Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.875
Filtrar
1.
Ars pharm ; 60(4): 231-240, oct.-dic. 2019. graf, ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-188487

RESUMO

Antecedentes: durante varios años, se han realizado muchos intentos para mejorar la estabilidad liposomal. En 1986, Payne et al, introdujeron el concepto de pro-liposoma para la preparación de liposoma con el fin de evitar la inestabilidad fisicoquímica encontrada en algunas suspensiones de liposoma tales como agregación, fusión, hidrólisis, y/o oxidación. Objetivo: el objetivo de esta revisión es centrarse en diferentes aspectos relacionados con los Proliposomas, su método de preparación, técnicas de caracterización, asi como señalar su alcance en los sistemas de administración de fármacos. Métodos: los Proliposomas son una nueva forma de sistemas de administración de fármacos. Son productos granulares secos y de flujo libre compuestos por fármacos y fosfolípidos que, al añaderse el agua, se dispersan para formar una suspensión liposomal multilamelar. Resultados y discusión: estos Proliposomas son casi tan buenos o quizás mejores que los liposomas convencionales. En la presente revisión se explica brevemente el concepto de Proliposomas con un enfoque en sus componentes, preparación, caracterizaciones y su campo de aplicación. Conclusión: una extensa encuesta de literaturas y datos recogidos sugiere que los pro-liposomas son portadores de fármacos prometedores para el futuro


Background: For several years, many attempts have been made for the improvement of liposomal sta¬bility. In 1986, Payne et al, introduced the concept of Pro-liposome for liposome preparation in order to avoid physicochemical instability encountered in some liposome suspensions such as aggregation, fusion, hydrolysis, and/or oxidation. Objective: The objective of this review is to focus on different aspects related to Proliposomes, their method of preparation, characterization techniques and pointing out its scope in drug delivery systems. Methods: Proliposomes are a new form of drug delivery systems. They are dry, free-flowing granular products composed of drug and phospholipid which, upon addition of water, disperse to form a multi-lamellar liposomal suspension. Results and Discussion: These Proliposomes are nearly as good as or perhaps better than conventional liposomes. In the present review attempt has been made to briefly explain the concept of Proliposomes with a focus on its components, preparation, characterizations and their field of application. Conclusion: Extensive survey of literatures and collected data suggests that Pro-liposomes are promising drug carriers for the future


Assuntos
Lipossomos/farmacologia , Lipossomos/administração & dosagem , Fosfolipídeos/farmacologia , Disponibilidade Biológica , Lipossomos/farmacocinética , Solventes/farmacocinética , Esteroides
2.
BMC Complement Altern Med ; 19(1): 334, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31771651

RESUMO

BACKGROUND: Psoriasis, a recurrent, chronic inflammatory disorder of skin, is a common problem in middle age and elderly people. Thymoquinone (TQ), a lipid soluble benzoquinone is the major active ingredient of volatile oil of Nigella sativa (NS), possesses good anti-psoriatic activity. However, its hydrophobicity, poor aqueous solubility, and photosensitive nature obstructs its development. Therefore, in the present research work, ethosomal vesicles (EVs) loaded with TQ were assessed for its anti-psoriatic potential employing mouse-tail model. METHODS: TQ-loaded EVs were prepared by cold method, and characterized for various essential attributes, viz. particle size, morphology, percent drug entrapment, flexibility, rheological and textural analysis, and skin absorption. The optimized formulation was finally evaluated for anti-psoriatic activity on Swiss albino mice employing mouse-tail model for psoriasis. RESULTS: The spherical shaped vesicles were in the nanosize range, and had high flexibility. The EVs incorporated hydrogel was rheologically acceptable and resulted in substantial TQ retention in the skin layers. The % anti-psoriatic drug activity was observed to be substantially better in the case of TQ-loaded ethosomal gel vis-à-vis plain TQ, NS extract, and marketed formulation. CONCLUSIONS: The promising outcomes of the current studies ratify the superiority of TQ-loaded phospholipid-based vesicular systems for the management of psoriasis over other studied test formulations. This study, thus open promising avenues for topical application of TQ in the form of EV hydrogel.


Assuntos
Benzoquinonas , Portadores de Fármacos , Nanomedicina/métodos , Fosfolipídeos , Psoríase , Animais , Benzoquinonas/administração & dosagem , Benzoquinonas/química , Benzoquinonas/farmacocinética , Modelos Animais de Doenças , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Camundongos , Nigella sativa/química , Fosfolipídeos/química , Fosfolipídeos/farmacocinética , Fosfolipídeos/farmacologia , Psoríase/metabolismo , Psoríase/patologia , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologia , Absorção Cutânea/efeitos dos fármacos
3.
Mater Sci Eng C Mater Biol Appl ; 105: 110099, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31546395

