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1.
Scand J Immunol ; 92(2): e12896, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32557749

RESUMO

Sciatic nerve injury affects quality of life. Many immune cells and inflammatory cytokines have been reported to be involved in sciatic nerve injury, but little is known about the ligands and receptors that trigger inflammatory responses. By using a modified sciatic nerve clamp injury method, we found that the recruitment of Schwann cells and the inflammatory response were enhanced after sciatic nerve injury. Toll-like receptor 4 (TLR4), one of the major members of the TLR family, is highly expressed in Schwann cells. Under certain conditions, myeloid differentiation protein 2 (MD2) binds to TLR4 on the membrane and plays important roles in the inflammatory response. The reductions in the recruitment of Schwann cells and the inflammatory response induced by the blockade of TLR4 or MD2 suggest that TLR4 and MD2 are involved in sciatic nerve injury. What are the endogenous signals that activate the inflammatory response? A large number of free saturated fatty acids (SFAs) are released from Schwann cells, adipocytes and the blood after sciatic nerve injury. Liang et al reported that Schwann cells can be stimulated by palmitic acid (PA). Here, we found that the expression and secretion of TNF-α and IL-6 were enhanced by PA treatment. Moreover, PA activated TLR4 signalling pathway-related proteins and stimulated a strong association between TLR4 and MD2. Blocking TLR4 or MD2 reversed the PA-induced inflammatory response and TLR4 downstream signalling pathway. Thus, we speculated that SFAs act as endogenous ligands that activate TLR4/MD2, thus triggering Schwann cell inflammation during sciatic nerve injury.


Assuntos
Ácidos Graxos/farmacologia , Inflamação/metabolismo , Células de Schwann/efeitos dos fármacos , Nervo Isquiático/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Ácidos Graxos/metabolismo , Masculino , Compressão Nervosa , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/lesões
2.
PLoS One ; 15(6): e0232831, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32497096

RESUMO

The burden of enteric pathogens in poultry is growing after the ban of antibiotic use in animal production. Organic acids gained attention as a possible alternative to antibiotics due to their antimicrobial activities, improved nutrient metabolism and performance. The current study was conducted to evaluate the effectiveness of organic acid blend on broilers cecal microbiota, histomorphometric measurements, and short-chain fatty acid production in Salmonella enterica serovar Typhimurium challenge model. Birds were divided into four treatments, including a negative control, positive control challenged with S. Typhimurium, group supplemented with an organic acid blend, and birds supplemented with organic acid blend and Salmonella challenged. Results illustrate significant differences in feed conversion ratios and production efficiency factor between treatment groups, however, the influence of organic acid supplement was marginal. Organic acid blend significantly increased cecal acetic and butyric acids concentrations when compared to unsupplemented groups and resulted in minor alterations of intestinal bacterial communities.


Assuntos
Acetatos/metabolismo , Ração Animal , Butiratos/metabolismo , Galinhas/microbiologia , Suplementos Nutricionais , Ácidos Graxos/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Doenças das Aves Domésticas/terapia , Salmonelose Animal/terapia , Salmonella typhimurium/efeitos dos fármacos , Animais , Ceco/microbiologia , Galinhas/metabolismo , Ácidos Graxos/administração & dosagem , Ácidos Graxos Voláteis/administração & dosagem , Ácidos Graxos Voláteis/farmacologia , Íleo/metabolismo , Íleo/ultraestrutura , Mananas/administração & dosagem , Microvilosidades/ultraestrutura , Doenças das Aves Domésticas/microbiologia , Doenças das Aves Domésticas/prevenção & controle , Distribuição Aleatória , Salmonelose Animal/microbiologia , Salmonelose Animal/prevenção & controle , Salmonella typhimurium/isolamento & purificação , Salmonella typhimurium/metabolismo
3.
PLoS One ; 15(5): e0233183, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32413078

