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1.
Life Sci ; 244: 117324, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31958420

RESUMO

AIMS: The aim of the present study was to evaluate the possible antioxidant role of oleic acid (OA) against Cd-induced injuries in the heart and liver tissues of male Wistar rats. MAIN METHODS: Rats were treated with either vehicle (control), or OA (10 mg/kg b.w., fed orally), or Cd (0.44 mg/kg b.w., s.c.), or both (OA + Cd) for 15 days. Following completion of the treatment period, biomarkers of organ damage and oxidative stress including ROS, activities of antioxidant enzymes and their level, activities of Krebs cycle enzymes and respiratory chain enzymes were measured. Levels of interleukins (IL-1ß, IL-6, IL-10), tumor necrosis factor (TNF-α) and nuclear factor kappa B (NFκB) were estimated to evaluate the state of inflammation. In addition, changes in mitochondrial membrane potential and status of cytochrome c (Cyt c) were also studied. KEY FINDINGS: Pre-treatment of rats with OA significantly protected against Cd-induced detrimental changes possibly by decreasing endogenous ROS through regulation of antioxidant defense system, inflammatory responses and activities of metabolic enzymes. Moreover, OA was also found to restore mitochondrial membrane potential possibly by regulating Cyt c leakage thereby increasing mitochondrial viability. SIGNIFICANCE: Our results for the first time demonstrated systematically that OA provided protection against Cd-induced oxidative stress mediated injuries in rat heart and liver tissues through its antioxidant mechanism. The results raise the possibility of using OA singly or in combination with other antioxidants or diet in the treatment of situations arising due to oxidative stress and may have future therapeutic relevance.


Assuntos
Ácido Oleico/metabolismo , Ácido Oleico/farmacologia , Animais , Antioxidantes/farmacologia , Biomarcadores/metabolismo , Cádmio/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Coração/efeitos dos fármacos , Traumatismos Cardíacos/prevenção & controle , Inflamação/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar
2.
Meat Sci ; 159: 107933, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31487571

RESUMO

The aim of this study was to research the effect of the genetic background (Retinto, Torbiscal, and their reciprocal crosses) on the subcutaneous fatty acids and the sensory characteristics of dry-cured shoulders from Iberian pig, and also to investigate whether there is some interaction between genotype and diet composition when pigs are reared indoors, to obtain information to improve the selection strategies for purebred Iberian pig. The genetic background affected both the fatty acid composition (C17:0, C17:1 n-7, C18:3 n-3 and C20:0 were significantly different) and the sensory characteristics (marbling, lean fibrousness, and flavour intensity and persistence were significantly influenced), which indicates that they should be taken into account in the selection strategies for purebred Iberian pig. In a similar way, the genotype × diet composition interaction also should be taken into account when selecting a genetic line or cross to be fed indoors on a particular diet because of its repercussion on the sensory characteristics.


Assuntos
Ração Animal/análise , Dieta/veterinária , Ácido Oleico/farmacologia , /normas , Fenômenos Fisiológicos da Nutrição Animal , Animais , Ácidos Graxos , Genótipo , Masculino , Ácido Oleico/administração & dosagem , Sensação , Suínos/genética , Suínos/fisiologia
3.
Artigo em Inglês | MEDLINE | ID: mdl-31846691

RESUMO

Glycogen synthase kinase-3ß (GSK-3ß) plays a crucial role in regulating lipid metabolism, endoplasmic reticulum (ER) stress and apoptosis in mammals, however, its gene structure and function is little known about in fish. Here, its two paralogs, grass carp (Ctenopharyngodon idella) GSK-3ß1 and GSK-3ß2 were isolated and characterized, encoding peptides of 421 and 457 amino acids, respectively. These two paralogs may have originated from the teleost-specific genome duplication (TSGD) event. Alignment of grass carp GSK-3ß deduced amino acid sequences with select teleost species showed that the protein is conserved. However, two paralogs of the GSK-3ß had great variation in gene structure: the GSK-3ß1 contained eleven exons while the GSK-3ß2 contained nine exons. The two paralogs were expressed in a wide range of tissues, GSK-3ß1 was most expressed in adipose tissue, GSK-3ß2 was most expressed in liver. In OA-induced adipocytes and hepatocytes, we found that GSK-3ß1 mRNA expression was significantly increased only in adipocytes, while the mRNA expression of GSK-3ß2 was dramatically increased both in adipocytes and hepatocytes. These results provide evidence that the GSK-3ß may participate in the process of lipid accumulation in OA-induced adipocytes and hepatocytes of grass carp.