RESUMO

Multi-modality strategies of albumin-mediated drug accumulation in tumor, boronate-based active tumor targeting and synergistic cancer therapy were combined together for effective treatment of breast cancer. Herein we report the development of albumin-shell oily-core nanocapsules (NCs), loaded with novel combination of hydrophobic drugs, exemestane (EXE) and hesperetin (HES), for targeted breast cancer therapy. This protein-lipid nanohybrid carrier was successfully fabricated using a simple protein-coating method based on the electrostatic adsorption of negatively charged albumin shell onto the oily core containing cationic surfactant. While EXE was directly encapsulated into the oily core, HES was pre-formulated in the form of phospholipid complex before solubilization in oily phase. In addition to albumin-mediated binding to albondin and SPARC, phenylboronic acid was chemically coupled to the albumin shell to confer additional tumor targeting. The targeted nanocarrier (TNC) demonstrated enhanced internalization into MCF-7 breast cancer cells resulting in synergistic cytotoxic activity with a combination index (CI) of 0.662 and dose reduction index (DRI) of 8.22 and 1.84 for EXE and HES, respectively. In vivo, TNC displayed superior anti-cancer activity in tumor-bearing mice compared to their non-targeted counterparts and the free drug combination. A significant reduction of both tumor volume (7-folds) and Ki67 expression (3-folds) was obtained by the targeted nanocarriers compared to positive control. Overall, the boronic-targeted albumin NCs offer a promising platform for hydrophobic drug combination against cancer therapy.


Assuntos
Androstadienos , Antineoplásicos Fitogênicos , Inibidores da Aromatase , Neoplasias da Mama , Hesperidina , Nanocápsulas , Albuminas/química , Albuminas/farmacocinética , Albuminas/farmacologia , Androstadienos/química , Androstadienos/farmacocinética , Androstadienos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/farmacologia , Inibidores da Aromatase/química , Inibidores da Aromatase/farmacocinética , Inibidores da Aromatase/farmacologia , Boro/química , Boro/farmacocinética , Boro/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Hesperidina/química , Hesperidina/farmacocinética , Hesperidina/farmacologia , Humanos , Células MCF-7 , Nanocápsulas/química , Nanocápsulas/uso terapêutico , Fosfolipídeos/química , Fosfolipídeos/farmacocinética , Fosfolipídeos/farmacologia
4.
Food Funct ; 10(7): 4177-4188, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31246210

RESUMO

Dietary eicosapentaenoic acid (EPA), a main component of fish oil, has been proved to reduce the risk of cardiovascular disease. The purpose of this study was to investigate whether the anti-atherosclerosis effect of fish oil enriched with EPA partially relied on its chemical groups at the sn-3 position. Male ApoE-/- mice were divided into three groups and were fed a high-fat diet (Model) or a high-fat diet containing EPA incorporated into phospholipids (EPA-PL) or triglycerides (EPA-TG), respectively. Compared with the model group, a decrease in the area of atherosclerosis lesions at the aorta was observed in both EPA-treated groups, in which EPA-PL was superior to EPA-TG. Notably, EPA-PL exhibited lower serum and hepatic lipid levels than the model group, whereas EPA-TG only reduced the hepatic triglyceride level. Interestingly, only EPA-PL treatment regulated the expression of genes involved in cholesterol metabolism. In addition, EPA-PL and EPA-TG suppressed the inflammation markers in the aorta and circulation. In conclusion, EPA-PL was superior to EPA-TG in reducing lesion progression by modulating the hepatic lipid metabolism, as well as decreasing the inflammation in the artery wall and circulatory system, which might be attributed to their structural differences at the sn-3 position.


Assuntos
Apolipoproteínas E/genética , Aterosclerose/tratamento farmacológico , Ácido Eicosapentaenoico/farmacologia , Fosfolipídeos/farmacologia , Triglicerídeos/sangue , Animais , Aterosclerose/metabolismo , Aterosclerose/patologia , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Óleos de Peixe/química , Regulação da Expressão Gênica , Inflamação , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipoproteínas/sangue , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
5.
J Food Sci ; 84(5): 1002-1011, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30977912

RESUMO

Although phosphatidylethanolamine (PE) is an important functional phospholipid, there have been very few reports on its antioxidant activity and corresponding molecular composition. Crude PE was extracted from egg yolk with various solvents, and response surface modeling was carried out to determine the optimum extraction conditions for PE, under which the PE content in extracts reached 58.94 µg/mL. The crude PE was purified using silica gel-based column chromatography. High-purity PE (98%), identified by high-performance liquid chromatography-evaporative light-scattering detector, was obtained using isocratic elution with a mixed solvent (chloroform: methanol: acetic acid = 18:5:1) eluent. PE purified from egg yolk exhibited high radical-scavenging activity, determined by electron paramagnetic resonance (EPR). The result was attributed to the high unsaturated fatty acids (83.10%) content in egg yolk PE, and the unsaturated fatty acids were identified as PE-16:0/18:1Δ 9 , PE-16:0/18:2Δ 9,12 , PE-16:0/20:4Δ 5,8,11,14 , PE-18:0/18:1Δ 9 , PE-18:0/18:2Δ 9,12 , and PE-18:0/20:4Δ 5,8,11,14 by MALDI-TOF MS combined with gas chromatography mass spectrometry. PRACTICAL APPLICATION: In this work, an attempt has been made to explore the antioxidant activity of PE that extracted and purified from egg yolk and its corresponding molecular composition. Owing to its plentiful unsaturated fatty acids (83.10%), purified PE from egg yolk exhibited a high radical-scavenging activity that indicated that egg-yolk PE had a strong antioxidant activity, and it might exert possible beneficial effects on the human health.


