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1.
Molecules ; 26(13)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201554

RESUMO

The Angiotensin-I-converting enzyme (ACE) is a peptidase with a significant role in the regulation of blood pressure. Within this work, a systematic review on the enzymatic preparation of Angiotensin-I-Converting Enzyme inhibitory (ACEi) peptides is presented. The systematic review is conducted by following PRISMA guidelines. Soybeans and velvet beans are known to have high protein contents that make them suitable as sources of parent proteins for the production of ACEi peptides. Endopeptidase is commonly used in the preparation of soybean-based ACEi peptides, whereas for velvet bean, a combination of both endo- and exopeptidase is frequently used. Soybean glycinin is the preferred substrate for the preparation of ACEi peptides. It contains proline as one of its major amino acids, which exhibits a potent significance in inhibiting ACE. The best enzymatic treatments for producing ACEi peptides from soybean are as follows: proteolytic activity by Protease P (Amano-P from Aspergillus sp.), a temperature of 37 °C, a reaction time of 18 h, pH 8.2, and an E/S ratio of 2%. On the other hand, the best enzymatic conditions for producing peptide hydrolysates with high ACEi activity are through sequential hydrolytic activity by the combination of pepsin-pancreatic, an E/S ratio for each enzyme is 10%, the temperature and reaction time for each proteolysis are 37 °C and 0.74 h, respectively, pH for pepsin is 2.0, whereas for pancreatin it is 7.0. As an underutilized pulse, the studies on the enzymatic hydrolysis of velvet bean proteins in producing ACEi peptides are limited. Conclusively, the activity of soybean-based ACEi peptides is found to depend on their molecular sizes, the amino acid residues, and positions. Hydrophobic amino acids with nonpolar side chains, positively charged, branched, and cyclic or aromatic residues are generally preferred for ACEi peptides.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/isolamento & purificação , Mucuna/metabolismo , Soja/metabolismo , Aminoácidos/química , Inibidores da Enzima Conversora de Angiotensina/química , Aspergillus/enzimologia , Endopeptidases/química , Exopeptidases/química , Globulinas/química , Hidrólise , Interações Hidrofóbicas e Hidrofílicas , Pancreatina/química , Peptídeo Hidrolases/química , Peptídeos/química , Prolina/química , Proteínas de Soja/química , Temperatura
2.
Food Funct ; 12(7): 2938-2949, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33710204

RESUMO

The aim of the study was to implement a gastric digestion step using recombinant human gastric lipase (rHGL) in an in vitro pediatric gastro-intestinal digestion model to achieve a physiologically relevant gastric contribution to total gastro-intestinal lipid digestion. A commercial infant formula (NAN Comfort stage 1 (NAN1)) with 3.4% lipid and an in-lab prepared oil-in-water emulsion, emulsified with soy phosphatidylcholine (SPCemul), with 3.5% lipid (oil-blend containing Akonino NS, MEG-3 and ARASCO oils) were subjected to in vitro gastro-intestinal digestion. To achieve a physiologically relevant level of gastric digestion, 50 min of in vitro gastric digestion, using either 0, 3.75 or 7.5 TBU mL-1 rHGL, was followed by 90 min of in vitro intestinal digestion, using either 0 or 26.5 TBU mL-1 pancreatic triglyceride lipase (PTL) from porcine pancreatin. The digestion of the substrates was assessed using titration-based quantification supported by HPLC-ELSD analysis. In vitro gastric digestion of NAN1 and SPCemul with either 3.75 or 7.5 TBU mL-1 rHGL contributed with 10-27% of the total gastro-intestinal digestion, corresponding to the reported contribution in human infants. At the end of the gastro-intestinal digestion (t = 140 min), the combined lipolytic effect of rHGL and PTL was additive during digestion of SPCemul, but not for the digestion of NAN1, as all lipase activity combinations resulted in a similar degree of NAN1 digestion. The effect of gastric digestion with rHGL on total digestion therefore appeared to be substrate dependent. To conclude, a gastric digestion step using rHGL resulting in physiologically relevant gastric contribution to the observed gastro-intestinal digestion was successfully implemented into an in vitro pediatric gastro-intestinal digestion model.


Assuntos
Digestão/efeitos dos fármacos , Alimentos Infantis , Lipase/farmacologia , Pancreatina/farmacologia , Humanos , Lactente , Recém-Nascido
3.
Food Chem ; 350: 129188, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33588280

RESUMO

Hempseed meal after protein isolation (HM-PI) is a co-product obtained from hempseed. The objectives were to characterize and determine the effect of drying on HM-PI. HM-PI was produced using three drying methods: freeze (FD), vacuum oven (VOD), and oven drying (OD). HM-PI contained over 70% protein and had similar or higher level of essential amino acids than recommended values for human adults. Osborne fractionation indicated that glutelin was the most dominant fraction in HM-PI. FD HMPI has a significant lower surface hydrophobicity and higher in vitro protein digestibility than OD and VOD HM-PI. FD HM-PI demonstrated better functional properties than OD and VOD HM-PI. Pepsin-pancreatin digestion of VOD, FD and OD resulted in comparable and considerable antioxidant and anti-inflammatory properties. This is the first report on the characterization of HM-PI, a co-product of hempseed processing. HM-PI could serve as a novel food protein ingredient resulting in increase utilization of hempseed.


