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1.
Front Immunol ; 12: 670955, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093569

RESUMO

The pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has led to an extraordinary threat to the global healthcare system. This infection disease, named COVID-19, is characterized by a wide clinical spectrum, ranging from asymptomatic or mild upper respiratory tract illness to severe viral pneumonia with fulminant cytokine storm, which leads to respiratory failure. To improve patient outcomes, both the inhibition of viral replication and of the unwarranted excessive inflammatory response are crucial. Since no specific antiviral drug has been proven effective for the treatment of patients and the only upcoming promising agents are monoclonal antibodies, inexpensive, safe, and widely available treatments are urgently needed. A potential anti-inflammatory molecule to be evaluated, which possesses antiviral activities in several experimental models, is the polyphenol resveratrol. This compound has been shown to inhibit SARS-CoV-2 replication in human primary bronchial epithelial cell cultures and to downregulate several pathogenetic mechanisms involved in COVID-19 severity. The use of resveratrol in clinical practice is limited by the low bioavailability following oral administration, due to the pharmacokinetic and metabolic characteristics of the molecule. Therefore, topical administration through inhaled formulations could allow us to achieve sufficiently high concentrations of the compound in the airways, the entry route of SARS-CoV-2.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Síndrome da Liberação de Citocina/tratamento farmacológico , Resveratrol/uso terapêutico , SARS-CoV-2 , Administração por Inalação , Animais , Anti-Inflamatórios/farmacocinética , Disponibilidade Biológica , COVID-19/imunologia , Síndrome da Liberação de Citocina/imunologia , Humanos , Resveratrol/farmacocinética
2.
Molecules ; 26(10)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064568

RESUMO

Resveratrol is a phytoalexin produced by many plants as a defense mechanism against stress-inducing conditions. The richest dietary sources of resveratrol are berries and grapes, their juices and wines. Good bioavailability of resveratrol is not reflected in its high biological activity in vivo because of resveratrol isomerization and its poor solubility in aqueous solutions. Proteins, cyclodextrins and nanomaterials have been explored as innovative delivery vehicles for resveratrol to overcome this limitation. Numerous in vitro and in vivo studies demonstrated beneficial effects of resveratrol in cardiovascular diseases (CVD). Main beneficial effects of resveratrol intake are cardioprotective, anti-hypertensive, vasodilatory, anti-diabetic, and improvement of lipid status. As resveratrol can alleviate the numerous factors associated with CVD, it has potential as a functional supplement to reduce COVID-19 illness severity in patients displaying poor prognosis due to cardio-vascular complications. Resveratrol was shown to mitigate the major pathways involved in the pathogenesis of SARS-CoV-2 including regulation of the renin-angiotensin system and expression of angiotensin-converting enzyme 2, stimulation of immune system and downregulation of pro-inflammatory cytokine release. Therefore, several studies already have anticipated potential implementation of resveratrol in COVID-19 treatment. Regular intake of a resveratrol rich diet, or resveratrol-based complementary medicaments, may contribute to a healthier cardio-vascular system, prevention and control of CVD, including COVID-19 disease related complications of CVD.


Assuntos
COVID-19/tratamento farmacológico , Doenças Cardiovasculares , Resveratrol , SARS-CoV-2/metabolismo , Disponibilidade Biológica , COVID-19/complicações , COVID-19/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Humanos , Resveratrol/farmacocinética , Resveratrol/uso terapêutico
3.
Int J Mol Sci ; 22(11)2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34073709

RESUMO

Polyphenols are natural organic compounds produced by plants, acting as antioxidants by reacting with ROS. These compounds are widely consumed in daily diet and many studies report several benefits to human health thanks to their bioavailability in humans. However, the digestion process of phenolic compounds is still not completely clear. Moreover, bioavailability is dependent on the metabolic phase of these compounds. The LogP value can be managed as a simplified measure of the lipophilicity of a substance ingested within the human body, which affects resultant absorption. The biopharmaceutical classification system (BCS), a method used to classify drugs intended for gastrointestinal absorption, correlates the solubility and permeability of the drug with both the rate and extent of oral absorption. BCS may be helpful to measure the bioactive constituents of foods, such as polyphenols, in order to understand their nutraceutical potential. There are many literature studies that focus on permeability, absorption, and bioavailability of polyphenols and their resultant metabolic byproducts, but there is still confusion about their respective LogP values and BCS classification. This review will provide an overview of the information regarding 10 dietarypolyphenols (ferulic acid, chlorogenic acid, rutin, quercetin, apigenin, cirsimaritin, daidzein, resveratrol, ellagic acid, and curcumin) and their association with the BCS classification.