Assuntos
Antioxidantes/farmacologia , Gema de Ovo/química , Ácidos Graxos Insaturados/farmacologia , Tecnologia de Alimentos/métodos , Fosfatidiletanolaminas/farmacologia , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Cromatografia Líquida de Alta Pressão/métodos , Ácidos Graxos Insaturados/análise , Humanos , Espectrometria de Massas , Estrutura Molecular , Fosfatidiletanolaminas/química , Fosfatidiletanolaminas/isolamento & purificação , Fosfolipídeos/química , Fosfolipídeos/isolamento & purificação , Fosfolipídeos/farmacologia
6.
J Parasitol ; 105(2): 321-329, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30998130

RESUMO

The mitochondrial, inner-membrane-associated, reversible NADPH→NAD+ transhydrogenase of the energetically anaerobic adult cestode Hymenolepis diminuta connects NADPH generation, via a mitochondrial NADP+-specific "malic" enzyme, with NADH formation needed for electron transport. In reducing the pyridine nucleotide, the enzyme concomitantly catalyzes transmembrane proton translocation, thereby coupling NADH formation to ATP generation or NADPH formation to ATP hydrolysis. Detergent-solubilized transhydrogenase, from isolated mitochondrial membranes, was purified to apparent homogeneity using ion exchange and hydroxylapatite chromatographies. The enzyme displayed a monomeric Mr of ∼110 kDa and required phospholipid, without which activity was rapidly lost. Of the phospholipids examined, phosphatidylcholine was the most effective. Transhydrogenase-catalyzed NADH formation was inhibited by NAD(P)+ and adenylates, suggesting regulatory effects of the pyridine nucleotides and effects of pyridine nucleotide-simulating molecules. In keeping with its proton-translocating function, the enzyme was inhibited by dicyclohexylcarbodiimide. The isolated enzyme catalyzed neither NADH→NADP+ nor NADH→NAD+ transhydrogenations, thereby suggesting a need for a minimal coupling to electron transport for the NADH→NADP+ reaction as well as enzyme specificity. Anti-transhydrogenase monospecific antibodies proved inhibitory to NADPH→NAD+ transhydrogenation catalyzed by both isolated and membrane-associated enzymes. This purification study apparently represents a first for parasitic helminths or multicellular invertebrates generally and establishes a framework for evaluating the transhydrogenase as a potential site for specific chemotherapeutic attack.


Assuntos
Hymenolepis diminuta/enzimologia , Mitocôndrias/enzimologia , NADP Trans-Hidrogenases/isolamento & purificação , NADP/metabolismo , NAD/metabolismo , Animais , Eletroforese em Gel de Poliacrilamida , Feminino , Immunoblotting , Imunoglobulina G/imunologia , Masculino , NADP Trans-Hidrogenases/antagonistas & inibidores , NADP Trans-Hidrogenases/imunologia , NADP Trans-Hidrogenases/metabolismo , Fosfolipídeos/metabolismo , Fosfolipídeos/farmacologia , Coelhos , Ratos , Ratos Sprague-Dawley
7.
Mar Drugs ; 17(2)2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30717094

RESUMO

Global health is under attack by increasingly-frequent pandemics of viral origin. Antimicrobial peptides are a valuable tool to combat pathogenic microorganisms. Previous studies from our group have shown that the membrane-lytic region of turbot (Scophthalmus maximus) NK-lysine short peptide (Nkl71⁻100) exerts an anti-protozoal activity, probably due to membrane rupture. In addition, NK-lysine protein is highly expressed in zebrafish in response to viral infections. In this work several biophysical methods, such as vesicle aggregation, leakage and fluorescence anisotropy, are employed to investigate the interaction of Nkl71⁻100 with different glycerophospholipid vesicles. At acidic pH, Nkl71⁻100 preferably interacts with phosphatidylserine (PS), disrupts PS membranes, and allows the content leakage from vesicles. Furthermore, Nkl71⁻100 exerts strong antiviral activity against spring viremia of carp virus (SVCV) by inhibiting not only the binding of viral particles to host cells, but also the fusion of virus and cell membranes, which requires a low pH context. Such antiviral activity seems to be related to the important role that PS plays in these steps of the replication cycle of SVCV, a feature that is shared by other families of virus-comprising members with health and veterinary relevance. Consequently, Nkl71⁻100 is shown as a promising broad-spectrum antiviral candidate.