Assuntos
Adipócitos/metabolismo , Carpas/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Hepatócitos/metabolismo , Ácido Oleico/farmacologia , Sintenia , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Sequência de Aminoácidos , Animais , Carpas/genética , Células Cultivadas , Clonagem Molecular , Glicogênio Sintase Quinase 3 beta/biossíntese , Glicogênio Sintase Quinase 3 beta/genética , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Filogenia , Homologia de Sequência de Aminoácidos , Distribuição Tecidual
4.
Pol J Vet Sci ; 22(4): 661-666, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31867919

RESUMO

In this study, the effects of oleic (18:1 cis-9-octadecenoic acid) and linoleic (18:2 (n-6), 9,12-octadecadienoic acid) acids added to the embryo culture media for bovine embryonic development after vitrification were investigated in cattle. Following maturation and fertilization, the oocytes were placed in Charles Rosencrans (CR1aa) culture drops containing 10, 100, 500, and 1000 µM of oleic or linoleic acids. On day 7 or 8 of the culture, the blastocysts and expanded blastocysts were vitrified and warmed to evaluate the viability and development. High doses of oleic acid (1000 µM) in the culture media increased the viability of embryos after vitrification. Similarly, linoleic acid at 1000 µM increased the viability compared to the other linoleic acid doses. It was observed that the addition of essential fatty acids improved the development of embryos. Increasing the concentration of linoleic and oleic acid concentrations in the media proportionally advanced the embryonic development and hatching capability after vitrification/ /warming. Specifically, the addition of high doses of oleic acid had dramatic effects on the embryonic development after vitrification/warming probably due to the increased lipid storage. In conclusion, the present results suggest that the ratio of unsaturated fatty acids in the culture media affects significantly the embryonic development in vitro.


Assuntos
Bovinos/embriologia , Embrião de Mamíferos/efeitos dos fármacos , Ácido Linoleico/farmacologia , Ácido Oleico/farmacologia , Preservação de Tecido/veterinária , Vitrificação , Animais , Criopreservação/veterinária , Meios de Cultura , Técnicas de Cultura Embrionária/veterinária , Desenvolvimento Embrionário
5.
Nutrients ; 11(9)2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31491982

RESUMO

Gut microbiota can influence the feeding behavior of the host, but the underlying mechanisms are unknown. Recently, caseinolytic protease B (ClpB), a disaggregation chaperon protein of Escherichia coli, was identified as a conformational mimetic of α-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide. Importantly, ClpB was necessary for E. coli to have an anorexigenic effect in mice, suggesting that it may participate in satiety signaling. To explore this further, we determined the short-term (2 h) effects of three macronutrients: protein (bovine serum albumin), carbohydrate (D-fructose) and fat (oleic acid), on the production of ClpB by E. coli and analyzed whether ClpB can stimulate the secretion of the intestinal satiety hormone, peptide YY (PYY). Isocaloric amounts of all three macronutrients added to a continuous culture of E. coli increased ClpB immunoreactivity. However, to increase the levels of ClpB mRNA and ClpB protein in bacteria and supernatants, supplementation with protein was required. A nanomolar concentration of recombinant E. coli ClpB dose-dependently stimulated PYY secretion from the primary cell cultures of rat intestinal mucosa. Total proteins extracted from E. coli but not from ClpB-deficient E. coli strains also tended to increase PYY secretion. These data support a possible link between E. coli ClpB and protein-induced satiety signaling in the gut.


Assuntos
Endopeptidase Clp/metabolismo , Escherichia coli K12/enzimologia , Proteínas de Escherichia coli/metabolismo , Comportamento Alimentar , Microbioma Gastrointestinal , Proteínas de Choque Térmico/metabolismo , Mucosa Intestinal/microbiologia , Resposta de Saciedade , Animais , Células Cultivadas , Endopeptidase Clp/genética , Escherichia coli K12/efeitos dos fármacos , Escherichia coli K12/genética , Proteínas de Escherichia coli/genética , Frutose/farmacologia , Regulação Bacteriana da Expressão Gênica , Regulação Enzimológica da Expressão Gênica , Proteínas de Choque Térmico/genética , Interações Hospedeiro-Patógeno , Mucosa Intestinal/metabolismo , Masculino , Ácido Oleico/farmacologia , Peptídeo YY/metabolismo , Ratos Sprague-Dawley , Soroalbumina Bovina/farmacologia , Transdução de Sinais
6.
Molecules ; 24(16)2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31408938

RESUMO

Resveratrol (RES) possesses anti-inflammatory and anti-oxidant activities, and it can prevent liver lipid metabolism disorders in obese and diabetic individuals. This study elucidated the mechanisms of brain and muscle Arnt-like protein-1 (Bmal1) in the protective effects of RES against liver lipid metabolism disorders. The results indicated that RES ameliorated free fatty acid (FFA)-induced (oleic acid (OA): palmitic acid (PA) = 2:1) glycolipid metabolic disorders in hepatocytes. Simultaneously, RES partially reverted the relatively shallow daily oscillations of FFA-induced circadian clock gene transcription and protein expression in HepG2 cells. RES also attenuated FFA-triggered reactive oxygen species (ROS) secretion and restored mitochondrial membrane potential consumption, as well as the restoration of mitochondrial respiratory complex expression. This study provides compelling evidence that RES controls intracellular lipid metabolic imbalance in a Bmal1-dependent manner. Overall, RES may serve as a promising natural nutraceutical for the regulation of lipid metabolic disorders relevant to the circadian clock.