RESUMO

Lupus is a debilitating multi-organ autoimmune disease clinically typified by periods of flare and remission. Exposing lupus-prone female NZBWF1 mice to crystalline silica (cSiO2), a known human autoimmune trigger, mimics flaring by inducing interferon-related gene (IRG) expression, inflammation, ectopic lymphoid structure (ELS) development, and autoantibody production in the lung that collectively accelerate glomerulonephritis. cSiO2-triggered flaring in this model can be prevented by supplementing mouse diet with the ω-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA). A limitation of previous studies was the use of purified diet that, although optimized for rodent health, does not reflect the high American intake of saturated fatty acid (SFA), ω-6 PUFAs, and total fat. To address this, we employed here a modified Total Western Diet (mTWD) emulating the 50th percentile U.S. macronutrient distribution to discern how DHA supplementation and/or SFA and ω-6 reduction influences cSiO2-triggered lupus flaring in female NZBWF1 mice. Six-week-old mice were fed isocaloric experimental diets for 2 wks, intranasally instilled with cSiO2 or saline vehicle weekly for 4 wks, and tissues assessed for lupus endpoints 11 wks following cSiO2 instillation. In mice fed basal mTWD, cSiO2 induced robust IRG expression, proinflammatory cytokine and chemokine elevation, leukocyte infiltration, ELS neogenesis, and autoantibody production in the lung, as well as early kidney nephritis onset compared to vehicle-treated mice fed mTWD. Consumption of mTWD containing DHA at the caloric equivalent to a human dose of 5 g/day dramatically suppressed induction of all lupus-associated endpoints. While decreasing SFA and ω-6 in mTWD modestly inhibited some disease markers, DHA addition to this diet was required for maximal protection against lupus development. Taken together, DHA supplementation at a translationally relevant dose was highly effective in preventing cSiO2-triggered lupus flaring in NZBWF1 mice, even against the background of a typical Western diet.


Assuntos
Dieta Ocidental/efeitos adversos , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-6/farmacologia , Lúpus Eritematoso Sistêmico/dietoterapia , Dióxido de Silício/toxicidade , Animais , Linfócitos B/imunologia , Citocinas/metabolismo , Suplementos Nutricionais , Modelos Animais de Doenças , Ácidos Graxos/farmacologia , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-6/metabolismo , Feminino , Glomerulonefrite/dietoterapia , Glomerulonefrite/metabolismo , Glomerulonefrite/patologia , Inflamação/imunologia , Interferon gama/metabolismo , Rim/metabolismo , Rim/patologia , Pulmão/metabolismo , Pulmão/patologia , Lúpus Eritematoso Sistêmico/induzido quimicamente , Camundongos , Linfócitos T/imunologia
5.
PLoS One ; 15(4): e0232224, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32343717

RESUMO

The Amazon region is rich in genetic resources such as oilseeds which have potentially important local commercial exploitation. Despite its high concentration of bioactive compounds, cacay (Caryodendron orinocense Karst.) oil is poorly investigated and explored. Thus, this study focuses on the physicochemical characterization (moisture, density, and saponification, iodine, and acidity values), fatty acid composition as determined by gas chromatograph mass spectrometry (GC/MS), total phenolic content (TPC), and antioxidant activity (DPPH and ABTS radical scavenging assay) of cacay oil, coconut oil and a coconut/cacay oil blend, also known as cacay butter. The antibacterial activity of cacay oil was additionally evaluated. Our study demonstrated that cacay oil presents a high amount of polyunsaturated fatty acid (PUFA) (58.3%) with an emphasis on linoleic acid and a lower acidity value (2.67 ± 0.01 cg I2/g) than butter and coconut oil, indicating a low concentration of free fatty acids. In contrast, cacay butter and coconut oil presented higher saturated fatty acid percentages (69.1% and 78.4%, respectively) and higher saponification values (242.78 and 252.22 mg KOH/g, respectively). The samples showed low moisture and relative density between 912 and 916 kg/m3. The hydrophilic fraction of cacay oil was highlighted in the quantification of TPC (326.27 ± 6.79 mg GAE/kg) and antioxidant capacity in vitro by DPPH radical scavenging assay (156.57 ± 2.25 µmol TE/g). Cacay oil inhibited the growth of Bacillus cereus (44.99 ± 7.68%), Enterococcus faecalis (27.76 ± 0.00%), and Staphylococcus aureus (11.81 ± 3.75%). At long last, this is the first study reporting the physicochemical characterization and bioactive properties of cacay butter. Coconut oil and cacay butter showed great oxidative stability potential due to higher contents of saturated fatty acids. Moreover, cacay oil presents as an alternative source of raw materials for cosmetic and biotechnology industries due to its high concentration of PUFA and for being a rich source of phenolic compounds.