Assuntos
Cannabis/química , Fenômenos Químicos , Dessecação/métodos , Resinas Vegetais/química , Antioxidantes/análise , Liofilização , Humanos , Pancreatina/metabolismo , Pepsina A/metabolismo , Resinas Vegetais/isolamento & purificação , Resinas Vegetais/metabolismo
4.
Artigo em Inglês | MEDLINE | ID: mdl-33546159

RESUMO

Primary cell cultures from wild organisms have been gaining relevance in ecotoxicology as they are considered more sensitive than immortalized cell lines and retain the biochemical pathways found in vivo. In this study, the efficacy of two methods for primary hepatocyte cell isolation was compared using liver from two marine fish (Sparus aurata and Psetta maxima): (i) two-step collagenase perfusion and (ii) pancreatin digestion with modifications. Cell cultures were incubated in L-15 medium at 17 ± 1 °C and monitored for up to six days for cell viability and function using the trypan blue exclusion test, MTT test, lactate dehydrogenase (LDH) activity, and ethoxyresorufin O-deethylase (EROD) activity after Benzo[a]Pyrene exposure. The results showed significant differences between the number of viable cells (p < 0.05), the highest number being obtained for the pancreatin digestion method (average = 4.5 ± 1.9 × 107 cells). Moreover, the hepatocytes showed solid adherence to the culture plate and the rounded shape, changing into a triangular/polygonal shape. The cell viability and function obtained by pancreatin digestion were maintained for five days, and the EROD induction after exposure to the B[a]P showed that cells were metabolically active. This study shows that the optimized pancreatin digestion method is a valid, cost-effective, and simple alternative to the standard perfusion method for the isolation of primary hepatocytes from fish and is suitable for ecotoxicological studies involving marine pollutants, such as PAHs.


Assuntos
Hepatócitos , Pancreatina , Animais , Técnicas de Cultura de Células , Citocromo P-450 CYP1A1 , Digestão , Transtornos Dissociativos , Linguados , Fígado , Dourada
5.
Plant Foods Hum Nutr ; 76(1): 31-36, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33245466

RESUMO

Vegetable by-products, obtained from cauliflower (CA), broccoli (BRL), cabbage (CB) and beetroot (BR) can be a potentially good source of proteins. The proteins were obtained from leaves (LPs) of vegetables with alkaline extraction at pH 10, and their isoelectric precipitation at pH 4. Protein contents were in the range of 39.76 - 53.33%, and the molecular weights of fractions were mostly about 45, 25 and 14 kDa. Their solubility is higher in the alkaline environment, where they reach the highest solubility at pH 10 (9.7 mg/mL for CALP, 8.45 for BRLP, 5.35 mg/mL for CBLP, 5.5 mg/mL for BELP). Moreover, they showed favorable emulsifying abilities, water absorption capacities (0.62 to 1.61 g/g) and foaming capacity (86.3 to 92%) as well as stability (48.57 to 79.30%). Digestibility was studied using gastrointestinal proteases (pepsin and pancreatin), and all four LPs can easily be digested. The biologically active potential of the digests was evaluated measuring antioxidant capacity by two complementary methods - DPPH+ and ABTS+ radical cation scavenging activity. The values for DPPH+ and ABTS+ were in the range from 59 to 65.1% at 0.1 and 0.3 mg/ml to 0.22 mg/ml IC50 values, respectively. Therefore, it can be indicated from these results, that obtained LPs, owing to their good functional properties, may be considered as potential ingredients of health-promoting food and cosmetic products.


Assuntos
Antioxidantes , Verduras , Pancreatina , Pepsina A , Solubilidade
6.
Food Chem ; 342: 128387, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33097324

RESUMO

Salmon is the main dietary source of omega-3 lipids and contains high-biological value protein. However, processing techniques could affect macronutrient digestibility. Also, altered intestinal conditions, particularly given in pancreatic insufficiency, could threaten digestibility. This study tested both hypotheses by subjecting raw, marinated and microwave-cooked salmon to static in vitro digestion under healthy (pH 7, bile concentration 10 mM) and altered (pH 6, bile 1 or 10 mM) intestinal conditions with different pancreatin concentrations. In the standard conditions, proteolysis was not affected by processing, but lipolysis decreased in marinated (46%) and raw salmon (57%) compared to the cooked matrix (67%). In altered conditions, proteolysis and lipolysis decreased to different extents depending on the treatment. Overall, processing affected proteolysis the most (f-ratio = 5.86), while intestinal conditions were the major determinants of lipolysis (f-ratio = 58.01). This study could set the ground to establish dietary recommendations of salmon for specific population groups.