Assuntos
Produtos Biológicos/metabolismo , Polifenóis/metabolismo , Animais , Disponibilidade Biológica , Produtos Biológicos/química , Produtos Biológicos/classificação , Produtos Biológicos/farmacocinética , Ácidos Cumáricos , Flavonas , Flavonóis , Humanos , Absorção Intestinal , Isoflavonas , Permeabilidade , Polifenóis/química , Polifenóis/classificação , Polifenóis/farmacocinética , Solubilidade , Estilbenos , Taninos
4.
AAPS PharmSciTech ; 22(5): 169, 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34080086

RESUMO

Lutein has been used as a dietary supplement for the treatment of eye diseases, especially age-related macular degeneration. For oral formulations, we investigated lutein stability in artificial set-ups mimicking different physiological conditions and found that lutein was degraded over time under acidic conditions. To enhance the stability of lutein upon oral intake, we developed enteric-coated lutein solid dispersions (SD) by applying a polymer, hydroxypropyl methylcellulose acetate succinate (HPMCAS-LF), through a solvent-controlled precipitation method. The SD were characterized in crystallinity, morphology, and drug entrapment. In the dissolution profile of lutein SD, a F80 formulation showed resistance toward the acidic environment under simulated gastric conditions while exhibiting a bursting drug release under simulated intestinal conditions. Our results highlight the potential use of HPMCAS-LF as an effective matrix to enhance lutein bioavailability during oral delivery and to provide novel insights into the eye-care supplement industry, with direct benefits for the health of patients.


Assuntos
Luteína/síntese química , Luteína/farmacocinética , Metilcelulose/análogos & derivados , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão/métodos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Humanos , Metilcelulose/síntese química , Metilcelulose/farmacocinética , Polímeros/síntese química , Polímeros/farmacocinética , Solubilidade , Solventes , Difração de Raios X/métodos
5.
Molecules ; 26(10)2021 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-34065743

RESUMO

Dietary plant polyphenols are natural bioactive compounds that are increasingly attracting the attention of food scientists and nutritionists because of their nutraceutical properties. In fact, many studies have shown that polyphenol-rich diets have protective effects against most chronic diseases. However, these health benefits are strongly related to both polyphenol content and bioavailability, which in turn depend on their origin, food matrix, processing, digestion, and cellular metabolism. Although most fruits and vegetables are valuable sources of polyphenols, they are not usually consumed raw. Instead, they go through some processing steps, either industrially or domestically (e.g., cooling, heating, drying, fermentation, etc.), that affect their content, bioaccessibility, and bioavailability. This review summarizes the status of knowledge on the possible (positive or negative) effects of commonly used food-processing techniques on phenolic compound content and bioavailability in fruits and vegetables. These effects depend on the plant type and applied processing parameters (type, duration, media, and intensity). This review attempts to shed light on the importance of more comprehensive dietary guidelines that consider the recommendations of processing parameters to take full advantage of phenolic compounds toward healthier foods.


Assuntos
Manipulação de Alimentos/métodos , Polifenóis/análise , Polifenóis/farmacocinética , Disponibilidade Biológica , Suplementos Nutricionais/análise , Política Nutricional , Extratos Vegetais/análise , Extratos Vegetais/farmacocinética
6.
Food Chem ; 358: 129905, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33940288