Assuntos
Óleo de Coco/química , Euphorbiaceae/química , Óleos Vegetais/química , Antibacterianos/química , Antibacterianos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Fenômenos Químicos , Óleo de Coco/farmacologia , Ácidos Graxos/química , Ácidos Graxos/farmacologia , Ácidos Graxos Insaturados/química , Ácidos Graxos Insaturados/farmacologia , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/farmacologia , Testes de Sensibilidade Microbiana , Fenóis/química , Fenóis/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Óleos Vegetais/farmacologia
6.
J Nanobiotechnology ; 18(1): 43, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32164731

RESUMO

BACKGROUND: Metastasis causes the most breast cancer-related deaths in women. Here, we investigated the antitumor effect of solid lipid nanoparticles (SLN-DTX) when used in the treatment of metastatic breast tumors using 4T1-bearing BALB/c mice. RESULTS: Solid lipid nanoparticles (SLNs) were produced using the high-energy method. Compritol 888 ATO was selected as the lipid matrix, and Pluronic F127 and Span 80 as the surfactants to stabilize nanoparticle dispersion. The particles had high stability for at least 120 days. The SLNs' dispersion size was 128 nm, their polydispersity index (PDI) was 0.2, and they showed a negative zeta potential. SLNs had high docetaxel (DTX) entrapment efficiency (86%), 2% of drug loading and showed a controlled drug-release profile. The half-maximal inhibitory concentration (IC50) of SLN-DTX against 4T1 cells was more than 100 times lower than that of free DTX after 24 h treatment. In the cellular uptake test, SLN-DTX was taken into the cells significantly more than free DTX. The accumulation in the G2-M phase was significantly higher in cells treated with SLN-DTX (73.7%) than in cells treated with free DTX (23.0%), which induced subsequent apoptosis. TEM analysis revealed that SLN-DTX internalization is mediated by endocytosis, and fluorescence microscopy showed DTX induced microtubule damage. In vivo studies showed that SLN-DTX compared to free docetaxel exhibited higher antitumor efficacy by reducing tumor volume (p < 0.0001) and also prevented spontaneous lung metastasis in 4T1 tumor-bearing mice. Histological studies of lungs confirmed that treatment with SLN-DTX was able to prevent tumor. IL-6 serum levels, ki-67 and BCL-2 expression were analyzed and showed a remarkably strong reduction when used in a combined treatment. CONCLUSIONS: These results indicate that DTX-loaded SLNs may be a promising carrier to treat breast cancer and in metastasis prevention.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Docetaxel/farmacologia , Lipídeos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas/química , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Portadores de Fármacos/farmacologia , Ácidos Graxos/farmacologia , Feminino , Hexoses/farmacologia , Concentração Inibidora 50 , Camundongos , Camundongos Endogâmicos BALB C , Células NIH 3T3 , Tamanho da Partícula , Poloxâmero/farmacologia
7.
Biochim Biophys Acta Mol Basis Dis ; 1866(6): 165763, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32169502

RESUMO

Excess circulating fatty acids contribute to endothelial dysfunction that subsequently aggravates the metabolic conditions such as fatty liver diseases. However, the exact mechanism of this event is not fully understood, and the investigation on the effect of a direct exposure to fatty acids together with their subsequent fate is of interest. In this work we employed a chemically specific and label-free techniques such as Raman and CARS microscopies, to investigate the process of lipid droplets (LDs) formation in endothelial cells and hepatocytes after exposure to oleic and palmitic acid. We aimed to observe the changes in the composition of LDs associated with metabolism and degradation of lipids. We were able to characterize the diversity in the formation of LDs in endothelium as compared to hepatocytes, as well as the differences in the formation of LDs and degradation manner with respect to the used fatty acid. Thus, for the first time the spectral characteristics of LDs formed in endothelial cells after incubation with oleic and palmitic acid is presented, including the time-dependent changes in their chemical composition.


Assuntos
Hepatócitos/metabolismo , Gotículas Lipídicas/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Linhagem Celular , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Endotélio/efeitos dos fármacos , Endotélio/metabolismo , Endotélio/patologia , Ácidos Graxos/metabolismo , Ácidos Graxos/farmacologia , Hepatócitos/efeitos dos fármacos , Humanos , Gotículas Lipídicas/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Ácido Oleico/farmacologia , Ácido Palmítico/metabolismo , Ácido Palmítico/farmacologia , Análise Espectral Raman
8.
Molecules ; 25(2)2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31941074