Assuntos
Fatores de Transcrição ARNTL/genética , Relógios Circadianos/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Resveratrol/farmacologia , Fatores de Transcrição ARNTL/antagonistas & inibidores , Fatores de Transcrição ARNTL/metabolismo , Animais , Proteínas CLOCK/genética , Proteínas CLOCK/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Relógios Circadianos/genética , Criptocromos/genética , Criptocromos/metabolismo , Regulação da Expressão Gênica , Células Hep G2 , Hepatócitos/citologia , Hepatócitos/metabolismo , Homeostase/genética , Humanos , Metabolismo dos Lipídeos/genética , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Ácido Oleico/antagonistas & inibidores , Ácido Oleico/farmacologia , Ácido Palmítico/antagonistas & inibidores , Ácido Palmítico/farmacologia , Proteínas Circadianas Period/genética , Proteínas Circadianas Period/metabolismo , Cultura Primária de Células , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
7.
Eur J Pharmacol ; 861: 172618, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31430456

RESUMO

Pinolenic acid (PLA), a natural compound isolated from pine nut oil, has been reported to exert bioactivity against lipid anabolism. Nonetheless, the underlying mechanisms still poorly elucidated. The aim of this study is to comprehensively demonstrate the effects of PLA on oleic acid (OA)-induced non-alcoholic fatty liver disease (NAFLD) and their relationship with the lipid metabolic regulation. The results demonstrated that treatment with PLA dramatically inhibited lipid accumulation, oxidative stress as well as inflammatory responses induced by oleic acid in HepG2 cells. PLA also obviously decreased the levels of cellular triglyceride (TG), total cholesterol (TC), malondialdehyde (MDA), reactive oxygen species (ROS) and nitric oxide (NO). As well as PLA stilled promoted the antioxidant enzymes activity including superoxide dismutase (SOD) and glutathione peroxidase (GPX). Furthermore, PLA could increase the expressions of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase1 (HO-1) to alleviate oxidative damage. It also could reduce lipogenesis-related transcription factors expression, such as sterol regulatory element-binding protein 1 (SREBP1c), fatty acid synthase (FASN) and stearoyl-CoA desaturase 1 (SCD1). PLA treatment resulted in increasing phosphorylation of AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-α (PPARα) expression. However, pretreatment with compound C (inhibitor of AMPK) inhibited the effect of PLA on promoting the expression of p-AMPK, SIRT1 and PPARα for lipolysis. Taken together, these results demonstrated that PLA possessed the potential to prevent lipid accumulation in OA-induced HepG2 cells via upregulating the AMPK/SIRT1 signaling pathway, which supported the development of new drug candidate against non-alcoholic steatohepatitis.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Ácidos Linolênicos/farmacologia , Lipogênese/efeitos dos fármacos , Ácido Oleico/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Óxido Nítrico/metabolismo , PPAR alfa/metabolismo
8.
Appl Physiol Nutr Metab ; 44(8): 840-848, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31274012

RESUMO

Perilipin 5 (Plin5), a member of the PAT (Perilipin, ADRP, and Tip47) protein family, has been implicated in the regulation of cellular neutral lipid accumulation in nonalcoholic fatty liver diseases. However, the underlying regulatory mechanisms of Plin5 are not clear. The goal of the present study was to explore the mechanism of oleic acid (OA)-induced Plin5 expression in HepG2 cells. We found that the expression of Plin5 was increased during OA-induced lipid droplets formation in a dose- and time-dependent manner. During this process of OA-stimulated lipid droplets formation, peroxisome proliferator-activated receptor alpha (PPARα) was also upregulated. When PPARα activation was blocked by GW6471, OA-induced Plin5 expression and lipid droplets formation were effectively ablated. We further found that the phosphoinositide 3-kinase (PI3K) inhibitor LY294002 was able to downregulate both PPARα and Plin5 expression and lipid droplets formation. Thus, we concluded that PI3K may, at least in part, act upstream of PPARα to regulate Plin5 expression and lipid droplets formation in HepG2 cells.


Assuntos
Gotículas Lipídicas/fisiologia , Ácido Oleico/farmacologia , PPAR alfa/metabolismo , Perilipina-5/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Compostos Azo/química , Cromonas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Imidazóis/farmacologia , Morfolinas/farmacologia , Oxazóis/farmacologia , PPAR alfa/antagonistas & inibidores , PPAR alfa/genética , Perilipina-5/genética , Fosfatidilinositol 3-Quinases/genética , Piridinas/farmacologia , Coloração e Rotulagem , Sulfonas/farmacologia , Tiofenos/farmacologia , Tirosina/análogos & derivados , Tirosina/farmacologia
9.
Food Funct ; 10(7): 4381-4395, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31282516

