Depuradores de Radicais Livres/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Intestinos/enzimologia , Camundongos , Nanotubos/ultraestrutura , Óxido Nítrico/metabolismo , Pâncreas/enzimologia , Picratos/química , Superóxidos/metabolismo , Suínos , alfa-Glucosidases/metabolismo
17.
Int J Biol Macromol ; 148: 722-736, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31972201

RESUMO

The natural form of wild edible fungus is the fruiting body. The cultivation of fruiting bodies from sexual reproduction requires strict conditions and long periods. Some literatures have paid attentions on the mycelia prepared with liquid fermentation to alter fruiting bodies. Cordyceps militaris (C. militaris) is a kind of precious edible fungus. The polysaccharide is an important active ingredient in C. militaris. The manuscript aimed to evaluate the feasibility of alternative of mycelia to fruit bodies with studies of polysaccharides from C. militaris of different developmental stages. The two polysaccharides were separated. The chemical structure and inhibitory activity on α-glucosidase of polysaccharides were explored. The results indicated that the structure and inhibitory activity on α-glucosidase of polysaccharides with different developmental stages had significant differences. The polysaccharides from fruiting bodies had better inhibitory activity on α-glucosidase. It demonstrated that the mycelia of C. militaris from asexual reproduction with liquid fermentation can't be an effective substitute for fruiting bodies from sexual reproduction, from the perspective of polysaccharides.


Assuntos
Cordyceps/química , Inibidores de Glicosídeo Hidrolases/química , Polissacarídeos/química , alfa-Glucosidases/metabolismo , Fermentação , Carpóforos/química , Micélio/química , Conformação Proteica , Relação Estrutura-Atividade , Viscosidade
18.
Phytochemistry ; 170: 112192, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31726325

RESUMO

Chemical fractionation of the ethanolic extract of Eclipta prostrata yielded a series of unreported terpenoid constituents, including a rare 6/6/6/6-fused tetracyclic triterpenoid, a pentacyclic triterpenoid, two pentacyclic triterpenoid saponins, a diterpenoid and a sesquiterpenoid. Structures were assigned to these compounds on the basis of comprehensive spectroscopic analyses, with the absolute configurations of the tetracyclic triterpenoid, the diterpenoid and the sesquiterpenoid being determined via explanation of electronic circular dichroism data. Screening of these isolates in an array of bioassays revealed antibacterial, cytotoxic and α-glucosidase inhibitory activities for selective compounds. Of particular interest, the tetracyclic triterpenoid showed very strong inhibition against α-glucosidase with an IC50 of 0.82 ±â€¯0.18 µM, being 103-fold as active as the positive control acarbose.


Assuntos
Antibacterianos/farmacologia , Eclipta/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Neoplasias/tratamento farmacológico , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Terpenos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Bacillus subtilis/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Células HeLa , Humanos , Testes de Sensibilidade Microbiana , Neoplasias/patologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Staphylococcus aureus/efeitos dos fármacos , Terpenos/química , Terpenos/isolamento & purificação , alfa-Glucosidases/metabolismo
19.
Prep Biochem Biotechnol ; 50(2): 123-132, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31702433

RESUMO

The chemo-profiling of ethanolic extract of faba beans seeds was performed and explored as an α-glucosidase inhibitor. The inhibition of α-glucosidase is one of the alternatives approach to control postprandial hyperglycemia by, resulting in the delay of the carbohydrate digestion of absorbable monosaccharides. Ethanolic seed extract showed phenolic compounds, flavonoid such as gallic acid (m/z [M- H] = 169.0124,C7H6O5) ellagic acid derivatives epigallocatechin (m/z [M- H = 305.0644,C15H14O7),catechin (m/z [M- H] = 289.0656,C15H14O6), epigallocatechin gallate (m/z [M- H] = 457.0578,C22H18O11) and epicatechin monogallate (m/z [M- H] = 441.081, C22H18O10). The extract was found to exert inhibitory activity (88.28 ± 2.67%) (IC50 value of 2.30 ± 0.032 mg/mL) with a mixed mode of inhibition (Km, apparent = 0.54 ± 0.020 mM and Vmax, apparent 0.136 ± 0.04 mM/min). Molecular docking studies of gallic acid and catechin on α-glucosidase proposed productive binding modes having binding energy (-6.58 kcal/mol and -7.25 kcal/mol) with an effective number of hydrogen bonds and binding energy. Tyr63, Arg197, Asp198, Glu 233, Asn324, Asp 326 of α-glucosidase participated in binding events with gallic acid and catechin. Molecular dynamics simulation studies were performed for both complexes i.e. gal:α-glucosidase and cat:α-glucosidase along with apo state of α-glucosidase, which revealed stable systems during the simulation. These findings of the present study may give an insight into the further development of the novel antidiabetic drug from the seeds of faba beans.


Assuntos
Catequina/metabolismo , Ácido Gálico/metabolismo , Extratos Vegetais/farmacologia , Polifenóis/metabolismo , Vicia faba/metabolismo , alfa-Glucosidases/metabolismo , Cromatografia Líquida de Alta Pressão , Inibidores de Glicosídeo Hidrolases/farmacologia , Simulação de Acoplamento Molecular , Sementes/química , Espectrometria de Massas por Ionização por Electrospray , Vicia faba/embriologia
20.
Crit Rev Food Sci Nutr ; 60(4): 541-555, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30799629

RESUMO

Polyphenols, as one group of secondary metabolite, are widely distributed in plants and have been reported to show various bioactivities in recent year. Starch digestion not only is related with food industrial applications such as brewing but also plays an important role in postprandial blood glucose level, and therefore insulin resistance. Many studies have shown that dietary phenolic extracts and pure polyphenols can retard starch digestion in vitro, and the retarding effect depends on the phenolic composition and molecular structure. Besides, dietary polyphenols have also been reported to alleviate elevation of blood glucose level after meal, indicating the inhibition of starch digestion in vivo. This review aims to analyze how dietary polyphenols affect starch digestion both in vitro and in vivo. We can conclude that the retarded starch digestion in vitro by polyphenols results from inhibition of key digestive enzymes, including α-amylase and α-glucosidase, as well as from interactions between polyphenols and starch. The alleviation of postprandial hyperglycemia by polyphenols might be caused by both the inhibited starch digestion in vivo and the influenced glucose transport. Therefore, phenolic extracts or pure polyphenols may be alternatives for preventing and treating type II diabetes disease.


Assuntos
Glicemia/metabolismo , Digestão/efeitos dos fármacos , Polifenóis/administração & dosagem , Polifenóis/farmacologia , Amido/metabolismo , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/prevenção & controle , Humanos , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/metabolismo , alfa-Glucosidases/metabolismo
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