RESUMO

This study aimed to develop nanostructured lipid carriers (NLCs) for improved oral absorption of tilmicosin (TMS) in broilers. Thus, palmitic acid, lauric acid, and stearic acid were selected as solid lipids to formulate TMS-pNLCs, TMS-lNLCs, and TMS-sNLCs, respectively. They showed similar physicochemical properties and meanwhile possessed excellent storage and gastrointestinal stability. The TMS interacted with the lipid matrix and was encapsulated efficiently in NLCs in an amorphous structure. NLCs could enhance oral absorption of TMS compared to 10% tilmicosin phosphate solution in broilers, among which the TMS-sNLCs were the most efficient drug delivery carriers, with a relative oral bioavailability of 203.55%. NLCs could inhibit the efflux of P-glycoprotein (P-pg) toward TMS, which may be involved with improved oral absorption. Taken together, these types of solid lipids influenced the enhanced level of NLCs toward oral bioavailability of TMS, and the sNLCs proved to be the most promising oral delivery carriers of TMS.


Assuntos
Portadores de Fármacos , Ácidos Graxos , Nanopartículas , Tilosina/análogos & derivados , Administração Oral , Animais , Galinhas , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Ácidos Graxos/química , Ácidos Graxos/farmacocinética , Ácidos Graxos/farmacologia , Nanopartículas/química , Nanopartículas/uso terapêutico , Tilosina/química , Tilosina/farmacocinética , Tilosina/farmacologia
9.
Molecules ; 25(2)2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31936341

RESUMO

Ultrashort cationic lipopeptides (USCLs) are promising antimicrobial agents that hypothetically may be alternatively used to combat pathogens such as bacteria and fungi. In general, USCLs consist of fatty acid chains and a few basic amino acid residues. The main shortcoming of USCLs is their relatively high cytotoxicity and hemolytic activity. This study focuses on the impact of the hydrophobic fatty acid chain, on both antimicrobial and hemolytic activities. To learn more about this region, a series of USCLs with different straight-chain fatty acids (C8, C10, C12, C14) attached to the tripeptide with two arginine residues were synthesized. The amino acid at the N-terminal position was exchanged for proteinogenic and non-proteinogenic amino acid residues (24 in total). Moreover, the branched fatty acid residues were conjugated to N-terminus of a dipeptide with two arginine residues. All USCLs had C-terminal amides. USCLs were tested against reference bacterial strains (including ESKAPE group) and Candida albicans. The hemolytic potential was tested on human erythrocytes. Hydrophobicity of the compounds was evaluated by RP-HPLC. Shortening of the fatty acid chain and simultaneous addition of amino acid residue at N-terminus were expected to result in more selective and active compounds than those of the reference lipopeptides with similar lipophilicity. Hypothetically, this approach would also be beneficial to other antimicrobial peptides where N-lipidation strategy was used to improve their biological characteristics.


Assuntos
Aminoácidos/farmacologia , Antibacterianos/farmacologia , Ácidos Graxos/farmacologia , Hemólise/efeitos dos fármacos , Lipopeptídeos/farmacologia , Cátions , Humanos , Interações Hidrofóbicas e Hidrofílicas , Lipopeptídeos/química , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade
10.
Int J Mol Sci ; 21(2)2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31936187

RESUMO

Royal jelly (RJ) is a yellowish-white and acidic secretion of hypopharyngeal and mandibular glands of nurse bees used to feed young worker larvae during the first three days and the entire life of queen bees. RJ is one of the most appreciated and valued natural product which has been mainly used in traditional medicines, health foods, and cosmetics for a long time in different parts of the world. It is also the most studied bee product, aimed at unravelling its bioactivities, such as antimicrobial, antioxidant, anti-aging, immunomodulatory, and general tonic action against laboratory animals, microbial organisms, farm animals, and clinical trials. It is commonly used to supplement various diseases, including cancer, diabetes, cardiovascular, and Alzheimer's disease. Here, we highlight the recent research advances on the main bioactive compounds of RJ, such as proteins, peptides, fatty acids, and phenolics, for a comprehensive understanding of the biochemistry, biological, and pharmaceutical responses to human health promotion and life benefits. This is potentially important to gain novel insight into the biological and pharmaceutical properties of RJ.