Assuntos
Manipulação de Alimentos/métodos , Nutrientes/metabolismo , Salmão/metabolismo , Alimentos Marinhos/análise , Animais , Digestão , Concentração de Íons de Hidrogênio , Lipólise , Espectroscopia de Ressonância Magnética , Pancreatina/análise , Pancreatina/metabolismo , Proteólise
7.
Food Chem ; 343: 128394, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33097329

RESUMO

Amaranth (Amaranthus hypochondriacus) is an ancestral nutritional grain and good source of bioactive compounds as peptides. In this study, the effect of in vitro simulated gastrointestinal digestion (SGD) of germinated amaranth on the release of antioxidant and anti-inflammatory peptides was evaluated. The germinated amaranth peptides generated during SGD were released after 90 min of incubation with pancreatin and fractioned to F1 (>10 kDa), F2 (3-10 kDa), and F3 (<3 kDa). Among germinated amaranth peptides fractions tested, F2 had the highest antioxidant activity, while F1 and F2 exhibited a high anti-inflammatory response caused by lipopolysaccharide-induced in RAW 264.7 macrophages. A total of 11 peptides sequences were identified in the fractions evaluated, and they exhibit potential biological activity against non-communicable diseases. The findings from this study showed first time report on bioactive peptides, especially anti-inflammatory, from germinated amaranth released by in vitro gastrointestinal digestion.


Assuntos
Amaranthus/metabolismo , Anti-Inflamatórios/química , Antioxidantes/química , Peptídeos/química , Amaranthus/crescimento & desenvolvimento , Animais , Anti-Inflamatórios/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Digestão , Germinação , Lipopolissacarídeos/toxicidade , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Pancreatina/metabolismo , Peptídeos/metabolismo , Peptídeos/farmacologia , Células RAW 264.7
8.
Drugs R D ; 20(4): 369-376, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33211277

RESUMO

BACKGROUND: Pancreatic enzyme-replacement therapy (PERT), provided as pancreatin to patients with pancreatic exocrine insufficiency (PEI), is considered an essential substitute for the pivotal physiological function the pancreas fulfills in digestion. PEI involves a reduction in the synthesis and secretion of pancreatic enzymes (lipase, protease, amylase), which leads to an inadequate enzymatic response to a meal and consequently to maldigestion and malabsorption of nutrients. The efficacy of PERT is strongly dependent on enzyme activity, dissolution, and pancreatin particle size. OBJECTIVE: The physiological properties of eight pancreatin preparations (nine batches; five different brands) available in Russia and CIS (Commonwealth of Independent States: Armenia, Azerbaijan, Belarus, Kazakhstan, Kyrgyzstan, Moldova, Russia, Tajikistan, Uzbekistan) were investigated. METHODS: The lipase activity, dissolution, and particle size distribution of samples from multiple batches of pancreatin of different strengths were measured. RESULTS: Regarding lipase activities, all pancreatin preparations except Micrazim® matched the labeled content. Considerable differences were observed in particle size and dissolution. CONCLUSION: Pancreatin preparations available in Russia and CIS demonstrate product-to-product and batch-to-batch variability regarding the measured properties of lipase activity, dissolution, and particle size. This may impact the efficacy of PERT and therefore clinical outcomes.


Assuntos
Fármacos Gastrointestinais/química , Fármacos Gastrointestinais/metabolismo , Lipase/análise , Lipase/metabolismo , Pancreatina/química , Pancreatina/metabolismo , Comunidade dos Estados Independentes , Liberação Controlada de Fármacos , Insuficiência Pancreática Exócrina/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Humanos , Pancreatina/uso terapêutico , Tamanho da Partícula , Preparações Farmacêuticas/análise , Preparações Farmacêuticas/química , Federação Russa
9.
Nutrients ; 12(10)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33007855

RESUMO

Phosphorylated proteins from food sources have been investigated as regulators of bone formation with potential benefits in treating osteoporosis. Egg, a cheap and nutritious food, is also the source of various proteins and bioactive peptides with applications in human health. Egg yolk is rich in phosvitin, the most phosphorylated protein in nature. Phosvitin has been shown to improve bone health in experimental animals, although the molecular mechanisms and its specific effects on bone-forming osteoblastic cells are incompletely understood. Previous work in our group has identified pancreatin-generated phosvitin phospho-peptides (PPP) as a potential source for bioactive peptides. Given this background, we examined the roles of both phosvitin and PPP in the function of osteoblastic cells. Our results demonstrated their potential to improve bone health by promoting osteoblast differentiation and proliferation, suppressing osteoclast recruitment and the deposition of extracellular matrix, although PPP appeared to demonstrate superior osteogenic functions compared to phosvitin alone.