RESUMO

In this work, fucoxanthin-oleic acid-protein complexes were constructed to improve the dispersibility and intestinal absorption of fucoxanthin in water. The in vivo absorption/antioxidant capacity was evaluated using a mouse model, and the binding processes were investigated using multi-spectroscopic methods and molecular docking. Results showed that the oleic acid-protein delivery system dramatically improved the absorption of fucoxanthin mainly in its original form. When the molar ratio of oleic acid to bovine serum albumin (BSA) was 4 : 1, the plasma response level of fucoxanthin at 4 h could reach 91.25% that of the pure soybean oil delivery system (336.9 pg mL-1vs. 369.2 pmol mL-1). Furthermore, the loading capacity of BSA to fucoxanthin was increased 5 times when oleic acid acted as a protein ligand. Fucoxanthin, oleic acid and BSA can form complexes with good water dispersibility (transmittance nearly 90% and particle size 265 nm) at the molar ratio of 5 : 4 : 1. Spectral analysis and molecular docking indicated that oleic acid and fucoxanthin have different binding domains in BSA and that fucoxanthin can bind to the hydrophobic cavity of BSA in a static manner. After administration of fucoxanthin-oleic acid-BSA complexes for 15 days in mice, only fucoxanthinol accumulation was discovered in eyes and the ocular antioxidant capability increased by 71.02%. These results suggest that the oleic acid-protein delivery system may be useful in facilitating the application of fat-soluble active substances to hydrophilic food systems.


Assuntos
Olho/efeitos dos fármacos , Absorção Intestinal/efeitos dos fármacos , Ácido Oleico/farmacologia , Água/química , Xantofilas/farmacologia , Animais , Antioxidantes , Digestão , Feminino , Tecnologia de Alimentos , Interações Hidrofóbicas e Hidrofílicas , Ligantes , Camundongos , Camundongos Endogâmicos ICR , Modelos Animais , Simulação de Acoplamento Molecular , Tamanho da Partícula , Soroalbumina Bovina/química , Óleo de Soja , Xantofilas/sangue , Xantofilas/química , beta Caroteno/análogos & derivados
10.
Growth Factors ; 37(1-2): 76-84, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31215273

RESUMO

To investigate (1) the effect of vascular endothelial growth factor B (VEGFB) on lipid accumulation and the alteration of fatty acids and fatty acid-related enzymes in C2C12 myotubes incubated with fatty acids and (2) the regulatory effect of VEGFB on skeletal muscle lipid metabolism. Mouse C2C12 myotubes were incubated with oleic acid (OA) and palmitic acid (PA), and differentiated mature C2C12 myotubes were treated with VEGFB. Oil-red O staining, BODIPY staining and cell triglycerides (TG) content were examined. Total RNA was isolated, and real-time PCR analysis was performed. Treatment with 100 µM OA and 50 µM PA induced lipid droplet accumulation and increased TG content (p < .01), and 100 ng/mL VEGFB reduced lipid droplet accumulation and decreased TG content (p < .01). Treatment with 100 ng/mL VEGFB significantly induced the mRNA expression of fatty acid transport protein 1 (FATP1) (p < .01) and FATP4 (p < .01). Treatment with 100 ng/mL VEGFB significantly induced the mRNA expression of adipose TG lipase and hormone-sensitive lipase (p < .01) as well as carnitine palmitoyltransferase I (p < .01), peroxisome proliferator-activated receptor-γ coactivator-1α (p < .01), acyl-coa dehydrogenase very long chain (p < .05), acyl-coa synthetase long-chain family member 1 (p < .01), peroxisomal acyl-coenzyme A oxidase 1 (p < .05), and mitochondrial uncoupling protein 3 (p < .01). VEGFB enhanced FATP1and FATP4 expression, promoted C2C12 myotube fatty acid oxidation and TG decomposition, and inhibited C2C12 myotube fatty acid re-esterification, thus inhibiting lipid accumulation in C2C12 myotubes incubated with fatty acids.


Assuntos
Metabolismo dos Lipídeos , Fibras Musculares Esqueléticas/metabolismo , Ácido Oleico/farmacologia , Ácido Palmítico/farmacologia , Fator B de Crescimento do Endotélio Vascular/farmacologia , Animais , Linhagem Celular , Proteínas de Transporte de Ácido Graxo/genética , Proteínas de Transporte de Ácido Graxo/metabolismo , Gotículas Lipídicas/metabolismo , Camundongos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo
11.
Planta Med ; 85(9-10): 719-728, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31137047

RESUMO

Abnormal lipid metabolism, such as increased fatty acid uptake and esterification, is associated with nonalcoholic fatty liver disease (NAFLD). The aqueous extract of the aerial part of Angelica tenuissima Nakai (ATX) inhibited high-fat diet-induced hepatic steatosis in mice as well as oleic acid-induced neutral lipid accumulation in HepG2 cells. ATX decreased the mRNA and protein levels of CD36 and diglyceride acyltransferase 2 (DGAT2), the maturation of sterol regulatory element-binding proteins (SREBP), and the expression of the lipogenic target genes fasn and scd1. The ATX components, Z-ligustilide and n-butylidenephthalide, inhibited the expression of FATP5 and DGAT2 and thus oleic acid-induced lipid accumulation in HepG2 cells. These results suggest that ATX and its active components Z-ligustilide and n-butylidenephthalide inhibit fatty acid uptake and esterification in mice and have potential as therapeutics for NAFLD.