Assuntos
Anti-Infecciosos/química , Antioxidantes/química , Ácidos Graxos/química , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Abelhas/química , Abelhas/metabolismo , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Cosméticos , Ácidos Graxos/farmacologia , Humanos , Larva/metabolismo , Preparações Farmacêuticas/química
11.
Carbohydr Polym ; 230: 115666, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31887946

RESUMO

Amylose-fatty (C12-C16) ammonium salt inclusion complexes are effective antimicrobial polymers causing growth inhibition of microbes at concentrations as low as 40 µg/mL of the complex (2 µg/mL active cationic ligand). The complex was more effective at controlling microbes than the uncomplexed ligand. The complexes were found to be particularly effective at inhibiting the growth of fungi, yeast, gram (+) bacteria, and algae; its performance was affected by pH. The complexes were not hemolytic at concentrations up to 2000 µg/mL. These agents were determined to be surface active polymers and their antimicrobial mode of action may involve cell membrane thinning or disruption, causing moderate leakage. Increased ligand concentration provided increased antimicrobial activity. Solutions of amylose complexes were found to be stable, retaining their antimicrobial efficacy after autoclaving, or after storage at room temperature for 6 months. Antimicrobial amylose complexes were produced using readily available inexpensive materials via an easily scalable process.


Assuntos
Compostos de Amônio , Amilose , Antibacterianos , Antifúngicos , Ácidos Graxos , Nanopartículas/química , Compostos de Amônio/química , Compostos de Amônio/farmacologia , Amilose/química , Amilose/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Bactérias/efeitos dos fármacos , Ácidos Graxos/química , Ácidos Graxos/farmacologia , Fungos/efeitos dos fármacos
12.
J Anim Sci ; 98(1)2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31758795

RESUMO

An experiment was conducted to evaluate the effect of dietary medium-chain fatty acid (MCFA) addition on nursery pig growth performance, fecal microbial composition, and mitigation of porcine epidemic diarrhea virus (PEDV) following storage. A total of 360 pigs (DNA 400 × 200, Columbus, NE; initially 6.7 ± 0.07 kg) were randomized to pens (5 pigs per pen) on the day of weaning (approximately 20 d of age), allowed a 6-d acclimation, blocked by BW, and randomized to dietary treatment (9 pens per treatment). All MCFA (Sigma-Aldrich, St. Louis, MO) were guaranteed ≥98% purity, including hexanoic (C6:0), octanoic (C8:0), and decanoic (C10:0) acids. Treatment diets were formulated in 2 phases (7 to 11 and 11 to 23 kg BW) and formulated to meet or exceed NRC requirement estimates. Treatments (n = 8) were a dose response including 0%, 0.25%, 0.5%, 1.0%, and 1.5% added MCFA blend (1:1:1 ratio C6:0, C8:0, and C10:0), as well as treatments with individual additions of 0.5% C6:0, C8:0, or C10:0. Fecal samples were collected from pigs fed control and 1.5% MCFA blend diets on days 0 and 14 and analyzed using 16s rDNA sequencing. Following feed manufacture, feed was stored in bags at barn temperature and humidity for 40 d before laboratory inoculation with PEDV. Subsamples of retained feed were inoculated with PEDV to achieve a titer of 104 TCID50/g and separate sample bottles were analyzed on 0 and 3 d post-inoculation (dpi). Overall, ADG and ADFI were increased (linear, P ≤ 0.010) and feed efficiency (G:F) improved (linear, P = 0.004) with increasing MCFA blend. Pigs fed 0.5% C8:0 had greater (P = 0.038) ADG compared with pigs fed the control diet, and G:F was improved (P ≤ 0.024) when pigs were fed 0.5% C6:0, 0.5% C8:0, or 0.5% C10:0 compared with control. An inclusion level × day interaction was observed (quadratic, P = 0.023), where PEDV Ct values increased (quadratic, P = 0.001) on 0 dpi with increasing levels of MCFA blend inclusion and also increased on 3 dpi (linear, P < 0.001). Fecal microbial diversity and composition were similar between control and 1.5% MCFA blend. In summary, the use of MCFA in nursery pig diets improves growth performance, provides residual mitigation activity against PEDV, and does not significantly alter fecal microbial composition.


Assuntos
Ração Animal/análise , Infecções por Coronavirus/veterinária , Ácidos Graxos/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Vírus da Diarreia Epidêmica Suína/efeitos dos fármacos , Doenças dos Suínos/prevenção & controle , Animais , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Dieta/veterinária , Fezes/microbiologia , Feminino , Masculino , Suínos , Doenças dos Suínos/virologia , Desmame
13.
Biosci Biotechnol Biochem ; 84(3): 606-612, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31746674

RESUMO

Royal jelly (RJ) is used as a dietary supplement for human health promotion. Recently, a clinical trial has reported that RJ improved mental health. The present study was conducted to experimentally support the clinical effect of RJ on mental health and to further elucidate the mechanisms of action of RJ. RJ and an ethanol extract of RJ, which contains fatty acids but not proteins, inhibited an unpredictable chronic mild stress (UCMS)-induced increase in immobility time, a depression-like behavior, in the tail suspension test. DNA microarray analysis of the adrenal grand revealed that the expression of genes involved in cholesterol metabolism was up-regulated in response to UCMS exposure and that RJ suppressed expression of genes related to cholesterol synthesis and transport. These results suggested that RJ improves stress-induced depression-like behavior by regulating adrenal steroidogenesis and that fatty acids contained in RJ partly contribute to the antidepressant effect of RJ.