Assuntos
Proteínas do Ovo/química , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Fosfopeptídeos/química , Fosvitina/farmacologia , Células 3T3 , Animais , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Camundongos , Pancreatina/metabolismo , Fosforilação , Fosvitina/química
10.
Molecules ; 25(20)2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33066429

RESUMO

The present study assessed the effect of pretreating beef as a raw material for sous vide steak preparation. The pretreatment involved maceration of a batch of meat in sour milk with the simultaneous use of ultrasound (250 or 500 W) as well as the addition of Taraxacum officinale. The biological activity profile of the peptides was assessed in terms of their antioxidant activity and inhibiting activity against angiotensin-converting enzyme (ACE). Changes in the biological activity of peptides under the influence of hydrolysis by gastrointestinal enzymes, i.e., pepsin and pancreatin, were also considered. There was no significant effect of T. officinale addition and sonication of beef batches on the protein content (except for lot S6, after sonication at 500 W as acoustic power and with the addition of dandelion). It was observed that the interaction of maceration in sour milk with simultaneous ultrasound treatment as the initial production step of sous vide beef steak generates the formation of peptides with antioxidant properties. Moreover, peptide formation can be further enhanced by adding dandelion (based on the results of antiradical and chelating activity tests). In addition, the progression of hydrolysis under the influence of gastrointestinal enzymes promotes the release of peptides with antioxidant and anti-ACE activity.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Proteínas Animais da Dieta/farmacologia , Antioxidantes/farmacologia , Leite , Carne Vermelha , Inibidores da Enzima Conversora de Angiotensina/química , Proteínas Animais da Dieta/química , Animais , Antioxidantes/química , Fermentação , Hidrólise , Pancreatina/química , Pepsina A/química , Sonicação , Taraxacum/química
11.
J Food Sci ; 85(10): 3160-3167, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32885425

RESUMO

Functional evaluation of encrypted bioactive peptides in protein structure helps to better understand those for using in pharmacy and food sciences. For this purpose, the total protein was extracted from Matricaria chamomilla, Ziziphora clinopodioides, and Cressa cretica, and partially purified with ammonium sulfate. Protein hydrolysates were obtained from pancreatin hydrolysis for 240 min and the enzyme hydrolysis was confirmed using the determination of hydrolysis degree and Fourier transform infrared (FT-IR) followed by the physicochemical and sensory properties were investigated. The results showed that all hydrolysates had both cytotoxic and antioxidant activities. Specifically, C. cretica hydrolysates represented cytotoxic activity against the MCF-7 cell line with the IC50 of 135.21 µg/mL, while showed no significant growth inhibition effect on the HEK293 cell line. Besides, M. chamomilla hydrolysates showed the lowest bitterness value (1.125 ± 0.52). From the perspective of color investigation, M. chamomilla hydrolysates indicated the highest L* and the lowest a* factors. The highest turbidity and surface tension, and 10-fold more cancer cell killing effect under gastrointestinal digestion conditions were observed for M. chamomilla hydrolysates. Therefore, bioactive peptides might be formulated in designing of novel anticancer drugs or could be used in promising protocols for the production of food products with beneficial health effects.


Assuntos
Brassicaceae/química , Lamiaceae/química , Matricaria/química , Proteínas de Plantas/química , Antioxidantes/química , Antioxidantes/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células HEK293 , Humanos , Hidrólise , Pancreatina/química , Peptídeos/química , Peptídeos/farmacologia , Proteínas de Plantas/farmacologia , Plantas Medicinais/química , Hidrolisados de Proteína/química , Hidrolisados de Proteína/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier
12.
J Am Coll Surg ; 231(6): 658-669, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32927075

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a complication of pancreaticoduodenectomy (PD). We conducted a randomized clinical trial to determine if high-dose digestive enzymes prevented the development of NAFLD after PD. STUDY DESIGN: This parallel-group, nonblinded, multicenter study enrolled patients undergoing elective PD at Shinshu University School of Medicine, from June 2011 to April 2017. Patients were randomly assigned to receive normal-dose (Excelase: 3.0 g/day [Meiji Seika Pharma Holdings Co, Ltd]) or high-dose digestive enzyme treatment (Excelase: 3.0 g/day; Pancreatin [Tokyo Chemical Industry Co Ltd]: 3.0 g/day; Berizym [Kyowa Pharmaceutical Industry Co Ltd]: 3.0 g/day; and Toughmac-E [Ono Pharmaceutical Co, Ltd]: 3.0 g/day) within 1 week after surgery. Because patients in the control group switched interventions upon receiving a diagnosis of NAFLD, intention-to-treat analysis was used. The primary endpoint was incidence of NAFLD within 1 year, and the secondary endpoints were the incidences of NAFLD at 1, 3, 6, and 12 months and the rate of improvement in NAFLD with high-dose transfer in the control group. The secondary analysis comprised assessment of risk factors for the development of NAFLD. RESULTS: Eighty-four patients were randomly assigned (42 per group), 80 of whom were finally analyzed (39 normal-dose, 41 high-dose). The incidence of NAFLD was significantly lower in the high-dose (8 of 41) compared with the normal-dose (25 of 39) patients (p < 0.001). Multivariate analysis identified normal-dose (odds ratio [OR] 14.65, p < 0.001), total protein ≤ 6.5g/dL (OR 9.01, p = 0.018), pre-albumin ≤ 22.0 mg/dL (OR 7.71, p = 0.018), and pancreatic function diagnostic test ≤ 70% (OR 6.66, p = 0.009) as independent risk factors. There were no adverse effects. The model was accurate (c-index = 0.92) and reliable (Hosmer-Lemeshow test p = 0.32). CONCLUSIONS: High-dose administration of digestive enzymes significantly reduced the onset of NAFLD after PD compared with normal-dose administration. Registration number: UMIN000005595 (http://www.umin.ac.jp/ctr/).


Assuntos
Fármacos Gastrointestinais/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Pancreaticoduodenectomia/efeitos adversos , Idoso , Feminino , Fármacos Gastrointestinais/administração & dosagem , Humanos , Masculino , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Extratos Pancreáticos/administração & dosagem , Extratos Pancreáticos/uso terapêutico , Pancreaticoduodenectomia/métodos , Pancreatina/administração & dosagem , Pancreatina/uso terapêutico , Cuidados Pós-Operatórios/métodos
13.
PLoS Biol ; 18(7): e3000564, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32701952

RESUMO

Amyloids are protein aggregates with a highly ordered spatial structure giving them unique physicochemical properties. Different amyloids not only participate in the development of numerous incurable diseases but control vital functions in archaea, bacteria and eukarya. Plants are a poorly studied systematic group in the field of amyloid biology. Amyloid properties have not yet been demonstrated for plant proteins under native conditions in vivo. Here we show that seeds of garden pea Pisum sativum L. contain amyloid-like aggregates of storage proteins, the most abundant one, 7S globulin Vicilin, forms bona fide amyloids in vivo and in vitro. Full-length Vicilin contains 2 evolutionary conserved ß-barrel domains, Cupin-1.1 and Cupin-1.2, that self-assemble in vitro into amyloid fibrils with similar physicochemical properties. However, Cupin-1.2 fibrils unlike Cupin-1.1 can seed Vicilin fibrillation. In vivo, Vicilin forms amyloids in the cotyledon cells that bind amyloid-specific dyes and possess resistance to detergents and proteases. The Vicilin amyloid accumulation increases during seed maturation and wanes at germination. Amyloids of Vicilin resist digestion by gastrointestinal enzymes, persist in canned peas, and exhibit toxicity for yeast and mammalian cells. Our finding for the first time reveals involvement of amyloid formation in the accumulation of storage proteins in plant seeds.


Assuntos
Amiloide/metabolismo , Ervilhas/metabolismo , Proteínas de Armazenamento de Sementes/metabolismo , Sementes/metabolismo , Amiloide/ultraestrutura , Detergentes/farmacologia , Escherichia coli/metabolismo , Íons , Pancreatina/metabolismo , Ervilhas/efeitos dos fármacos , Pepsina A/metabolismo , Agregados Proteicos , Domínios Proteicos , Proteínas Recombinantes/química , Proteínas Recombinantes/farmacologia , Saccharomyces cerevisiae/metabolismo , Proteínas de Armazenamento de Sementes/química , Proteínas de Armazenamento de Sementes/farmacologia , Proteínas de Armazenamento de Sementes/ultraestrutura
14.
Food Funct ; 11(7): 6038-6053, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32558864