Assuntos
4-Butirolactona/análogos & derivados , Angelica/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Anidridos Ftálicos/farmacologia , 4-Butirolactona/isolamento & purificação , 4-Butirolactona/farmacologia , Animais , Dieta Hiperlipídica/efeitos adversos , Avaliação Pré-Clínica de Medicamentos/métodos , Regulação da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Lipogênese/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ácido Oleico/farmacologia , Anidridos Ftálicos/isolamento & purificação , Componentes Aéreos da Planta/química , Extratos Vegetais/análise , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
12.
Parasitol Res ; 118(7): 2295-2304, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31093751

RESUMO

Acanthamoeba castellanii belonging to the T4 genotype is an opportunistic pathogen which is associated with blinding eye keratitis and rare but fatal central nervous system infection. A. castellanii pose serious challenges in antimicrobial chemotherapy due to its ability to convert into resistant, hardy shell-protected cyst form that leads to infection recurrence. The fatty acid composition of A. castellanii trophozoites is known to be most abundant in oleic acid which chemically is an unsaturated cis-9-Octadecanoic acid and naturally found in animal and vegetable fats and oils. This study was designed to evaluate antiacanthamoebic effects of oleic acid against trophozoites, cysts as well as parasite-mediated host cell cytotoxicity. Moreover, oleic acid-conjugated silver nanoparticles (AgNPs) were also synthesized and tested against A. castellanii. Oleic acid-AgNPs were synthesized by chemical reduction method and characterized by ultraviolet-visible spectrophotometry, atomic force microscopy, dynamic light scattering analysis, and Fourier transform infrared spectroscopy. Viability, growth inhibition, encystation, and excystation assays were performed with 10 and 5 µM concentration of oleic acid alone and oleic acid-conjugated AgNPs. Bioassays revealed that oleic acid alone and oleic acid-conjugated AgNPs exhibited significant antiamoebic properties, whereas nanoparticle conjugation further enhanced the efficacy of oleic acid. Phenotype differentiation assays also showed significant inhibition of encystation and excystation at 5 µM. Furthermore, oleic acid and oleic acid-conjugated AgNPs also inhibited amoebae-mediated host cell cytotoxicity as determined by lactate dehydrogenase release. These findings for the first time suggest that oleic acid-conjugated AgNPs exhibit antiacanthamoebic activity that hold potential for therapeutic applications against A. castellanii.


Assuntos
Ceratite por Acanthamoeba/tratamento farmacológico , Acanthamoeba castellanii/efeitos dos fármacos , Amebicidas/farmacologia , Nanopartículas Metálicas/química , Ácido Oleico/farmacologia , Ceratite por Acanthamoeba/parasitologia , Amebicidas/química , Animais , Olho/parasitologia , Humanos , Microscopia de Força Atômica , Ácido Oleico/química , Prata/química , Espectrofotometria Ultravioleta , Trofozoítos/efeitos dos fármacos
13.
Colloids Surf B Biointerfaces ; 180: 254-262, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31059983

RESUMO

Microemulsions have attracted great interest in the biomedical field involving drug delivery, skin treatment and immune-adjuvant. In any case, microemulsions administered in vivo will more or less contact blood tissue inevitably, however there is no specialized investigation on the interaction between microemulsions and human blood components at cellular and membrane levels. Herein we investigate the effect of a typical microemulsion formulation (Cremophor EL/ethanol/oleinic acid/water (CEOW-ME)) with different extent dilution on human blood components (red blood cells (RBCs), coagulation factor, plasma albumin) and blood coagulation function. It was found that CEOW-ME had a concentration dependent effect on blood components and displayed anti-coagulant activity, causing coagulation factor activation, platelet aggregation impairment and RBC morphology alteration, whereas no impacting on fibrinogen polymerization. Interestingly CEOW-ME had greater influence on the coagulation factors in the plasma related to intrinsic coagulation pathway than extrinsic coagulation pathway. Additionally, spectroscopy studies (DLS, UV-vis, Fluorescence and CD) demonstrated that the impact of CEOW-ME on the size, local micro-structure and conformation of albumin was mediated by hydrophobic binding-induced unfolding and disordering of hierarchical albumin structure. These findings give more comprehensive information for forecasting the potential interaction of the in vivo-administered microemulsions with the cells and bioactive molecules in the human blood.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Eritrócitos/fisiologia , Etanol/farmacologia , Glicerol/análogos & derivados , Ácido Oleico/farmacologia , Água/farmacologia , Difusão Dinâmica da Luz , Emulsões , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/ultraestrutura , Glicerol/farmacologia , Hemólise/efeitos dos fármacos , Humanos , Cinética , Ácido Oleico/química , Tempo de Tromboplastina Parcial , Tamanho da Partícula , Estrutura Secundária de Proteína , Tempo de Protrombina , Albumina Sérica Humana/química , Albumina Sérica Humana/metabolismo , Eletricidade Estática , Temperatura Ambiente , Tromboelastografia
14.
Indian J Pharmacol ; 51(1): 45-54, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31031467