Assuntos
Glândulas Suprarrenais/efeitos dos fármacos , Corticosterona/biossíntese , Depressão/prevenção & controle , Ácidos Graxos/farmacologia , Estresse Fisiológico , Glândulas Suprarrenais/metabolismo , Animais , Peso Corporal , Doença Crônica , Corticosterona/sangue , Depressão/tratamento farmacológico , Modelos Animais de Doenças , Expressão Gênica/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C
14.
Nat Prod Res ; 34(4): 474-481, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30295511

RESUMO

A new peroxy fatty acid, tagetnoic acid (5) [4-((3S,6S)-6-((3E,8E)-octadeca-3,8-dien-1-yl)-3,6-dihydro-1,2-dioxin-3-yl)butanoic acid] and four known metabolites: ecliptal (5-formyl-α-terthiophene) (1), 5-(4-hydroxybut-1-ynyl)-2,2'-bithiophene (2), 22,23-dihydrospinasterone (3), and stigmasterol (4) were separated from the n-hexane fraction of the aerial parts of Tagetes minuta L. (Asteraceae). Their chemical structures were verified using IR, UV, 2D and 1D NMR, and HRMS. Compounds 3-5 displayed potent lipoxygenase inhibitory potential with IC50s 2.26, 1.83, and 1.17 µM, respectively compared to indomethacin (IC50 0.89 µM). Moreover, molecular docking study revealed that the potent activity of 5 is due to H-bonding and hydrophobic interaction. The results of this study suggested that Tagetes minuta dietary consumption would be useful for the individuals at risk of acute and chronic inflammatory disorders.


Assuntos
Ácidos Graxos/isolamento & purificação , Inibidores de Lipoxigenase/isolamento & purificação , Extratos Vegetais/química , Tagetes/química , Ácidos Graxos/farmacologia , Humanos , Inflamação/tratamento farmacológico , Inibidores de Lipoxigenase/metabolismo , Inibidores de Lipoxigenase/farmacologia , Simulação de Acoplamento Molecular , Extratos Vegetais/farmacologia , Ligação Proteica , Arábia Saudita , Estigmasterol/isolamento & purificação , Tiofenos/isolamento & purificação
15.
Mol Cell Biochem ; 463(1-2): 45-55, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31630283

RESUMO

Adipose tissue inflammation is closely associated with the development of obesity and insulin resistance. Free fatty acids (FFAs) are a major inducer of obesity-related insulin resistance. Previously, we reported that endoplasmic reticulum (ER) stress potentially mediated retinal inflammation in diabetic retinopathy. The unfolded protein response (UPR) protects cells against damage induced by oxidative stress. X-box binding protein 1 (XBP1) plays a major role in protecting cells by modulating the UPR. However, the link between ER stress and adipocyte inflammation has been poorly investigated. In the present study, we found that pretreatment of 3T3-L1 adipocytes with a low dose of ER stress inducer tunicamycin inhibited FFA-induced upregulated expression of inflammatory cytokines. In addition, FFAs induced phosphorylation of the p65 subunit of NF-κB was largely inhibited by pretreatment with tunicamycin in 3T3-L1 adipocytes. Knockdown of XBP1 by siRNA markedly mitigated the protective effects of preconditioning against inflammation. Conversely, overexpression of XBP1 alleviated FFA-induced phosphorylation of IκB-α, IKKα/ß, and NF-κB, which was accompanied by decreased inflammatory cytokine expression. Collectively, these results imply a beneficial role of ER stress preconditioning in protecting against FFA-induced 3T3-L1 adipocyte inflammation, which is likely mediated through inhibition of the IKK/NF-κB pathway via XBP1.