RESUMO

The effect of binding of flavonoids, (-)-epigallocatechin-3-gallate (EGCG) and green tea extract (GTE), to beta-lactoglobulin (ß-Lg) and micellar casein (micellar casein isolate, MCI) on protein digestibility was investigated. ß-Lg resisted digestion by pepsin, but in the presence of EGCG the digestion of ß-Lg was enhanced. Binding of EGCG to ß-Lg was identified by nitro blue tetrazolium (NBT) staining and found, by isothermal titration calorimetry, to be an enthalpy-driven exothermic process, with a binding constant of 19 950 L mol-1. Binding promoted a more rapid digestion of ß-Lg during simulated upper duodenal digestion. NBT staining indicated a loss of binding of EGCG to ß-Lg during combined gastric and distal small intestinal digestion and correlated with the cleavage of ß-Lg. However, increased ß-Lg heteromer formation and reduced ß-Lg monomer digestibility were observed for the ß-Lg-GTE complex. MCI was more digestible than ß-Lg during pepsin digestion, but reduced digestibility was observed for both MCI-EGCG and MCI-GTE complexes, with loss of binding during intestinal digestion. The free radical scavenging capacity (FRSC) of EGCG remained stable for the ß-Lg-EGCG complex throughout the gastric and intestinal phases of digestion, but this was significantly lowered for the MCI-EGCG complex. These results indicated that polyphenols bind to milk proteins modulating the in vitro digestibility and FRSC of ß-Lg and MCI as a result of the formation of complexes.


Assuntos
Antioxidantes , Camellia sinensis/química , Caseínas/metabolismo , Catequina/análogos & derivados , Flavonoides/farmacologia , Interações Alimento-Droga , Lactoglobulinas/metabolismo , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Catequina/farmacologia , Dieta , Proteínas na Dieta/metabolismo , Digestão , Humanos , Micelas , Pancreatina/metabolismo , Pepsina A/metabolismo , Extratos Vegetais/farmacologia , Polifenóis , Ligação Proteica , Chá/química
15.
Ter Arkh ; 92(1): 30-35, 2020 Jan 15.
Artigo em Russo | MEDLINE | ID: mdl-32598660

RESUMO

AIM: The goal is to evaluate the effectiveness of pancreatic enzyme replacement therapy (PERT) using microencapsulated pancreatin preparations for the correction of nutritional status in patients with chronic pancreatitis (CP) and associated exocrine pancreatic insufficiency (EPI). MATERIALS AND METHODS: The study included 58 patients with CP who were divided into two groups depending on the results of a laboratory assessment of indicators of nutritional status: group I (n=30) consisted of patients with CP and signs of EPI (according to low elastase test values) without deviations in nutritional status; Group II (n=28) consisted of patients with CP with a EPI and an abnormal nutritional status. In both groups, patients during the entire observation period (8-12 months) received PERT using microencapsulated pancreatin preparations at a dose adjusted for the severity of permanent residence permit. Before and after the PERT course, the dynamics of anthropometric [body weight, body mass index (BMI)] and laboratory indicators of nutritional status (total protein, albumin, vitamins D and B12, transferrin, iron and magnesium) were evaluated. RESULTS: After the completion of PERT, a significant tendency towards an increase in BMI in patients was noted in both groups. In group I, this indicator increased from 21.45 [95% confidence interval (CI) 19.80-23.92] kg/m2 to 22.15 (95% CI 20.31-23.86) kg/m2, and in II group - from 19.22 (95% CI 18.33-21.99) kg/m2 to 22.0 (95% CI 19.97-24.08) kg/m2. At the same time, the duration of PERT (months) significantly correlated with the dynamics of the patient's body weight (r=0.4679; 95% CI 0.2384-0.6479, p=0.0002). When assessing laboratory markers of nutritional status after PERT, a general tendency was found to increase the levels of total protein, albumin, vitamin D, magnesium, transferrin, and iron in both groups, however, statistically significant differences in the dynamics were observed mainly in group II patients. So, the level of total protein in group II increased from 69.05 (95% CI 65.6717-70.9000) g/l to 72.8 (95% CI 71.1358-74.9000) g/l, vitamin D - from 10.6 (95% CI 32.8397-38.9603) ng/ml to 17.1 (95% CI 12.0166-23.6232) ng/ml, magnesium - from 0.72 ( 95% CI 0.6892-0.7825) mmol/L to 0.795 (95% CI 0.7692-0.8800) mmol/L, and transferrin from 2.91 (95% CI 2.1800-3.3656 ) g/l to 2.92 (95% CI 2.4000-3.5200) g/l. CONCLUSION: A prospective observational study demonstrated the effectiveness of PERT using microencapsulated pancreatin preparations in the correction of nutritional status in patients with CP.


Assuntos
Insuficiência Pancreática Exócrina/tratamento farmacológico , Pancreatite Crônica/tratamento farmacológico , Terapia de Reposição de Enzimas , Humanos , Estado Nutricional , Pancreatina/uso terapêutico
16.
Pharm Res ; 37(6): 99, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32435855