Assuntos
Antivirais/farmacologia , Linguados , Fragmentos de Peptídeos/farmacologia , Proteolipídeos/química , Proteolipídeos/farmacologia , Rhabdoviridae/efeitos dos fármacos , Internalização do Vírus/efeitos dos fármacos , Sequência de Aminoácidos , Animais , Antivirais/química , Linhagem Celular , Cyprinidae , Doenças dos Peixes/tratamento farmacológico , Doenças dos Peixes/virologia , Concentração de Íons de Hidrogênio , Fragmentos de Peptídeos/química , Fosfolipídeos/química , Fosfolipídeos/farmacologia , Rhabdoviridae/fisiologia , Viremia/tratamento farmacológico , Viremia/virologia , Replicação Viral/efeitos dos fármacos
8.
Am J Addict ; 28(2): 119-126, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30701618

RESUMO

BACKGROUND AND OBJECTIVE: Methamphetamine (MA) substance use disorder (SUD) does not have an efficacious pharmacotherapy. We developed a MA vaccine and investigated its potential to attenuate MA induced responses. METHODS: We examined a novel adjuvant, E6020, a Toll-like receptor-4 (TLR-4) agonist combined with tetanus-toxoid conjugated to succinyl-methamphetamine (TT-SMA) adsorbed on aluminum hydroxide (alum). Adult BALB/c female mice received the vaccine and booster injections at weeks 0, 3, and 6. The efficacy of the vaccine was assessed by the level and affinity of anti-MA antibodies elicited, its ability to attenuate MA induced locomotor activation and its reduction in the amount of MA entering the brains of vaccinated mice. RESULTS: The TT-SMA vaccine containing alum and E6020 adjuvant produced anti-MA antibodies with nanomolar affinities and showed threefold greater peak titer levels than without E6020 (700 vs 250 µg/ml). These antibodies significantly decreased MA-induced locomotor activation (p < .05), and reduced the brain (p < .005) MA levels following MA administration in actively immunized mice. CONCLUSIONS: Thus, this anti-MA vaccine formulated with E6020 demonstrated effective functional protection against behavioral disruptions induced by MA. SCIENTIFIC SIGNIFICANCE: Together, anti-MA vaccine showing a promising improvement in the efficacy of the vaccine that could be an effective candidate vaccine for methamphetamine use disorder (MUD). Furthermore, combinations of adjuvants may be a tool to design vaccines for MA dependence in humans. (Am J Addict 2019;XX:1-8).


Assuntos
Hidróxido de Alumínio/farmacologia , Transtornos Relacionados ao Uso de Anfetaminas/terapia , Metanfetamina/antagonistas & inibidores , Fosfolipídeos/farmacologia , Toxoide Tetânico/farmacologia , Adjuvantes Imunológicos/farmacologia , Animais , Disponibilidade Biológica , Combinação de Medicamentos , Monitoramento de Medicamentos/métodos , Camundongos , Modelos Animais , Receptor 4 Toll-Like/agonistas , Resultado do Tratamento
9.
Chem Phys Lipids ; 220: 49-56, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30796887

RESUMO

The capacity of molecules to inhibit oxidation is widely tested using liposomes as host matrices of the antioxidant molecule of interest. Spectroscopic assays are readily used for this purpose, specifically assays using 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH). In this work the effect that charged lipids have on an AAPH antioxidation assay using 4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-diaza-s-indacene-3-undecanoic acid (C11-BODIPY® 581/591) as the reporter molecule was investigated. We measured the diameter, zeta potential and spectroscopic rate of decay and area-under-the-curve (AUC) associated with liposomes containing C11-BODIPY® 581/591 at varying molar percentages (0-10 mol%) of charged (cationic or anionic) lipids and compared the results. We showed that although increasing amounts of cationic or anionic lipids did change the diameter of the liposomes, size had little to no effect on the area-under-the-curve or decay rate of fluorescence. Increased (more positive) or decreased (more negative) zeta potentials did, on the other hand, affect the spectroscopic decay rates and area-under-the-curve. The results demonstrate the importance of considering the presence of charged lipids in the AAPH antioxidation assay.


Assuntos
Amidinas/metabolismo , Antioxidantes/farmacologia , Fosfolipídeos/química , Fosfolipídeos/farmacologia , Antioxidantes/química , Lipossomos/química , Oxirredução/efeitos dos fármacos , Tamanho da Partícula
10.
J Food Sci ; 84(1): 183-191, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30633384

RESUMO

Lysophospholipids have been recognized as potent biologically active lipid mediators. However, attention has not been paid to the health benefits of dietary partial hydrolysate of phospholipids (PH-PL), which is rich in docosahexaenoic acid (DHA)-bound lysophospholipids. In this study, the effects of PH-PL on serum and liver lipid profiles of rats upon administration of PH-PL are demonstrated in comparison to those of fish oil (FO), which comprises eicosapentaenoic acid (EPA) and DHA-bound triglyceride (TG). PH-PL containing EPA and DHA was prepared via enzymatic modification of squid (Todarodes pacificus) meal that is rich in phospholipids. Male Wistar rats were fed a basal diet containing soybean oil alone (7%), FO, and PH-PL. The FO and PH-PL diets had similar EPA and DHA contents. After the rats had been fed their respective diets for 28 d, their serum and liver lipid contents, fecal lipid excretion, and hepatic gene expression level were measured. The results demonstrated that compared with the soybean oil diet alone, the PH-PL diet decreased serum and liver TG contents partially because of the enhancement of liver acyl-CoA oxidase activity and suppression of liver fatty acid synthase activity. In addition, compared with the soybean oil diet, the PH-PL group exhibited lower serum cholesterol content at least in part because of the reduction of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase mRNA expression level. We found that dietary administration of EPA and DHA containing PH-PL has a hypolipidemic effect that may help prevent the development lifestyle-related diseases.