Assuntos
Adipócitos/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Ácidos Graxos/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Proteína 1 de Ligação a X-Box/metabolismo , Células 3T3-L1 , Adipócitos/patologia , Animais , Citocinas/metabolismo , Ácidos Graxos/farmacologia , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Camundongos , Células RAW 264.7 , Tunicamicina/farmacologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-31884050

RESUMO

The mitochondrial phospholipid (CL) has been linked to mitochondrial and cellular functions. It has been postulated that the composition of CL is of impact for mitochondrial energy metabolism and cell proliferation. Although a correlation between CL composition and proliferation could be demonstrated for several cell types, evidence for a causal relationship remains obscure. Here, we applied two independent approaches, i) supplementation of fatty acids and ii) knock-out of the phospholipid remodeling enzyme tafazzin, to manipulate CL composition and analyzed the response on proliferation of C6 glioma cells. Both strategies caused substantial changes in the distribution of cellular fatty acids as well as in the distribution of fatty acids incorporated in CL that were accompanied by changes of the composition of molecular CL species. These changes did not correlate with cell proliferation. However, knock-out of tafazzin caused dramatic reduction in proliferation of C6 glioma cells independent of CL composition. The mechanism of tafazzin-dependent restriction of proliferation remains unclear. Among the various fatty acids administered only palmitic acid restricted cell proliferation by induction of cell death.


Assuntos
Aciltransferases/metabolismo , Neoplasias Encefálicas/metabolismo , Cardiolipinas/metabolismo , Glioma/metabolismo , Aciltransferases/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ácidos Graxos/farmacologia , Fosfolipídeos/metabolismo , Ratos
17.
Eur J Med Chem ; 185: 111810, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31678743

RESUMO

Ciprofloxacin (CP) has a confirmed cytotoxic action on some cancerous cells, but in high, non-pharmacological concentrations. Considering features of natural fatty acids, such as biocompatibility, biodegradability and their increased cellular uptake by cancer cells, it seems that combining them with a drug could improve its bioavailability, and thus cytotoxicity. Therefore, the aim of this study was coupling of CP with saturated and unsaturated fatty acids, and evaluation of their cytotoxicity, apoptosis-inducing effects and inhibition of IL-6 release in human primary (SW480) and metastatic (SW620) colon cancer, metastatic prostate cancer (PC3) and normal (HaCaT) cell lines. The PC3 cell line was the most sensitive to the presence of the obtained conjugates. The value of IC50 for oleic acid conjugate (4) was 7.7 µM, and it was 12 times lower than for CP alone (101.4 µM). The studied derivatives induced late apoptosis in all cancer cell lines, but not in normal cells. The most potent apoptosis inducer was conjugate 4, that resulted in the highest percentage of PC3 cells in late apoptosis (81.5% ±â€¯3.9), followed by elaidic acid amide 5 (75% ±â€¯4.8). The strongest pro-apoptic effects on SW480 cells were demonstrated by conjugates of DHA (8) and sorbic (2) acids, whereas in SW620 cell lines, compounds 2 and 5 appeared to be the most effective. To establish the mechanism of cytotoxic action of derivatives 2, 4, 5, the level of interleukin-6 (IL-6) was measured. The compounds with the highest cytotoxic potential significantly decreased the release of IL-6 by cancer cells. Additionally, all conjugates were evaluated for their in vitro antimicrobial activity. Short chain amides - crotonic (1) and sorbic (2) - were the most active against Staphyloccoci. The second-mentioned amide has shown both strong antistaphylococcal and antitumor properties.


Assuntos
Antineoplásicos/farmacologia , Ciprofloxacino/farmacologia , Ácidos Graxos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Antineoplásicos/síntese química , Antineoplásicos/química , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ciprofloxacino/síntese química , Ciprofloxacino/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Ácidos Graxos/síntese química , Ácidos Graxos/química , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade
18.
Toxicol Appl Pharmacol ; 386: 114833, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31756429

RESUMO

One of the main problems for the development of pulmonary formulations is the low availability of approved excipients. Polyglycerol esters of fatty acids (PGFA) are promising molecules for acting as excipient for formulation development and drug delivery to the lung. However, their biocompatibility in the deep lung has not been studied so far. Main exposed cells include alveolar epithelial cells and alveolar macrophages. Due to the poor water-solubility of PGFAs, the exposure of alveolar macrophages is expected to be much higher than that of epithelial cells. In this study, two PGFAs and their mixture were tested regarding cytotoxicity to epithelial cells and cytotoxicity and functional impairment of macrophages. Cytotoxicity was assessed by dehydrogenase activity and lactate dehydrogenase release. Lysosome function, phospholipid accumulation, phagocytosis, nitric oxide production, and cytokine release were used to evaluate macrophage function. Cytotoxicity was increased with the increased polarity of PGFA molecules. At concentrations above 1 mg/ml accumulation in lysosomes, impairment of phagocytosis, secretion of nitric oxide, and increased release of cytokines were noted. The investigated PGFAs in concentrations up to 1 mg/ml can be considered as uncritical and are promising for advanced pulmonary delivery of high powder doses and drug targeting to alveolar macrophages.