RESUMO

In order to gain understanding of bioaccessibility of phenolic acids in food-grade barley, an investigation was conducted using four cooked whole-grain, hulless, barley varieties. An in vitro digestion model was used to mimic human upper gastrointestinal digestion. Boiling enhanced the extractability of bound phenolic acids while digestion increased the level of free phenolic acids. The high bioaccessibilities observed were likely due to the release of bound phenolic acids during cooking and digestion. The major bioaccessible phenolics were ferulic and p-coumaric acids with bioaccessibility ranging from 131 to 173% and 51-135%, respectively. Peru-35 had significantly greater bioaccessibility of ferulic acid compared to other varieties. A hydroxycinnamic acid amide not reported before in boiled barley, N1, N8- dicaffeoyl spermidine, was identified in free phenolic extracts with relatively high abundance compared to the phenolic acids. It may provide additional anti-inflammatory and antioxidant functions. These cooked whole-grain, hulless barley varieties are sources of bioaccessible phenolic acids.


Assuntos
Hordeum/química , Fenóis/farmacocinética , Disponibilidade Biológica , Canadá , Culinária , Ácidos Cumáricos/farmacocinética , Digestão , Humanos , Hidroxibenzoatos/farmacocinética , Fenóis/análise , Grãos Integrais/química
7.
Food Chem ; 358: 129888, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33933969

RESUMO

Present study aimed to prepare and identify antioxidative peptides from selenium-containing soybeans, and to investigate their bioavailability and protective effects against oxidative stress-related diseases. Selenium-containing soybean antioxidative peptides (Mw < 1 kDa, SePPs) hydrolyzed by Neutrase and Alcalase reached the highest cellular antioxidant activity (EC50 value 320.5 ± 39.71 µg/L). SePPs could be efficiently absorbed through Caco-2 monolayer, and then significantly reverse the tumor necrosis factor-α (TNF-α)-induced inflammatory cytokine, phosphorylated c-Jun N-terminal kinases (p-JNK) and nuclear factor-kappa B (NF-κB) levels in EA. hy926 cells (p < 0.05). d-galactose-induced aging mice model showed that liver superoxidase dismutase (SOD) and glutathione peroxidase-1 (GPx-1) were enhanced, while aspartate aminotransferase (AST), alanine aminotransferase (ALT) and NF-κB were decreased by SePPs significantly (p < 0.05). SePPs could inhibit brain oxidative stress via regulating MAPK/NF-κB pathway. Comparing with Na2SeO3, selenomethionine (SeMet) and selenium-free peptides, SePPs was found to present synergistic effects of selenium and peptides in antioxidant activity.


Assuntos
Antioxidantes/farmacologia , Peptídeos/farmacologia , Selênio/farmacologia , Proteínas de Soja/farmacologia , Animais , Antioxidantes/química , Antioxidantes/farmacocinética , Disponibilidade Biológica , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Células CACO-2 , Citocinas/metabolismo , Suplementos Nutricionais , Enzimas/metabolismo , Feminino , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos Endogâmicos ICR , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peptídeos/química , Selênio/química , Selênio/farmacocinética , Proteínas de Soja/química , Fator de Necrose Tumoral alfa/metabolismo
8.
Food Funct ; 12(9): 3883-3897, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33978004

RESUMO

We systematically investigated the impact of oil droplet diameter (≈0.15, 1.6, and 11 µm) on the bioaccessibility of three oil-soluble vitamins (vitamin A palmitate, vitamin D, and vitamin E acetate) encapsulated within soybean oil-in-water emulsions stabilized by quillaja saponin. Lipid digestion kinetics decreased with increasing droplet size due to the reduction in oil-water interfacial area. Vitamin bioaccessibility decreased with increasing droplet size from 0.15 to 11 µm: 87 to 39% for vitamin A; 76 to 44% for vitamin D; 77 to 21% for vitamin E. Vitamin bioaccessibility also decreased as their hydrophobicity and molecular weight increased, probably because their tendency to remain inside the oil droplets and/or be poorly solubilized by the mixed micelles increased. Hydrolysis of the esterified vitamins also occurred under gastrointestinal conditions: vitamin A palmitate (∼90%) and vitamin E acetate (∼3%). Consequently, the composition and structure of emulsion-based delivery systems should be carefully designed when creating vitamin-fortified functional food products.