RESUMO

OBJECTIVES: Sophorolipids (SLs) are a group of surface-active glycolipids produced by a type of nonpathogenic yeast Candida bombicola in the presence of vegetable oil through fermentation technology. SLs have shown antitumor activity; however, the mechanism of action underlying the anticancer activity of SLs is poorly understood. This work evaluated the anticancer activity of SLs fermented from palm oil by exploring its antiangiogenic activity. MATERIALS AND METHODS: The SLs that were fermented and further characterized for their biochemical activities. Cytotoxicity study was performed to assess cytostatic properties. A series of in vitro and ex vivo angiogenesis assay was also carried out. The relative fold change in the expression of p53 mRNA by SLs was also studied. RESULTS: Altogether, the data show that SLs derived from palm oil fermentation process inhibited neovascularization in the ex vivo tissue segments and also the endothelial cell proliferation between 50% and 65% inhibition as a whole. The palm oil derived SLs also caused downregulation of the suppression level of vascular endothelial growth factor and also upregulate the p53 mRNA level. The analytical studies revealed the presence of high amount of phenolic compounds but with relatively weak antioxidant activity. The gas chromatography-mass spectrometry studies revealed abundant amount of palmitic and oleic acid, the latter an established antiangiogenic agent, and the former being proangiogenic. CONCLUSION: Therefore, it can be concluded from this study that SLs derived from fermented palm oil have potent antiangiogenic activity which may be attributed by its oleic acid component.


Assuntos
Inibidores da Angiogênese/farmacologia , Candida/química , Glicolipídeos/farmacologia , Ácido Oleico/farmacologia , Óleo de Palmeira/química , Animais , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/fisiologia , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Fermentação , Humanos , Ratos , Fator A de Crescimento do Endotélio Vascular/metabolismo
15.
Trop Anim Health Prod ; 51(7): 1823-1827, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30945154

RESUMO

Zebu bulls are a shy breeder and they exhibit optimum libido in the presence of females with estrus phase. Continuous semen collection with the use of male dummy leads to lack of adequate sexual stimulation. Therefore, the present study was designed to test the effect of estrus-specific molecule(s) for effective sexual preparation of donor bulls. The bulls were divided into normal and poor libido group, five bulls in each group by taking 1-month control study data after collecting the information of individual bull's sexual behaviour during semen collection by regular semen collector. The bulls were never being exposed to female animals and semen was collected by an artificial vagina. The ten animals were exposed to a glycerol-water solution (50/50 v:v) as control and then exposed to estrus-specific molecules one by one. The estrus-specific molecules like squalene, 1-iodoundecane, acetic acid, coumarin, propionic acid, oleic acid, and 2-butanone were purchased from Sigma-Aldrich Company, USA, and the molecules were solubilised individually in a non-pressurised aerosol dispenser as 1.0% concentration in glycerol-water solution (50/50, v:v). Identical bulls were used as the control and exposed to each molecule one by one by giving a refractory period of 14 days. A nasal spray of acetic acid or 2-butanone significantly (p < 0.05) reduced reaction time (RT) and total time taken to ejaculate (TTTE) in normal libido bull group. Semen volume, sperm concentration, and the total number of sperm per ejaculation obtained did not show significant improvement in the normal libido group of bulls after the application of estrus-specific molecules as compared to the control. In poor libido group, acetic acid, oleic acid, and 2-butanone application showed significant (p < 0.01) improvement in RT and TTTE as compared to the control group, whereas semen production variables like sperm concentration and total sperm output per ejaculation increased significantly (p < 0.05) except semen volume. There was significant (p < 0.01) reduction in RT (%) and TTTE (%) after the application of acetic acid followed by 2-butanone and oleic acid. The sperm concentration and total sperm output per ejaculation were more after the application of each molecule but significant increase (p < 0.05) in sperm concentration was observed with 2-butanone (11.42%), acetic acid (11.42%), and oleic acid (10.13%), whereas total sperm output per ejaculation increased significantly (p < 0.05) only after the application of acetic acid and 2-butanone (24.75% and 26.84%). Hence, it can be concluded that acetic acid, 2-butanone, and oleic acid are effective for better sexual preparation of Sahiwal bulls and total sperm output per ejaculation.