Assuntos
Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Graxos/sangue , Fígado/efeitos dos fármacos , Lisofosfolipídeos/farmacologia , Fosfolipídeos/farmacologia , Acil-CoA Oxidase/metabolismo , Animais , Colesterol/sangue , Dieta , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/farmacologia , Óleos de Peixe/administração & dosagem , Fígado/metabolismo , Masculino , Ratos , Ratos Wistar , Óleo de Soja/administração & dosagem , Triglicerídeos/sangue
11.
Life Sci ; 219: 190-198, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30658098

RESUMO

AIMS: To initiate a state of artificial torpor we suggested a pharmacological multi-targeting strategy for simulation of the physiological pattern of natural hibernation including a significant reduction in heart rate, respiratory rate, body temperature and oxygen consumption as well as a decline in brain activity known as torpor. MATERIALS AND METHODS: We have developed a composition which initiates a pharmacologically induced torpor-like state (PITS-composition), made up of eight therapeutic agents, inert gas xenon and lipid emulsion served as a drug vehicle. KEY FINDINGS: After a single intravenous injection to rats, PITS-composition causes a rapid decline in heart rate followed by a steady decrease in body temperature from about 38.5 °C to 31.5 °C, at ambient temperature of 22 °C-23 °C. The hypothermic state may continue on average for 16-17 h with the subsequent spontaneous return of heart rate and body temperature to the initial values. In the open field test at torpor the motility, rearing and grooming were suppressed but 4-8 days later they were restored. SIGNIFICANCE: Suspended animation states, including natural hibernation or pharmacologically induced synthetic torpor are of special attention of medicine, since it may improve survival rate after cardiac arrest, brain hemorrhage and ischemia, and during long-term space traveling. The suggested here multi-targeting strategy made possible to develop the pharmacological composition able, after a single intravenous injection, to initiate long, stable and reversible hypothermia and torpor at room temperature. After the torpor, animals were able to spontaneously restore both physiological parameters, and behavioral reactions.


Assuntos
Hipotermia/induzido quimicamente , Torpor/efeitos dos fármacos , Animais , Temperatura Corporal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Difenidramina/administração & dosagem , Difenidramina/farmacologia , Combinação de Medicamentos , Frequência Cardíaca/efeitos dos fármacos , Injeções Intravenosas , Ivabradina/administração & dosagem , Ivabradina/farmacologia , Sulfato de Magnésio/administração & dosagem , Sulfato de Magnésio/farmacologia , Masculino , Consumo de Oxigênio/efeitos dos fármacos , Fenotiazinas/administração & dosagem , Fenotiazinas/farmacologia , Fosfolipídeos/administração & dosagem , Fosfolipídeos/farmacologia , Propranolol/administração & dosagem , Propranolol/farmacologia , Propiltiouracila/administração & dosagem , Propiltiouracila/farmacologia , Ratos , Ratos Wistar , Reserpina/administração & dosagem , Reserpina/farmacologia , Taxa Respiratória/efeitos dos fármacos , Serotonina/administração & dosagem , Serotonina/farmacologia , Sorbitol/administração & dosagem , Sorbitol/farmacologia , Xenônio/administração & dosagem , Xenônio/farmacologia
12.
Mar Drugs ; 17(1)2019 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-30669323

RESUMO

Marine and salmon polar lipids (PLs) extracted by conventional extractions with non-food-grade solvents (CE-salmon-PLs) possess antithrombotic bioactivities against platelet-activating factor (PAF) and thrombin. Similar effects of food-grade-extracted (FGE) marine PLs have not yet been reported. In this study, food-grade solvents were used to extract PLs from Irish organic farmed salmon (Salmo salar) fillets (FGE-salmon-PLs), while their antithrombotic bioactivities were assessed in human platelets induced by platelet aggregation agonists (PAF/thrombin). FGE-salmon-PLs were further separated by thin layer chromatography (TLC) into lipid subclasses, and the antithrombotic bioactivities of each subclass were also assessed. LC-MS was utilized to elucidate the structure-activity relationships. FGE-salmon-PLs strongly inhibited PAF-induced platelet aggregation, while their relevant anti-thrombin effects were at least three times more potent than the previously reported activities of CE-salmon-PLs. TLC-derived lipid fractions corresponding to phosphatidylcholines (PC) and phosphatidylethanolamines (PE) were the most bioactive lipid subclasses obtained, especially against thrombin. Their LC-MS analysis elucidated that they are diacyl- or alkyl-acyl- PC and PE moieties baring ω3 polyunsaturated fatty acids (PUFA) at their sn-2 position, such as eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA). Our results concerning the potent antithrombotic effects of FGE-salmon-PLs against both PAF and thrombin pathways strongly suggest that such food-grade extracts are putative candidates for the development of novel cardioprotective supplements and nutraceuticals.