RESUMO

PURPOSE: To evaluate the performance of artificial membranes in in vitro lipolysis-permeation assays useful for absorption studies of drugs loaded in lipid-based formulations (LBFs). METHODS: Polycarbonate as well as PVDF filters were treated with hexadecane, or lecithin in n-dodecane solution (LiDo) to form artificial membranes. They were thereafter used as absorption membranes separating two compartments mimicking the luminal and serosal side of the intestine in vitro. Membranes were subjected to dispersions of an LBF that had been digested by porcine pancreatin and spiked with the membrane integrity marker Lucifer Yellow (LY). Three fenofibrate-loaded LBFs were used to explore the in vivo relevance of the assay. RESULTS: Of the explored artificial membranes, only LiDo applied to PVDF was compatible with lipolysis by porcine pancreatin. Formulation ranking based on mass transfer in the LiDo model exposed was the same as drug release in single-compartment lipolysis. Ranking based on observed apparent permeability coefficients of fenofibrate with different LBFs were the same as those obtained in a cell-based model. CONCLUSIONS: The LiDo membrane was able to withstand lipolysis for a sufficient assay period. However, the assay with porcine pancreatin as digestive agent did not predict the in vivo ranking of the assayed formulations better than existing methods. Comparison with a Caco-2 based assay method nonetheless indicates that the in vitro in vivo relationship of this cell-free model could be improved with alternative digestive agents.


Assuntos
Portadores de Fármacos/química , Fenofibrato/química , Lipídeos/química , Lipólise , Membranas Artificiais , Administração Oral , Adsorção , Alcanos/química , Animais , Bioensaio/métodos , Células CACO-2 , Digestão , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Excipientes/química , Fenofibrato/administração & dosagem , Humanos , Lecitinas/química , Modelos Biológicos , Pancreatina/metabolismo , Permeabilidade , Solubilidade , Suínos
17.
AAPS PharmSciTech ; 21(5): 146, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32435989

RESUMO

The objective of this work was to study the effect of the physiologically relevant enzymes pepsin, pancreatin, and the synthetic surfactant sodium lauryl sulfate (SLS) on the surface tension of the dissolution media and the solubility and dissolution of the weakly basic drug carvedilol. Compendial dissolution media and buffer solutions that simulate the gastrointestinal fluid, prepared with and without the addition of SLS, were used in this study. The surface tension of the dissolution media; critical micelle concentration (CMC) of SLS in buffer solutions; and size, polydispersity index, and zeta potential of SLS micelles loading carvedilol were determined. The solubility and dissolution of carvedilol were investigated and compared with those of the corresponding media prepared without the addition of pepsin, pancreatin, and SLS. Results showed that the addition of pepsin, pancreatin, and SLS lowered the surface tension of the dissolution media to 54.8, 55.7, and ~ 30 mN/m, respectively. The solubility of carvedilol was significantly enhanced with pepsin and SLS; however, no significant difference was found with pancreatin. The dissolution rate of carvedilol was fast in simulated gastric fluid with and without pepsin. The dissolution was further enhanced in media with pancreatin and SLS. The dissolution data were corroborated with the molar micellar solubilization (X) of SLS, ranging between 0.02 and 3.09. Understanding the effect of pepsin, pancreatin, and SLS on the surface tension of the dissolution media and the solubility and dissolution of poorly soluble drugs can improve our knowledge of the performance of these drugs in vivo.


Assuntos
Carvedilol/química , Dodecilsulfato de Sódio/farmacologia , Tensoativos/farmacologia , Micelas , Pancreatina/química , Pepsina A/química , Solubilidade , Tensão Superficial
18.
Pharm Res ; 37(4): 77, 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32236761

RESUMO

PURPOSE: Abiraterone acetate (AbA) is a poorly water-soluble drug with an oral bioavailability of <10% and a significant pharmaceutical food effect. We aimed to develop a more efficient oral solid-state lipid-based formulation for AbA using a supersaturated silica-lipid hybrid (super-SLH) approach to achieve high drug loading, improve in vitro solubilization and mitigate the food effect, while gaining a mechanistic insight into how super-SLH are digested and release drug. METHODS: The influence of super-SLH saturation level and lipid type on the physicochemical properties and in vitro solubilization during lipolysis of the formulations was investigated and compared to the commercial product, Zytiga. RESULTS: Super-SLH achieved significantly greater levels of AbA solubilization compared to Zytiga. Solubilization was influenced by the AbA saturation level, which determined the solid state of AbA and the relative amount of lipid, and the lipid utilized, which determined its degree of digestion and the affinity of the lipid and digestion products to the silica. A fine balance existed between achieving high drug loads using supersaturation and improving performance using the lipid-based formulation approach. The non-supersaturated SLH prepared with Capmul PG8 mitigated the 3-fold in vitro food effect. CONCLUSION: SLH and super-SLH improve in vitro solubilization of AbA, remove the food effect and demonstrate potential to improve oral bioavailability in vivo. Graphical Abstract Abiraterone acetate was formulated as silica-lipid hybrids and demonstrated enhanced in vitro solubilization in comparison to pure abiraterone acetate and commercial product, Zytiga.


Assuntos
Acetato de Abiraterona/química , Caprilatos/química , Composição de Medicamentos/métodos , Excipientes/química , Glicerídeos/química , Dióxido de Silício/química , Administração Cutânea , Disponibilidade Biológica , Digestão , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Interações Alimento-Droga , Humanos , Cinética , Lipólise , Pancreatina/química , Solubilidade , Propriedades de Superfície
19.
BMC Gastroenterol ; 20(1): 94, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32252649

RESUMO

BACKGROUND: Agenesis of the dorsal pancreas (ADP) is a very rare disease with no specific symptoms, and the pathogenesis is not clear. Some patients will be accompanied by other diseases, such as pancreatic tumor or pancreatitis. But most cases are very atypical and difficult to distinguish. Some syndromes of pancreatic exocrine insufficiency are common in patients with ADP. Here, we report two cases of ADP and summarize the clinical features, diagnosis, and treatment of ADP. CASE PRESENTATION: Case A is a 65-year-old Chinese woman who presented with abdominal pain accompanied by nausea, bloating and acid reflux. The enhanced abdominal CT scan found nothing meaningful except the absence of the body and tail of the pancreas. The diagnosis was considered as gastrointestinal dysfunction cause by exocrine pancreatic insufficiency and recovered after symptomatic treatment. Case B is a 61-year-old Chinese woman who presented with abdominal pain accompanied by fever, vomiting and bloating. The abdominal CT showed multiple stones in the gallbladder, and the body and tail of the patient's pancreas were absent. She was diagnosed with cholelithiasis and recovered after laparoscopic cholecystectomy. CONCLUSION: Agenesis of the dorsal pancreas (ADP) is a rare congenital disease with an unclear pathogenesis that presents multiple symptoms. It should be considered when the patients have non-specific, persistent and unexplained symptoms such as bloating or uncontrolled blood sugar. Imaging examination is helpful for diagnosis. And it does not require surgical intervention unless it accompanies other diseases, EPI need to be considered when the non-specific gastrointestinal symptoms appear.


Assuntos
Colecistite Aguda/diagnóstico , Colelitíase/diagnóstico , Anormalidades Congênitas/diagnóstico por imagem , Insuficiência Pancreática Exócrina/diagnóstico , Gastroenteropatias/diagnóstico , Pâncreas/anormalidades , Idoso , Colecistectomia Laparoscópica , Colecistite Aguda/complicações , Colecistite Aguda/cirurgia , Colelitíase/complicações , Colelitíase/cirurgia , Anormalidades Congênitas/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Terapia de Reposição de Enzimas , Insuficiência Pancreática Exócrina/complicações , Insuficiência Pancreática Exócrina/tratamento farmacológico , Insuficiência Pancreática Exócrina/fisiopatologia , Feminino , Fármacos Gastrointestinais/uso terapêutico , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/etiologia , Humanos , Hipoglicemiantes/uso terapêutico , Pessoa de Meia-Idade , Pâncreas/diagnóstico por imagem , Pâncreas/fisiopatologia , Pancreatina/uso terapêutico , Tomografia Computadorizada por Raios X
20.
Molecules ; 25(8)2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32316678

RESUMO

Staphylococcal enterotoxin A (SEA) functions both as superantigens that stimulate non-specific T cell proliferation as well as potent gastrointestinal toxins. We previously reported that (-)-epigallocatechin gallate (EGCG) binds to SEA. Therefore, the ability of EGCG to inhibit SEA toxin activity was examined. As a result, EGCG significantly decreased SEA-induced expression and production of interferon gamma (IFN-γ). In addition, EGCG inhibited SEA-induced spleen cell proliferation. To investigate the role of the galloyl group in EGCG on SEA cytotoxicity in more detail, the effect of the binding of a hydroxyl group at position 3 of the galloyl group in EGCG to SEA on SEA cytotoxicity was examined using two methylated EGCG. SEA cytotoxicity was significantly controlled in both (-)-3''-Me-EGCG and (-)-4''-Me-EGCG. These results suggest that EGCG inhibits toxic activity via direct interaction with SEA or without any interaction with SEA. The binding affinity between SEA and EGCG under in vivo conditions was examined using a model solution. Although after treatment under acidic and alkaline conditions, the presence of protein and the digestive tract model solution, EGCG still interacted with SEA. Our studies are the first to demonstrate the effect of the binding of EGCG to SEA on toxin activity.


Assuntos
Catequina/análogos & derivados , Enterotoxinas/toxicidade , Animais , Catequina/química , Catequina/farmacologia , Proliferação de Células/efeitos dos fármacos , Citocinas/biossíntese , Citocinas/genética , Interações Medicamentosas , Enterotoxinas/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Camundongos , Estrutura Molecular , Pancreatina , Pepsina A/farmacologia , Ligação Proteica
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