Assuntos
Bovinos/fisiologia , Libido/fisiologia , Sêmen/fisiologia , Ácido Acético/farmacologia , Animais , Butanonas/farmacologia , Cumarínicos/farmacologia , Estro/fisiologia , Índia , Masculino , Ácido Oleico/farmacologia , Propionatos/farmacologia , Espermatogênese/efeitos dos fármacos , Esqualeno/farmacologia , Clima Tropical
16.
Mol Med Rep ; 19(6): 4673-4684, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30957185

RESUMO

Non­alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease, and has high rates of morbidity and mortality worldwide. Daphnetin (DAP) possesses notable antioxidative, anti­inflammatory and anticoagulant activities; DAP is an active ingredient extracted from Daphne Koreana Nakai. To investigate the effects and the underlying mechanism of DAP on NAFLD, we treated HepG2 cells with oleic acid (OA) and DAP simultaneously and non­simultaneously. In the simultaneous treatment condition, HepG2 cells were co­treated with 0.5 mM OA and DAP (5, 20, and 50 µM) for 24 h. In the non­simultaneous treatment conditions, HepG2 cells were pretreated with 0.5 mM OA for 24 h, and then treated with DAP (5, 20 and 50 µM) for 24 h. Following the aforementioned treatments, the biochemical indexes associated with NAFLD were measured as follows: i) The intracellular contents of triglyceride (TG), reactive oxygen species (ROS) and fluorescent glucose 2­[N­(7­nitrobenz­2­oxa­1,3­diazol­4­yl) amino]­2­deoxyglucose were analyzed with corresponding detection kits; and ii) the cellular expression levels of glycolipid metabolism­ and oxidative stress­related genes, including 5'AMP­activated protein kinase (AMPK), sterol regulatory element­binding protein­1C (SREBP­1C), patatin­like phospholipase domain­containing protein 3 (PNPLA3), peroxisome proliferator­activated receptor α (PPARα), phosphoinositide 3­kinase (PI3K), protein kinase B (AKT), nuclear factor­like 2 (Nrf2), cytochrome P450 (CYP) 2E1 and CYP4A were determined by reverse transcription­quantitative polymerase chain reaction and western blotting. The results revealed the potential mechanism underlying the effects of DAP on NAFLD in vitro: i) By increasing the phosphorylation of AMPK, DAP inhibited the expression of SREBP­1C and PNPLA3, and induced that of PPARα. Lipid accumulation within hepatocytes was reduced; ii) by upregulating PI3K expression and pAKT/AKT levels, DAP may alleviate insulin resistance and promote hepatocellular glucose uptake; and iii) by upregulating the expression of Nrf2, DAP downregulated the expression of CYP2E1 and CYP4A, and the levels of reactive oxygen species in hepatocytes.


Assuntos
Resistência à Insulina , Metabolismo dos Lipídeos/efeitos dos fármacos , Ácido Oleico/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Umbeliferonas/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Citocromo P-450 CYP2E1/genética , Citocromo P-450 CYP2E1/metabolismo , Citocromo P-450 CYP4A/genética , Citocromo P-450 CYP4A/metabolismo , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Lipase/antagonistas & inibidores , Lipase/genética , Lipase/metabolismo , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , PPAR alfa/genética , PPAR alfa/metabolismo , Fosfatidilinositol 3-Quinase/genética , Fosfatidilinositol 3-Quinase/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/antagonistas & inibidores , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Triglicerídeos/metabolismo
17.
Biosci Biotechnol Biochem ; 83(9): 1747-1755, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31017523

RESUMO

Citrus plants are rich in flavonoids and beneficial for lipid metabolism. However, the mechanism has not been fully elucidated. Both citrus peel flavonoid extracts (CPFE) and a mixture of their primary flavonoid compounds, namely, nobiletin, tangeretin and hesperidin, citrus flavonoid purity mixture (CFPM), were found to have lipid-lowering effects on oleic acid-induced lipid accumulation in HepG2 cells. The carnitine palmitoyltransferase 1α (CPT1α) gene was markedly increased, while the fatty acid synthase (FAS) gene was significantly decreased by both CPFE and CFPM in oleic acid-treated HepG2 cells. Flavonoid compounds from citrus peel suppressed miR-122 and miR-33 expression, which were induced by oleic acid. Changes in miR-122 and miR-33 expression, which subsequently affect the expression of their target mRNAs FAS and CPT1α, are most likely the principal mechanisms leading to decreased lipid accumulation in HepG2 cells. Citrus flavonoids likely regulate lipid metabolism by modulating the expression levels of miR-122 and miR-33.