Assuntos
Diterpenos/farmacocinética , Trato Gastrointestinal/fisiologia , Ésteres de Retinil/farmacocinética , Vitamina D/farmacocinética , Vitamina E/farmacocinética , Disponibilidade Biológica , Cápsulas , Digestão , Diterpenos/química , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Emulsões , Interações Hidrofóbicas e Hidrofílicas , Técnicas In Vitro , Metabolismo dos Lipídeos , Micelas , Tamanho da Partícula , Ésteres de Retinil/química , Solubilidade , Óleo de Soja/química , Vitamina D/química , Vitamina E/química
9.
J Anim Sci ; 99(6)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33956968

RESUMO

Two nitrogen balance studies were conducted to evaluate the relative bioavailability values (RBV) of dl-methionine (dl-Met) and dl-methionine hydroxy analog calcium salt (MHA-Ca) to l-methionine (l-Met) as Met sources fed to pigs. In experiment 1, 42 pigs were assigned to 7 treatments feeding with basal diet (BD) formulated to be deficient in Met (0.22% standardized ileal digestible basis) but adequate in other amino acids. Diets included (1) BD, (2) BD + 0.025% dl-Met, (3) BD + 0.050% dl-Met, (4) BD + 0.075% dl-Met, (5) BD + 0.025% l-Met, (6) BD + 0.050% l-Met, and (7) BD + 0.075% l-Met. Increasing levels of l-Met and dl-Met enhanced N retained (g/d) and N retention (% of intake) linearly (P < 0.01). Using a linear slope ratio procedure, a product-to-product RBV of dl-Met compared with l-Met was 94% (95% confidence limits: 65% to 123%) based on N retained expressed as g/d and 99% (95% confidence limits: 70% to 128%) for N retention expressed as % of intake. In experiment 2, 42 pigs were allotted to 7 treatments in another N-balance trial. Diets included (1) BD, (2) BD + 0.025% l-Met, (3) BD + 0.050% l-Met, (4) BD + 0.075% l-Met, (5) BD + 0.030% MHA-Ca, (6) BD + 0.060% MHA-Ca, and (7) BD + 0.089% MHA-Ca. An increase in dietary inclusion rates of l-Met increased (P < 0.01) N retained (g/d) linearly while increasing levels of MHA-Ca had no effects (P > 0.05) on N retained (g/d) and N retention (% of intake). Using linear slope-ratio regression, the RBV of MHA-Ca compared with l-Met was 70% (95% confidence limits: 59% to 81%) on a product-to-product basis or 83% on equimolar basis based on N retained expressed as g/d. Overall, the mean RBV of dl-Met to l-Met of 97% (95% confidence limits cover 100%) indicated that dl-Met and l-Met are equally bioavailable as Met sources in pigs. Compared with l-Met, the RBV of MHA-Ca was lower at 70% (95% confidence limits: 59% to 81%) on a product-to-product basis or 83% on equimolar basis in starter pigs.


Assuntos
Ração Animal , Cálcio , Ração Animal/análise , Animais , Disponibilidade Biológica , Dieta/veterinária , Suplementos Nutricionais , Metionina/análogos & derivados , Metionina/metabolismo , Nitrogênio , Suínos
10.
J Nanosci Nanotechnol ; 21(11): 5429-5435, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-33980352

RESUMO

This study investigated icariin (ICA) nanoparticles on angiogenesis in rats with pulmonary fibrosis and its mechanism. First, icariin solid nanoliposomes (ICA-SLN) were prepared. The in vitrorelease of icariin nanoparticles was determined using a UV-Vis spectrophotometer, after which the plasma concentration of icariin nanoparticles in rats was determined. The bioavailability of icariin nanoparticles was investigated, and the effect of icariin on angiogenesis of pulmonary fibrosis rats was re-observed. The results showed that the bioavailability of icariin in vivo was enhanced after nanomodification, which indicated that icariin solid nanoliposome was a good choice for oral sustained-release nanocarrier materials. in vivo experiments showed that icariin could significantly inhibit angiogenesis in rats with pulmonary fibrosis, and the inhibitory effect was related to the dose and time of action. Most importantly, this study provides the possibility of icariin as a targeted agent for future-targeted therapy.