Assuntos
Excipientes/farmacologia , Excipientes/toxicidade , Ácidos Graxos/toxicidade , Glicerol/toxicidade , Polímeros/toxicidade , Células A549 , Administração por Inalação , Proteínas Aviárias/metabolismo , Citocinas/metabolismo , Excipientes/administração & dosagem , Ácidos Graxos/administração & dosagem , Ácidos Graxos/farmacologia , Glicerol/administração & dosagem , Glicerol/farmacologia , Humanos , Macrófagos/efeitos dos fármacos , Óxido Nítrico/biossíntese , Fagocitose/efeitos dos fármacos , Polímeros/administração & dosagem , Polímeros/farmacologia , Alvéolos Pulmonares/efeitos dos fármacos , Mucosa Respiratória/efeitos dos fármacos , Testes de Toxicidade
19.
Lipids Health Dis ; 18(1): 209, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796080

RESUMO

BACKGROUND: Consumption of a Western-styled diet enriched in saturated fatty acids (SFA) relative to polyunsaturated fatty acids is positively associated with risk for Alzheimer's disease. Whilst potential causal mechanism are unclear, there is increasing evidence that chronic ingestion of SFA enriched diets promote increase the plasma levels of lipoprotein-associated amyloid-ß (Aß). However, the effects of dietary mono- and poly-unsaturated fats (MUFA/PUFA) on nascent lipoprotein Aß abundance have not been previously reported. METHODS: Wild-type C57BL/6 J mice were maintained on low-fat control chow (LF) or diets enriched in either SFA, MUFA, or PUFA for 9 months. Enterocytic abundance of Aß was determined with quantitative immunofluorescent microscopy and plasma Aß was measured by ELISA. RESULTS: The chronic ingestion of SFA-enriched diet increased the enterocytic abundance and plasma concentration of Aß compared to LF control mice. The mice maintained on MUFA or PUFA diet showed comparable enterocytic and plasma Aß levels to the LF control mice. CONCLUSIONS: The data indicates that a diet enriched in SFA significantly increases the enterocytic Aß production and secretion into the circulation, whilst MUFA and PUFA enriched diet do not exert such effects.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Gorduras na Dieta/farmacologia , Enterócitos/efeitos dos fármacos , Ácidos Graxos Monoinsaturados/farmacologia , Ácidos Graxos Insaturados/farmacologia , Ácidos Graxos/farmacologia , Peptídeos beta-Amiloides/química , Animais , Enterócitos/metabolismo , Enterócitos/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Camundongos , Camundongos Endogâmicos C57BL
20.
Biomolecules ; 10(1)2019 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-31877674

RESUMO

Ximenia (Ximenia americana L.) is a shrub, or small tree, native from Africa and spread across different continents. In Angola, the seeds oil is used by local populations, to prevent sunburn, to smooth and hydrate the skin, and to give it a pleasant color and elasticity, to prevent stretch marks, in pregnant woman, and also as hair conditioner. Herein, an oil sold in the region (LPO), and two others extracted in laboratory, from seeds collected in the same region, were investigated in terms of their composition, chemical properties, UV transmission. The three oils are similar although the LPO is more acidic, 0.48 mg KOH/g. GC-MS analysis indicated that the major components are the fatty acids, oleic (31.82%), nervonic (11.09%), ximenic (10.22%), and hexacosa-17,20,23-trienoic acids (14.59%). Long chain fatty acids, n ≥ 20, accounted for 51.1% of the total fatty acids. A thin film of the oil showed a reduction in transmittance from 200 to 300 nm. Viscosity studies of the LPO indicated that at normal temperature of skin, the oil can be spread over the skin as a thin film. At concentrations up to 10 µg/mL, the LPO is not toxic to human keratinocytes, suggesting the safety of this oil.


Assuntos
Cosméticos/análise , Olacaceae/química , Óleos Vegetais/química , Angola , Ácidos Graxos/química , Ácidos Graxos/farmacologia , Humanos , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Óleos Vegetais/farmacologia , Sementes/química
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