Assuntos
Citrus/química , Flavonoides/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , MicroRNAs/genética , Extratos Vegetais/farmacologia , Regulação para Baixo/efeitos dos fármacos , Ácido Graxo Sintase Tipo I/genética , Células Hep G2 , Humanos , Lipogênese/genética , Ácido Oleico/farmacologia , Reação em Cadeia da Polimerase em Tempo Real , Regulação para Cima/efeitos dos fármacos
18.
Eur J Pharm Biopharm ; 139: 262-271, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30981946

RESUMO

The transdermal route offers an attractive alternative route of drug administration especially for Alzheimer's disease patients through eliminating gastrointestinal side effects and ultimately improving compliance. In this study, we prepared an optimized matrix-type patches for the transdermal delivery of galantamine free base with ex vivo and in vitro evaluation. Four pressure sensitive adhesives with different functional groups, ten penetration enhancers and four drug loadings were tested to determine the optimized patch. The ex vivo permeation of the different formulated patches through human cadaver skin using vertical Franz diffusion cells showed that GELVA GMS 788 was the best pressure sensitive adhesive among the tested polymers. FT-IR and rheological studies done to investigate any potential interactions of the polymer with the drug and/or additives showed the possibility of hydrogen bonding between the drug and pressure sensitive adhesive (PSA), also the additives had a plasticization effect causing increased flexibility of the polymer chains. The optimized formulation had 10%w/w drug loading, 5% w/w limonene as a penetration enhancer, and 5%w/w oleic acid as a crystallization inhibitor. The combination of limonene and oleic acid increased the flux of galantamine by 2.7-fold compared to 1.7-fold when limonene was used alone. The optimized patch exhibited diffusion release kinetics and fitted well to Higuchi's model and yielded a permeation rate of 32.4 ±â€¯1.41 µg/cm2/h across human cadaver skin.


Assuntos
Portadores de Fármacos/farmacologia , Galantamina/administração & dosagem , Nootrópicos/administração & dosagem , Absorção Cutânea/efeitos dos fármacos , Adesivo Transdérmico , Adesivos/química , Administração Cutânea , Idoso , Doença de Alzheimer/tratamento farmacológico , Cadáver , Cristalização , Difusão , Portadores de Fármacos/química , Avaliação Pré-Clínica de Medicamentos , Liberação Controlada de Fármacos , Feminino , Galantamina/farmacocinética , Humanos , Limoneno/química , Limoneno/farmacologia , Masculino , Adesão à Medicação , Nootrópicos/farmacocinética , Ácido Oleico/química , Ácido Oleico/farmacologia , Permeabilidade/efeitos dos fármacos , Polímeros/química , Pressão , Pele/efeitos dos fármacos , Pele/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier
19.
Skin Pharmacol Physiol ; 32(3): 132-141, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30909278

RESUMO

BACKGROUND/AIMS: The mechanisms by which permeation enhancers increase human skin permeation of caffeine and naproxen were assessed in vitro. METHODS: Active compound solubility in the vehicles and in the stratum corneum (SC), active compound flux across epidermal membranes and uptake of active and vehicle components into the SC were measured. The effect of vehicle pH on the permeation of caffeine and naproxen was also determined. RESULTS: Oleic acid and eucalyptol significantly enhanced the skin penetration of caffeine and naproxen, compared to aqueous controls. Naproxen permeation was increased from vehicles with pH presenting more ionized naproxen. Caffeine maximum flux enhancement was associated with an increase in caffeine SC solubility and skin diffusivity, whereas for naproxen a penetration enhancer/vehicle-induced increase in solubility in the SC correlated with an increase in maximum flux. SC solubility was related to experimentally determined active uptake, which was in turn predicted by vehicle uptake and active compound solubility in the vehicle. CONCLUSION: A permeation enhancer-induced alteration in diffusivity, rather than effects on SC solubility, was the main driving force behind increases in permeation flux of the hydrophilic molecule caffeine. For the more the lipophilic molecule naproxen, increased SC solubility drove the increases in permeation flux.


Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Cafeína/farmacocinética , Epiderme/efeitos dos fármacos , Naproxeno/farmacocinética , Veículos Farmacêuticos/farmacologia , Absorção Cutânea/efeitos dos fármacos , Epiderme/metabolismo , Etanol/farmacologia , Eucaliptol/farmacologia , Feminino , Humanos , Concentração de Íons de Hidrogênio , Ácido Oleico/farmacologia , Permeabilidade , Polietilenoglicóis/farmacologia , Dodecilsulfato de Sódio/farmacologia
20.
Molecules ; 24(5)2019 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-30857274

RESUMO

A series of novel caffeoylquinic acid derivatives of chlorogenic acid have been designed and synthesized. Biological evaluation indicated that several synthesized derivatives exhibited moderate to good lipid-lowering effects on oleic acid-elicited lipid accumulation in HepG2 liver cells. Particularly, derivatives 3d, 3g, 4c and 4d exhibited more potential lipid-lowering effect than the positive control simvastatin and chlorogenic acid. Further studies on the mechanism of 3d, 3g, 4c and 4d revealed that the lipid-lowering effects were related to their regulation of TG levels and merit further investigation.


Assuntos
Hipolipemiantes/síntese química , Hipolipemiantes/farmacologia , Ácido Oleico/farmacologia , Ácido Quínico/análogos & derivados , Ácido Clorogênico/farmacologia , Células Hep G2 , Humanos , Hipolipemiantes/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Ácido Quínico/síntese química , Ácido Quínico/química , Ácido Quínico/farmacologia , Sinvastatina/farmacologia
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