Assuntos
Anticoagulantes/farmacologia , Produtos Biológicos/farmacologia , Fosfolipídeos/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Salmo salar , Animais , Anticoagulantes/química , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Voluntários Saudáveis , Humanos , Extração Líquido-Líquido/métodos , Estrutura Molecular , Fosfolipídeos/química , Fosfolipídeos/isolamento & purificação , Plasma Rico em Plaquetas/efeitos dos fármacos , Plasma Rico em Plaquetas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Solventes/química , Relação Estrutura-Atividade , Trombina/metabolismo
13.
Bioorg Chem ; 84: 51-62, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30481646

RESUMO

Two series of erlotinib-alkylphospholipid hybrids were prepared and evaluated for their antiproliferative activities against a panel of four cell lines representing lung, breast, liver and skin cancers using erlotinib and miltefosine as reference standards. Amide analogs elicited more enhanced cytotoxic activity than analogous esters. Amide derivatives 8d and 8e exhibited promising broad-spectrum antiproliferative activity and higher efficacy than reference erlotinib and miltefosine. Their cellular GI50 values was in the ranges of 24.7-46.9 µM and 26.8-43.1 µM for 8e and 8d respectively. Assay results of the inhibitory activity of the prepared compounds on EGFR kinase reaction and Akt phosphorylation in conjugation with statistical correlation analysis indicated that other mechanisms might contribute to their elicited cytotoxicities. In addition, statistical correlation analysis revealed that mechanisms of elicited cytotoxicities for amide series might be different from ester series. In addition, correlation analysis indicated variations in the mechanisms according to the types of cell line.


Assuntos
Antineoplásicos/farmacologia , Cloridrato de Erlotinib/farmacologia , Fosfolipídeos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Cloridrato de Erlotinib/química , Humanos , Estrutura Molecular , Fosfolipídeos/química , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Relação Estrutura-Atividade
14.
Anticancer Agents Med Chem ; 19(1): 66-91, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30318001

RESUMO

BACKGROUND: Alkylphospholipids (APLs) are synthetically derived from cell membrane components, which they target and thus modify cellular signalling and cause diverse effects. This study reviews the mechanism of action of anticancer, antiprotozoal, antibacterial and antiviral activities of ALPs, as well as their clinical use. METHODS: A literature search was used as the basis of this review. RESULTS: ALPs target lipid rafts and alter phospholipase D and C signalling cascades, which in turn will modulate the PI3K/Akt/mTOR and RAS/RAF/MEK/ERK pathways. By feedback coupling, the SAPK/JNK signalling chain is also affected. These changes lead to a G2/M phase cell cycle arrest and subsequently induce programmed cell death. The available knowledge on inhibition of AKT phosphorylation, mTOR phosphorylation and Raf down-regulation renders ALPs as attractive candidates for modern medical treatment, which is based on individualized diagnosis and therapy. Corresponding to their unusual profile of activities, their side effects result from cholinomimetic activity mainly and focus on the gastrointestinal tract. These aspects together with their bone marrow sparing features render APCs well suited for modern combination therapy. Although the clinical success has been limited in cancer diseases so far, the use of miltefosine against leishmaniosis is leading the way to better understanding their optimized use. CONCLUSION: Recent synthetic programs generate congeners with the increased therapeutic ratio, liposomal formulations, as well as diapeutic (or theranostic) derivatives with optimized properties. It is anticipated that these innovative modifications will pave the way for the further successful development of ALPs.


Assuntos
Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Fosfolipídeos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias/metabolismo , Neoplasias/patologia
15.
J Dairy Sci ; 102(3): 2738-2748, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30415849

RESUMO

This paper reflects the concepts reviewed during the presentation in the Joint MILK/Lactation Biology Symposium at the ADSA 2018 Annual Meeting. Our intention is to update the concepts and advances in the area of research regarding milk phospholipids or polar lipid fraction as part of a dairy ingredient used today in nutritional studies that focus on gut health as well as brain development of infants. Although processing advances have allowed the production of novel ingredients rich in milk fat globule membrane (MFGM) components, mostly monitored by phospholipid concentration and presence of membrane proteins, there is wide variability in their composition and structure. Furthermore, we aimed to include in the phospholipid fraction of milk nanovesicles designated as milk exosomes, which are secreted into milk by different secretion mechanisms than those of the fat globules but are also made up of a unique mixture of polar lipids. We consider imperative the study of polar lipid-derived structures from milk regarding composition and structure to gain insights into their biological effect in human health. Nevertheless, and tolerating the differences in composition and concentration of their components, studies supplementing the diet of infants with polar lipids (i.e., MFGM components) have shown significant advances in several areas of human health and well-being. Here we present a summary of the important components of MFGM and milk exosomes as well as an overview of the effects on gut health and brain and cognitive development when added to the diet of infants.