Assuntos
Nanopartículas , Fibrose Pulmonar , Animais , Disponibilidade Biológica , Flavonoides/farmacologia , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Ratos
11.
Analyst ; 146(12): 3858-3870, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34047317

RESUMO

This article reports on the first attempt towards investigating the leaching rates in the human gastrointestinal (GI) tract of plastic-borne contaminants that can be ingested accidentally using physiologically relevant body fluids. Oral bioaccessibility under fasted and fed states was determined in dynamic mode exploiting an automatic flow setup. The flow system is able to mimic the fast uptake of the released species from the polymeric matrix by absorption in the human digestive system by the in-line removal of the leached species. Complex GI extractants based on the Unified Bioaccessibility Method (UBM, fasted state) and Versantvoort test (fed-state) were brought through a microplastic-loaded metal microcolumn for semi-continuous leaching of plasticizers (phthalic acid ester congeners) and monomer/antioxidant species (bisphenol A, BPA) followed by in-line solid-phase extraction and clean-up of GI extracts prior to liquid chromatography analysis. The temporal extraction profiles were fitted to a first-order kinetic model for the estimation of maximum bioaccessibility pools and apparent leaching rates. Among all studied contaminants, only BPA, dimethylphthalate and diethylphthalate were appreciably released under dynamic GI conditions from high-density polyethylene pellets (average size of 110 µm), with average bioaccessibility values spanning from 51 to 84% and 48 to 87% for UBM and Versantvoort methods, respectively. No statistically significant differences in oral bioaccessibility pools were found under fed- and fasted-state dynamic extractions. The apparent kinetic constants under the fed state were greater by ≥30% as a consequence of the effect of the larger amounts of bile salts and digestive enzymes in the Versantvoort test on the leaching rates. The estimated average daily intake, in which bioaccessibility data are contemplated, indicated that plastic materials exceeding 0.3% (w/w) BPA might pose real risks to human health.


Assuntos
Disruptores Endócrinos , Poluentes do Solo , Disponibilidade Biológica , Humanos , Cinética , Microplásticos , Plásticos , Poluentes do Solo/análise , Extração em Fase Sólida
12.
Environ Res ; 198: 111198, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33933486

RESUMO

Rice consumption is a major dietary source of human exposure to arsenic (As), with As bioavailability being an important factor influencing its health risk. In this study, the As bioaccessibility was measured in 11 rice grains (140-335 µg As kg-1), which were compared to As relative bioavailability previously measured based on a mouse bioassay (Li et al., 2017). Using modified physiologically-based extraction test for rice (MPBET), As bioaccessibility in raw rice samples (44-88% in the gastric phase and 47-102% in the intestinal phase) was similar to those in cooked rice (42-73% and 43-99%). Arsenic bioaccessibility in rice was generally higher in the intestinal phase than in the gastric phase, with Fe and Ca concentrations in rice being negatively correlated with As bioaccessibility in the gastric phase (R2 = 0.47-0.49). In addition, for cooked rice, strong positive correlation was observed between bioaccessible As and inorganic As (R2 = 0.63-0.72), suggesting inorganic As in rice was easier to dissolve than organic As in gastrointestinal digestive fluids. Due to limited variation in As bioaccessibility and As bioavailability among the 11 samples, a weak correlation was observed between them (R2 = 0.01-0.03); however, As bioaccessibility values measured by the gastric phase (GP) of the MPBET agreed with As bioavailability values based on a mouse bioassay, suggesting the potential of the MPBETGP to predict As bioavailability in rice. Future work is needed to ascertain the robustness of the MPBETGP in predicting As bioavailability in rice using additional samples.


Assuntos
Arsênio , Oryza , Poluentes do Solo , Arsênio/análise , Disponibilidade Biológica , Culinária , Minerais
13.
J Agric Food Chem ; 69(21): 5907-5916, 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34008400

RESUMO

This study examined the effects of a combination of soybean fiber and α-glycosyl-isoquercitrin (AGIQ) on improving quercetin bioavailability and glucose metabolism in rats fed an obesogenic diet. For 9 weeks, rats were individually fed a control diet, a high-fat high-sucrose (H) diet, H with soybean fiber (HS), or with AGIQ (HQ), or with both (HSQ). Quercetin derivatives in plasma, feces, urine, and cecal content were quantified by high-performance liquid chromatography to assess the bioavailability of quercetin, and meal tolerance tests were performed to assess postprandial glycemia and glucagon-like peptide-1 (GLP-1) responses. The HSQ group had higher plasma quercetin levels than HQ. The postprandial glycemia was attenuated in the HSQ group when compared to the H group. The basal plasma GLP-1 concentrations positively correlated with plasma quercetin derivative concentrations. Hence, the combination of soybean fiber and AGIQ could be beneficial for reducing the risk of glucose intolerance, possibly involving enhanced quercetin bioavailability and GLP-1 secretion.


Assuntos
Peptídeo 1 Semelhante ao Glucagon , Quercetina , Animais , Disponibilidade Biológica , Glicemia , Dieta Hiperlipídica/efeitos adversos , Homeostase , Insulina , Quercetina/análogos & derivados , Ratos , Soja , Sacarose
14.
Braz J Med Biol Res ; 54(8): e11073, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34037098

RESUMO

The study evaluated the effect of the supernatant of placental explants from preeclamptic (PE) and normotensive (NT) pregnant women after tissue treatment with or without vitamin D (VD) on oxidative stress and nitric oxide (NO) bioavailability in human umbilical vein endothelial cells (HUVEC). Placental explants were prepared from eight NT and eight PE women, and supernatants were obtained after incubation with or without hydrogen peroxide (H2O2) and/or VD. HUVEC were cultured for 24 h with supernatants, and the following parameters were analyzed in HUVEC cultures: NO, nitrate (NO3-), and nitrite (NO2-) levels, lipid peroxidation, and intracellular reactive oxygen species (ROS). Results showed that the production of NO3-, NO2-, malondialdehyde (MDA), and ROS were significantly higher in HUVEC treated with explant supernatant from PE compared to NT pregnant women, while the supernatant of PE explants treated with VD led to a decrease in these parameters. A significantly high production of NO was detected in HUVEC cultured with control supernatant of NT group, and in cultures treated with supernatant of PE explants treated with VD. Taken together, these results demonstrated that cultures of placental explants from PE women with VD treatment generated a supernatant that decreased oxidative stress and increased the bioavailability of NO in endothelial cells.


Assuntos
Óxido Nítrico , Pré-Eclâmpsia , Disponibilidade Biológica , Células Cultivadas , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Peróxido de Hidrogênio , Óxido Nítrico/metabolismo , Estresse Oxidativo , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Gravidez , Vitamina D/metabolismo
15.
J Med Chem ; 64(9): 6179-6197, 2021 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-33938746

RESUMO

Overexpression of ATP binding cassette (ABC) transporters, including P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), is an important factor leading to multidrug resistance (MDR) in cancer treatments. Three subclasses of dual inhibitors of P-gp and BCRP were designed based on the active moieties of BCRP inhibitors, tyrosine kinase inhibitors, and P-gp inhibitors, of which compound 21 possessed low cytotoxicity, high reversal potency, and good lipid distribution coefficient. 21 also increased the accumulation of Adriamycin (ADM) and Mitoxantrone (MX), blocked Rh123 efflux, and made no change in the protein expression of P-gp and BCRP. Importantly, coadministration of 21 can significantly improve the oral bioavailability of paclitaxel (PTX). It was also demonstrated that 21 significantly inhibited the growth of K562/A02 xenograft tumors by increasing the sensitivity of ADM in vivo. In summary, 21 has the potential to overcome MDR caused by P-gp and BCRP and to improve the oral bioavailability of PTX.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Benzeno/química , Benzeno/farmacologia , Desenho de Fármacos , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Proteínas de Neoplasias/metabolismo , Pirimidinas/química , Administração Oral , Animais , Benzeno/administração & dosagem , Disponibilidade Biológica , Interações Medicamentosas , Humanos , Células K562 , Camundongos , Paclitaxel/farmacocinética , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Mater Sci Eng C Mater Biol Appl ; 124: 112059, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33947553

RESUMO

Solid dispersion with Pluronic F127 was proposed as alternative approach to modify the pharmacologically relevant properties of methotrexate (MTX). Solid dispersion of MTX with Pluronic F127 was prepared by fusion method and characterized by powder X-ray diffraction, thermal analysis, scanning electron microscopy and FTIR spectroscopy with the aim to elucidate the physical state of the dispersed MTX and the nature of the interactions occurring between MTX and the carrier. Effect of Pluronic F127 on solubility, dissolution rate, membrane permeability, and pharmacokinetic parameters was revealed in vitro and in vivo. It was found that physical interactions of MTX with Pluronic F127 are predominant in the solid dispersion. The effect of Pluronic F127 on the MTX solubility and release rate of MTX from the solid dispersion is pH dependent. Apparent solubility of MTX released from the solid dispersion is increased in the acidic medium and remains unchanged in the alkaline medium. In comparison with the pristine MTX, the release of MTX from the solid dispersion is faster in the acidic medium and slower in the alkaline medium. Influence of Pluronic F127 on the membrane permeability of MTX is insignificant. Bioavailability of orally administrated solid dispersion in increased. Results from in vitro and in vivo studies suggested that the pharmacokinetic properties of MTX can be improved by solid dispersion with Pluronic F127.


Assuntos
Metotrexato , Poloxâmero , Disponibilidade Biológica , Portadores de Fármacos , Metotrexato/farmacologia , Solubilidade
17.
Xenobiotica ; 51(7): 811-817, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33949288

RESUMO

Esculetin is the main active ingredient isolated from Artemisia montana (Nakai) Pamp. and Euphorbia lathyris L. The present study investigated the oral bioavailability and pharmacokinetics of esculetin in rats, following intravenous and oral administration.Twenty Sprague-Dawley rats were randomly assigned to receive 10 mg/kg of esculetin either by the intravenous or oral route. Plasma concentrations of esculetin were measured using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated using non-compartmental analysis as well as a compartmental modelling approach using WinNonlinTM and ADAPT 5 software, respectively.According to non-compartmental analysis, the mean oral bioavailability of esculetin was 19%. Mean ± standard deviation values of esculetin half-life, steady-state volume of distribution and clearance, following intravenous dosing, were 2.08 ± 0.46 h, 1.81 ± 0.52 L/kg and 1.27 ± 0.26 L/h/kg, respectively. As indicated by compartmental modelling, a two-compartment pharmacokinetic model with first-order absorption and elimination rate constants of 0.98 ± 0.18 h-1 and 2.47 ± 0.28 h-1, respectively, sufficiently described the plasma concentration-time curve of esculetin.Improving our understanding of the pharmacokinetic properties of esculetin could help with future development of herbal medicine products with appropriate bioactivity.


Assuntos
Disponibilidade Biológica , Administração Intravenosa , Administração Oral , Animais , Meia-Vida , Injeções Intravenosas , Ratos , Ratos Sprague-Dawley , Umbeliferonas
18.
Xenobiotica ; 51(7): 831-841, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33952035

RESUMO

Phenolic benzotriazoles are ultraviolet-light absorbers used in a variety of industrial and consumer applications. We investigated the toxicokinetic behaviour of 9 compounds, covering unsubstituted, monosubstituted, disubstituted, and trisubstituted compounds, following a single gavage (30 and 300 mg/kg) and intravenous (IV) (2.25 mg/kg) administration in male rats.Following IV administration, no distinct pattern in plasma elimination was observed for the compounds with half-lives ranging from 15.4-84.8 h. Systemic exposure parameters, maximum concentration (Cmax) and area under the concentration time curve (AUC), generally increased with the degree of substitution.Following gavage administration, Cmax and AUC of unsubstituted compound were lower compared to the substituted compounds. Cmax and AUC increased ≤7-fold with a 10-fold increase in the dose except for the AUC of the unsubstituted compound where the increase was 30-fold. Plasma elimination half-lives for the class ranged from 1.57 to 192 h with the exception of 30 mg/kg drometrizole.Oral bioavailability was low with ∼ 6% estimated for unsubstituted compound and 12.8-23% for others at 30 mg/kg dose. Bioavailability was lower following administration of the higher dose.Taken collectively, these data point to low oral absorption of phenolic benzotriazoles. The absorption decreased with increasing dose. Substituted compounds may be less metabolized compared to the unsubstituted.


Assuntos
Fenóis , Administração Intravenosa , Administração Oral , Animais , Área Sob a Curva , Disponibilidade Biológica , Meia-Vida , Masculino , Fenóis/toxicidade , Ratos , Toxicocinética , Triazóis
19.
J Agric Food Chem ; 69(22): 6200-6213, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34044544

RESUMO

Blueberry anthocyanins are well known for their beneficial biological activities. However, the poor bioavailability of anthocyanins limits their functional capacity in vivo. Our current study aimed to detect the effects of α-casein on the absorption of blueberry anthocyanins and their metabolites in rats. Blueberry anthocyanins with and without α-casein were intragastrically administered to two groups of rats and their blood samples were collected within 24 h. Results illustrated that rapid absorption of anthocyanins was observed in the rat plasma, but their concentration was relatively low. With the complexation of α-casein, the maximum concentration (Cmax) of bioavailable anthocyanins and metabolites could increase by 1.5-10.1 times (P < 0.05 or P < 0.01). The promotional effect on the plasma absorption of malvidin-3-O-galactoside and vanillic acid was outstanding with the Cmax increasing from 0.032 to 0.323 and from 0.360 to 1.902 µg/mL, respectively (P < 0.01). Besides, the molecular docking models presented that anthocyanins could enter the structural cavity and interact with amino acid residues of α-casein, which was in accordance with the improved bioavailability of anthocyanins. Therefore, α-casein could assist more blueberry anthocyanins and their metabolites to enter blood circulation.


Assuntos
Mirtilos Azuis (Planta) , Animais , Antocianinas/metabolismo , Disponibilidade Biológica , Mirtilos Azuis (Planta)/metabolismo , Caseínas , Simulação de Acoplamento Molecular , Ratos
20.
BMC Plant Biol ; 21(1): 212, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33975563

RESUMO

BACKGROUND: Anemia is thought to affect up to 1.6 billion people worldwide. One of the major contributors to low iron (Fe) absorption is a higher proportion of cereals compared to meats and pulse crops in people's diets. This has now become a problem in both the developed and developing world, as a result of both modern food choice and food availability. Bread wheat accounts for 20 % of the calories consumed by humans and is an important source of protein, vitamins and minerals meaning it could be a major vehicle for bringing more bioavailable Fe into the diet. RESULTS: To investigate whether breeding for higher concentrations of Fe in wheat grains could help increase Fe absorption, a multiparent advanced generation intercross (MAGIC) population, encompassing more than 80 % of UK wheat polymorphism, was grown over two seasons in the UK. The population was phenotyped for both Fe concentration and Fe bioavailability using an established Caco-2 cell bioassay. It was found that increasing Fe concentrations in the grains was not correlated with higher Fe bioavailability and that the underlying genetic regions controlling grain Fe concentrations do not co-localise with increased Fe absorption. Furthermore, we show that phytate concentrations do not correlate with Fe bioavailability in our wheat population and thus phytate-binding is insufficient to explain the lack of correlation between Fe bioavailability and Fe concentrations in the wheat grain. Finally, we observed no (Fe bioavailability) or low (Fe concentration) correlation between years for these traits, confirming that both are under strong environmental influence. CONCLUSIONS: This suggests that breeders will have to select not only for Fe concentrations directly in grains, but also increased bioavailability. However the use of numerous controls and replicated trials limits the practicality of adoption of screening by Caco-2 cells by many breeders.


Assuntos
Disponibilidade Biológica , Grão Comestível/química , Ferro na Dieta/análise , Ferro na Dieta/metabolismo , Triticum/química , Triticum/genética , Triticum/metabolismo , Produtos Agrícolas/química , Produtos Agrícolas/genética , Produtos Agrícolas/metabolismo , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Variação Genética , Genótipo , Melhoramento Vegetal , Reino Unido
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