Assuntos
Encéfalo/crescimento & desenvolvimento , Alimentos Infantis , Intestinos/crescimento & desenvolvimento , Leite/química , Fosfolipídeos/análise , Animais , Bovinos , Exossomos , Feminino , Glicolipídeos/análise , Glicoproteínas/análise , Humanos , Lactente , Lactação , Proteínas de Membrana/metabolismo , Estado Nutricional , Fosfolipídeos/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Eur J Pharmacol ; 842: 189-196, 2019 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-30391744

RESUMO

Adhesions formation is considered a significant clinical entity implicating the healing process following major abdominal surgery, with serious clinical consequences and need for substantial health care expenditures. Several agents and substances applied either locally or systematically could potentially function as inhibitors of the formation of peritoneal adhesions endowed by limiting tissue apposition during the critical stages of mesothelial repair. Phospholipids are identified as surfactant-like substances, acting as a temporary membrane-like coverage of serosal defects. The experimental use of phospholipids for adhesions formation totals 24 publications. All retrieved studies, out of two, demonstrated the efficacy of phospholipids use in adhesions prevention. A single intraperitoneal dose of approximately 75 mg/kg of phosphatidylcholine, for a 30-min exposure time, emerges as the standard practice in terms of efficacy in both surgical alone or combined to peritonitis settings. The findings revealing an unimpeded healing of anastomoses and laparotomy wounds support the safety of this agent. The two additional properties of intraperitoneal use of phospholipids involve the inhibition of bacterial adherence/growth following impregnation of intra-abdominal drainages with phospholipids, without influencing bacterial translocation and the elimination of peritoneal carcinosis, through inhibition of intraperitoneal adhesion of tumor cells. The latter effect is achieved by a dose of phospholipids equal to 150 mg/kg. These experimental data, support that the intraperitoneal phospholipids administration can forestall adhesions formation following intra-abdominal surgical trauma, with no considerable overdosing-related adverse effects. Furthermore, these substances could possibly attenuate posttraumatic inflammation, and inhibit intraperitoneal tumor cell adhesion.


Assuntos
Fosfolipídeos/farmacologia , Complicações Pós-Operatórias/prevenção & controle , Animais , Fenômenos Biomecânicos/efeitos dos fármacos , Humanos , Fosfolipídeos/administração & dosagem , Complicações Pós-Operatórias/patologia , Aderências Teciduais/patologia , Aderências Teciduais/prevenção & controle
17.
Nutrition ; 57: 183-193, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30172995

RESUMO

OBJECTIVES: The aim of this study was to examine the stress-buffering potential of phospholipid (PL) intake on cognitive performance and neuroendocrine and psychological responses under conditions of psychosocial stress in a high-stress vulnerable (perfectionist) sample. METHODS: Fifty-four high-perfectionist men consumed a 6-wk daily intake of a bovine milk-derived PL (2.7 g/d) or placebo drink in a randomized, double-blind, placebo-controlled, parallel groups design. Working memory, executive control function, and acute physiological/subjective responses to an acute psychosocial stressor were examined before and after the 6-wk PL or placebo intake. RESULTS: PL intake improved post-stress reaction time performance on an attention-switching task (P = 0.01). No significant attenuation of the salivary cortisol stress response was shown. PL intake significantly increased mid-stress induction energetic arousal (P = 0.03). A non-significant reduction in anticipatory subjective stress was reported after PL intake (P = 0.06). Systolic and diastolic blood pressures (P<0.04 and P = 0.01, respectively) were significantly augmented in the PL condition. CONCLUSIONS: Dietary intake of bovine milk PLs conferred cognitive performance benefit under conditions of psychosocial stress but failed to moderate cortisol response. Moderation of subjective response to stress exposure may have underpinned this performance protection.


Assuntos
Pressão Sanguínea , Cognição/efeitos dos fármacos , Disfunção Cognitiva/etiologia , Hidrocortisona/sangue , Leite/química , Fosfolipídeos/farmacologia , Estresse Psicológico/complicações , Adulto , Animais , Bovinos , Disfunção Cognitiva/sangue , Disfunção Cognitiva/tratamento farmacológico , Método Duplo-Cego , Humanos , Masculino , Personalidade , Fosfolipídeos/uso terapêutico , Estresse Psicológico/sangue , Estresse Psicológico/tratamento farmacológico , Adulto Jovem
18.
J Matern Fetal Neonatal Med ; 32(19): 3226-3231, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29618229

RESUMO

Objective: To determine the plasma triglyceride (TG) and unbound free fatty acid (FFAu) levels in infants treated with increasing dosages of soybean lipid, intralipid (IL), infusion. Study design: TG and FFAu levels were measured in 78 preterm infants (BW 500-2000 g; GA 23-34 weeks) using the fluorescent probe ADIFAB2 and enzymatic method. Results: The infants' BW was 1266.2 ± 440.7 g and GA 28.8 ± 3.1 weeks. TG levels were 77.4 ± 50 mg/dL, 140.2 ± 188 mg/dL (p < .04 compared to levels during low dose IL infusion) and 135.6 ± 118 mg/dL (p < .004), respectively during increased IL rates. FFAu levels were 17.7 ± 13 nM, 47.3 ± 102.8 nM (p = .07) and 98 ± 234 nM (p = .03). TG levels correlated with IL dose, the rate of IL administration, and FFAu levels. TG and FFAu levels were higher in infants below 28 weeks' gestation Conclusions: Increasing dosage of IL is associated with increasing levels of TG and FFAu, especially in infants below 29 weeks of gestation. The increased level of FFAu suggests inefficient cellular utilization.


Assuntos
Ácidos Graxos não Esterificados/sangue , Recém-Nascido Prematuro/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos , Fosfolipídeos/farmacologia , Óleo de Soja/farmacologia , Triglicerídeos/sangue , Bilirrubina/sangue , Peso ao Nascer/efeitos dos fármacos , Peso ao Nascer/fisiologia , Emulsões/administração & dosagem , Emulsões/farmacologia , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Masculino , Nutrição Parenteral/métodos , Fosfolipídeos/administração & dosagem , Óleo de Soja/administração & dosagem , Soja/química
19.
Acta Pharmacol Sin ; 40(4): 514-521, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30002492

RESUMO

Thymopentin (TP5) is an effective immunomodulatory agent for autoimmune disease that has been used clinically for decades. However, its application is greatly limited by its extremely short half-life in vivo, poor membrane permeability and extensive metabolism in gastrointestinal tract, resulting in repeated injection and poor patient compliance. In the present study, we developed a TP5-loaded, phospholipid-based phase separation gel (PPSG) to achieve sustained drug release profile and long-lasting therapeutic effects. We firstly demonstrated the physiochemical characteristics of PPSG before and after phase transition by examining the viscosity and morphology change caused by the phase transition. Moreover, the PPSG exerted a low cytotoxicity in L929 cells and HUVECs, suggesting the biocompatibility of PPSG. A month-long drug release profile of TP5 PPSG was observed both in vitro and in vivo, revealing its sustained and controlled drug release property. Most importantly, in cyclophosphamide-induced immunosuppressive rats, a single dose of TP5 PPSG (15 mg/kg, sc) injected could normalize their T-SOD levels and CD4+/CD8+ ratio; such an immunoregulatory effect was comparable to that produced by repeated injection of TP5 solution (0.6 mg/kg per day, sc) for 14 consecutive days. Thus, TP5 PPSG has a great potential for sustained delivery of TP5 in clinical use because of its simple manufacture process, good biocompatibility and long-lasting immunomodulatory efficacy, which could greatly improve patient compliance.


Assuntos
Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Fosfolipídeos/química , Timopentina/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Ciclofosfamida , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Feminino , Géis/química , Géis/farmacologia , Humanos , Fatores Imunológicos/química , Imunossupressão , Camundongos , Fosfolipídeos/farmacologia , Ratos , Ratos Wistar , Viscosidade
20.
Cell Physiol Biochem ; 51(1): 375-392, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30453305

RESUMO

BACKGROUND/AIMS: Changes in the external mechanical field result in cytoskeleton reorganization and the formation of adaptive patterns in different types of cells, including somatic cells and sex cells. The aim of this research was to study the protein and mRNA content of cytoskeletal and sperm-specific genes in the sperm and testis cells of mice. METHODS: Mice were subjected to 30 days of antiorthostatic suspension to simulate weightlessness, followed by 12 h of recovery, while receiving essential phospholipids at a dosage of 500 mg/kg/day (30HSE and 30HSE+12h groups) or a similar dosage of a placebo (30HS and 30HS+12h groups). Accordingly, reference groups (CE group and C group) were formed. The total number and the percentage of motile spermatozoa were calculated using a Makler chamber. To analyze the number of viable spermatozoa and the permeability of their membranes, eosin staining was used as well as Diff-Quick for a morphological evaluation. Relative protein and mRNA content was estimated in a western blot and quantitative PCR assay, respectively. RESULTS: The relative protein expression levels of actin (beta and gamma) and two alpha-actinin isoforms (1 and 4) remained constant in the sperm of all study groups, except for the 30HS+12h group, where the alpha-actinin-4 level was 13% higher than in the reference group (p < 0.1). In the testis cells, the relative actin isoform content was equivalent to that in the spermatozoa. However, in the testis cells, the ACTN1 mRNA content was 17% higher in the 30HS group than in the C group (p < 0.05), and decreased after 12 h of recovery. In contrast, the ACTN4 mRNA content was 20% lower in the 30HS group than in the reference group (p < 0.05) and increased after the 12-h recovery period. At the same time, in the group administered the essential phospholipids, the relative ACTN1 and ACTN4 mRNA content did not differ from those of the reference group. The relative beta-tubulin content was similar in the reference C group and the reference CE group, which was administered the essential phospholipids. In the 30HS and 30HS+12h groups, the beta-tubulin content decreased by 19% and 22% (p < 0.05), respectively, and they also decreased in the groups administered the essential phospholipids (30HSE and 30HSE+12h groups, by 27% and 33%, respectively, p < 0.05). In the testis tissue, the relative tubulin content did not change in any of the experimental groups. At the same time, the relative mRNA content of the genes encoding the studied cytoskeletal proteins increased, which may indicate the protein content was regulated mainly at the translational level. CONCLUSION: The spermogram parameters and the content of the sperm-specific proteins and the associated mRNAs revealed a decrease in the number of mature spermatozoa in mice suspended under conditions of weightlessness. Moreover, the decrease was prevented by the administration of essential phospholipids.


Assuntos
Citoesqueleto/metabolismo , Elevação dos Membros Posteriores , Espermatozoides/metabolismo , Testículo/metabolismo , Actinas/genética , Actinas/metabolismo , Animais , Citoesqueleto/química , Proteínas de Ligação a DNA/metabolismo , Histona Desmetilases com o Domínio Jumonji/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosfolipídeos/farmacologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Motilidade Espermática , Fatores de Tempo , Tubulina (Proteína)/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA