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Over the past few years, metal nanowire networks have attracted attention as an alternative to transparent conducting oxide materials such as indium tin oxide for transparent conducting electrode applications. Recently, electrodeposition of metal on nanoscale template is widely used for formation of metal network. In the present work, junctionless Cu nanowire networks were simply fabricated on a substrate by forming a nanostructured Ru with 80 nm width as a seed layer, followed by direct electroless deposition of Cu. By controlling the density of Ru nanowires or the electroless deposition time, we readily achieve desired transmittance and sheet resistance values ranging from â¼1 kΩ sq-1at 99% to 9 Ω sq-1at 89%. After being transferred to flexible substrates, the nanowire networks exhibited no obvious increase in resistance during 8000 cycles of a bending test to a radius of 2.5 mm. The durability was verified by evaluation of its heating performance. The maximum temperature was greater than 180 °C at 3 V and remained constant after three repeated cycles and for 10 min. Transmission electron microscopy and x-ray diffraction studies revealed that the adhesion between the electrolessly deposited Cu and the seed Ru nanowires strongly influenced the durability of the core-shell structured nanowire-based heaters.
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Objectives: Although mulberry fruit possesses some biological activities, it is not known how it protects neuronal cells in neurodegenerative diseases. Here, we examined whether mulberry fruit extract (MFE) protected neuronal cells against oxidative stress-induced neurodegeneration.Methods: In this experiments, glutamate challenged hippocampal neuronal HT-22 cell lines as an in vitro model and scopolamine-induced memoty-impairment mice model were used.Results: MFE improved cell viability and glutathione level as well as reducing reactive oxygen species level in glutamate-treated HT-22 cells. Additionally, MFE suppressed apoptotic bodies and mitochondrial depolarization through regulating expression of apoptosis-related proteins. Furthermore, MFE elevated expression of p-TrkB, p-Akt, p-CREB, BDNF, and antioxidant enzymes as well as nuclear translocation of Nrf2. In contrast, the inclusion of K252a, a TrkB inhibitor, or MK-2206, an Akt selective inhibitor, neutralized the neuroprotective actions of MFE. Separately, MFE attenuated scopolamine-induced amnesia via regulating the activities of enzymes related with cholinergic function and the antioxidant system in mice. Additionally, MFE protected neuronal cells in the hippocampal CA1 and CA3 regions in brain of mice.Conclusions: MFE protects neuronal cells against oxidative stress-induced apoptosis through upregulating the expression of BDNF and antioxidant enzymes by stabilizing the activation of the TrkB/Akt pathway. Such an effect of MFE, which includes rich polyphenols, may provide information for its application as a food supplement for the prevention and treatment of neurodegenerative diseases.
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Antioxidantes , Colinérgicos , Transtornos da Memória/tratamento farmacológico , Morus , Extratos Vegetais/administração & dosagem , Receptor trkB/fisiologia , Animais , Apoptose/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/genética , Linhagem Celular , Frutas/química , Ácido Glutâmico/farmacologia , Hipocampo/citologia , Masculino , Transtornos da Memória/induzido quimicamente , Camundongos , Camundongos Endogâmicos ICR , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Fármacos Neuroprotetores , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/fisiologia , Receptor trkB/antagonistas & inibidores , Escopolamina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Regulação para CimaRESUMO
In this study, we found that E. prolifera extract (EAEP) exhibits neuroprotective effects in oxidative stress-induced neuronal cells. EAEP improved cell viability as well as attenuated the formation of intracellular reactive oxygen species (ROS) and apoptotic bodies in glutamate-treated hippocampal neuronal cells (HT-22). Furthermore, EAEP improved the expression of brain-derived neurotrophic factor (BDNF) and antioxidant enzymes such as heme oxygenase-1 (HO-1), NAD(P)H quinine oxidoreductase-1 (NQO-1), and glutamate-cysteine ligase catalytic subunit (GCLC) via the tropomyosin-related kinase receptor B/ protein kinase B (TrkB/Akt) signaling pathway. In contrast, the pre-incubation of K252a, a TrkB inhibitor, or MK-2206, an Akt-selective inhibitor, ameliorated the neuroprotective effects of EAEP in oxidative stress-induced neuronal cells. These results suggest that EAEP protects neuronal cells against oxidative stress-induced apoptosis by upregulating the expression of BDNF and antioxidant enzymes via the activation of the TrkB/Akt pathway. In conclusion, such an effect of EAEP, which is rich in carotenoid-derived compounds, may justify its application as a food supplement in the prevention and treatment of neurodegenerative disorders.
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Antioxidantes/farmacologia , Carotenoides/farmacologia , Hipocampo/efeitos dos fármacos , Glicoproteínas de Membrana/metabolismo , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Alga Marinha/química , Animais , Antioxidantes/isolamento & purificação , Apoptose/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Carotenoides/isolamento & purificação , Linhagem Celular , Ácido Glutâmico/toxicidade , Hipocampo/enzimologia , Hipocampo/patologia , Camundongos , Neurônios/enzimologia , Neurônios/patologia , Fármacos Neuroprotetores/isolamento & purificação , Transdução de SinaisRESUMO
The purpose of this study is to evaluate the effect of N-arachidonoyl serotonin (NA-5HT) on inflammatory response or oxidative stress in RAW264.7 cells exposed to lipopolysaccharide (LPS). When RAW264.7 cells were pre-incubated with NA-5HT before LPS treatment, NA-5HT was found to suppress LPS-induced formation of nitric oxide (NO), tumor necrosis factor-α or interleukins as well as expression of inducible NO synthase and cyclooxygenase-2 at non-cytotoxic concentrations. Consistent with this, NA-5HT efficiently reversed LPS-induced phosphorylative activation of nuclear factor-κB pathway probably through the suppression of mitogen-activated protein kinases (MAPKs) pathway or phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. Separately, NA-5HT enhanced the antioxidant capacity accompanied by nuclear translocation of nuclear factor-E2-related factor-2 (Nrf2) in RAW264.7 cells. Additionally, NA-5HT-induced nuclear translocation of Nrf2 was suppressed significantly by the inhibition of c-Jun N-terminal kinase1/2 or PI3K/Akt pathways, although NA-5HT phosphorylated signal molecules in MAPKs and PI3K/Akt pathways. Taken together, NA-5HT is proposed to exert anti-inflammatory and antioxidant actions in RAW264.7 cells.
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Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Ácidos Araquidônicos/farmacologia , Serotonina/análogos & derivados , Serotonina/farmacologia , Animais , Linhagem Celular , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Glutationa/metabolismo , Quinase I-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , Malondialdeído/metabolismo , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
The dopamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) is widely used as a therapeutic choice for the treatment of patients with Parkinson's disease. However, the long-term use of L-DOPA leads to the development of debilitating involuntary movements, called L-DOPA-induced dyskinesia (LID). The cAMP/protein kinase A (PKA) signaling in the striatum is known to play a role in LID. However, from among the nine known adenylyl cyclases (ACs) present in the striatum, the AC that mediates LID remains unknown. To address this issue, we prepared an animal model with unilateral 6-hydroxydopamine lesions in the substantia nigra in wild-type and AC5-knock-out (KO) mice, and examined behavioral responses to short-term or long-term treatment with L-DOPA. Compared with the behavioral responses of wild-type mice, LID was profoundly reduced in AC5-KO mice. The behavioral protection of long-term treatment with L-DOPA in AC5-KO mice was preceded by a decrease in the phosphorylation levels of PKA substrates ERK (extracellular signal-regulated kinase) 1/2, MSK1 (mitogen- and stress-activated protein kinase 1), and histone H3, levels of which were all increased in the lesioned striatum of wild-type mice. Consistently, FosB/ΔFosB expression, which was induced by long-term L-DOPA treatment in the lesioned striatum, was also decreased in AC5-KO mice. Moreover, suppression of AC5 in the dorsal striatum with lentivirus-shRNA-AC5 was sufficient to attenuate LID, suggesting that the AC5-regulated signaling cascade in the striatum mediates LID. These results identify the AC5/cAMP system in the dorsal striatum as a therapeutic target for the treatment of LID in patients with Parkinson's disease.
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Inibidores de Adenilil Ciclases , Antiparkinsonianos/efeitos adversos , Discinesia Induzida por Medicamentos/enzimologia , Levodopa/efeitos adversos , Transtornos Parkinsonianos/metabolismo , Adenilil Ciclases , Animais , Western Blotting , Modelos Animais de Doenças , Discinesia Induzida por Medicamentos/prevenção & controle , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Some endocannabinoids have been known to express anti-inflammatory and antioxidant actions independent of cannabinoid receptors. In this respect, we investigated whether N-acyl 5-hydroxytryptamines (5-HTs) might prevent against glutamate-induced oxidative cytotoxicity in HT-22 cells, and attempted to elucidate the mechanism for their cytoprotective action. N-acyl 5-HTs with palmitoyl, stearoyl, arachidonoyl or docosahexaenoyl chain expressed a remarkable protective effect on glutamate-induced cytotoxicity. Additionally, glutamate-induced oxidative stress, represented by the increase of reactive oxygen species level and the reduction of glutathione level, was prevented markedly by N-acyl 5-HTs at submicromolar levels. Further, N-palmitoyl 5-HT, the most cytoprotective, enhanced antioxidant defense by up-regulating the expression of antioxidant enzymes such as heme oxygenase-1, glutamate-cysteine ligase catalytic subunit or NAD(P)H quinine oxidoreductase-1 in the presence or absence of glutamate. Consistent with this, N-palmitoyl 5-HT stimulated nuclear translocation of Nrf2 in early phase (2 h), and this effect was remarkably suppressed by inhibitors of PI3K, PDK-1, Akt or p38 MAPK. Additionally, N-palmitoyl 5-HT suppressed glutamate-induced activation of ERK in late phase (12 h), but not in early phase (2 h), presumably supporting the implication of MEK/ERK pathway in glutamate-induced cytotoxicity. Collectively, it is suggested that N-acyl 5-HTs may attenuate glutamate-induced cytotoxicity via the activation of PI3K/PDK-1/Akt- and p38 MAPK-dependent Nrf2 signaling in early phase as well as the suppression of MEK/ERK pathway in late phase.
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Glutamina/toxicidade , Fármacos Neuroprotetores/farmacologia , Serotonina/farmacologia , Western Blotting , Linhagem Celular , Humanos , Sistema de Sinalização das MAP QuinasesRESUMO
Endocannabinoids appear to be involved in a variety of physiological processes. Lipoxygenase activity has been known to be affected by unsaturated fatty acids or phenolic compounds. In this study, we examined whether endocannabinoids containing both N-acyl group and phenolic group can affect the activity of soybean lipoxygenase (LOX)-1, similar to mammalian 15-lipoxygenase in physicochemical properties. First, N-arachidonoyl dopamine and N-oleoyl dopamine were found to inhibit soybean LOX-1-catalyzed oxygenation of linoleic acid in a non-competitive manner with a Ki value of 3.7 µM and 6.2 µM, respectively. Meanwhile, other endocannabinoids failed to show a remarkable inhibition of soybean LOX-1. Separately, N-arachidonoyl dopamine and N-arachidonoyl serotonin were observed to inactivate soybean LOX-1 with Kin value of 27 µM and 24 µM, respectively, and k3 value of 0.12 min(-1) and 0.35 min(-1), respectively. Furthermore, such an inactivation was enhanced by ascorbic acid, but suppressed by 13(S)-hydroperoxy-9,11-octadecadienoic acid. Taken together, it is proposed that endocannabinoids containing polyunsaturated acyl moiety and phenolic group may be efficient for the inhibition as well as inactivation of 15-lipoxygenase.
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Endocanabinoides/farmacologia , Inibidores Enzimáticos/farmacologia , Glycine max/enzimologia , Lipoxigenase/metabolismo , Biocatálise/efeitos dos fármacos , Relação Dose-Resposta a Droga , Endocanabinoides/química , Inibidores Enzimáticos/química , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: The aim of this study was to examine the inflammation induced by saturated acyl lysophosphatidylcholine (LPC) in vivo and to investigate whether it could be attenuated by the action of polyunsaturated acyl lysophosphatidylcholines (LPCs), which are known as anti-inflammatory lipid mediators. METHODS: First, saturated acyl LPC was administered intraperitoneally (i.p.) to mice and the inflammatory profile was extensively characterized. Subsequently, the preventive effect of polyunsaturated acyl LPCs, i.p. administered 30 min after saturated acyl LPC, was evaluated by measuring indices of inflammation such as leukocyte migration, plasma leakage, and eicosanoid or cytokine formation by light microscopy, Evans blue dye as indicator, and enzyme-linked immunosorbent assay, respectively. RESULTS: Saturated acyl LPCs as LPC16:0 (100 mg/kg, i.p.) proved to be an effective inflammation inducer which causes a significant increase in plasma leakage, leukocyte migration into peritoneum and elevation of pro-inflammatory mediators. Interestingly, LPC20:4 and LPC22:6 (50 and 150 µg/kg) significantly nullified LPC16:0-induced inflammation. The anti-inflammatory effects of LPC20:4 and LPC22:6 were related to down-regulation of leukocyte extravasation, plasma leakage, and formation of pro-inflammatory mediators (IL-5, IL-6, NO, 12-HETE and PGE(2)) stimulated by LPC16:0, and up-regulation of anti-inflammatory mediators (IL-4 and IL-10). CONCLUSION: These results indicated that the pro-inflammatory activity of saturated acyl LPCs could be antagonized by the actions of polyunsaturated acyl LPCs, anti-inflammatory lipid mediators.
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Anti-Inflamatórios/farmacologia , Inflamação/induzido quimicamente , Lisofosfatidilcolinas/farmacologia , Animais , Permeabilidade Capilar/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Leucócitos/efeitos dos fármacos , Leucócitos/fisiologia , Lisofosfatidilcolinas/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos ICRRESUMO
Antioxidant ingredients are known to contribute to the beneficial effects of natural products in health promotion as well as disease prevention by reducing oxidative stress, caused by reactive oxygen or nitrogen species, in biological systems [...].
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In present study, lysophospholipase C (lysoPLC) was purified from homogenate of pig brain. LysoPLC was purified from brain membranes by procedures employing acetic acid precipitation, 1-butanol solubilization and ammonium sulfate fractionation, and chromatographies. In SDS-PAGE, the purified enzyme protein was relatively homogeneous with molecular mass of around 65 kDa. The lysoPLC activity possesses an optimal pH of 8.5, and Km and Vm values of 120.3 microM, and 141.6 micromole/h/mg protein, respectively for 1-lauroyl lysophosphatidylcholine(LPC), and 72.4 microM and 89.8 micromole/h/mg protein for glycerophosphorylcholine (GPC). In thermal denaturation at 60 degrees C, the enzyme expressed the same inactivation pattern in the hydrolysis of 1-lauroyl LPC and GPC. In the structure activity relationship, catalytic efficacy (Vm/Km value) was the greatest for 1-docosahexaenoyl LPC, followed by 1-arachidonoyl LPC, GPC, 1-hexanoyl LPC, 1-lauroyl LPC, 1-linoleoyl LPC, 1-myristoyl LPC and 1-oleoyl LPC. Metal ion requirement indicates that Zn(2+) was crucial for lysoPLC activity. Noteworthy, in the inhibition by oxyanions, the enzyme was selectively and noncompetitively inhibited by tellurite ions with Ki value of 0.16 and 0.18 microM in hydrolyzing 1-lauroyl LPC and GPC, respectively. Taken together, it is suggested that lysoPLC, possessing broad substrate specificity, may be implicated in the supply of phosphocholine in brain tissue.
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Encéfalo/enzimologia , Lisofosfolipase/isolamento & purificação , Animais , Cromatografia Líquida , Eletroforese em Gel de Poliacrilamida , Lisofosfolipase/metabolismo , Desnaturação Proteica , SuínosRESUMO
BACKGROUND: Solvent fractionation is effective in improving separation at low temperature, resulting in higher yield and purity of the final product. Tripalmitin (PPP) is an important substrate for the synthesis of human milk fat substitute (HMFS). In this study a fraction rich in PPP was separated from palm stearin by solvent fractionation. RESULTS: The PPP-rich fraction was concentrated from palm stearin by acetone fractionation. Response surface methodology (RSM) was employed to optimise PPP purity (Y(1), %) and PPP content (Y(2), g kg(-1) palm stearin) with the independent variables fractionation temperature (X(1), 25, 30 and 35 degrees C) and weight ratio of palm stearin to acetone (X(2), 1:3, 1:6 and 1:9). The predictive models for PPP purity and PPP content of the solid fraction were adequate and reproducible, with no significant lack of fit and satisfactory levels of R(2). PPP purity showed a positive correlation with temperature and acetone ratio, whereas PPP content exhibited a negative correlation. The optimised fractionation condition for a targeted PPP-rich fraction with > 92% PPP purity and > 225 g kg(-1) PPP content from palm stearin was predicted. CONCLUSION: The RSM model for optimising PPP purity and PPP content in the PPP-rich fraction from palm stearin by acetone fractionation was valid. The scaled-up PPP-rich fraction obtained can be used as a substrate for the synthesis of 1,3-dioleoyl-2-palmitoylglycerol, which is a main component of HMFS in infant formulas.
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Fracionamento Químico/métodos , Óleos de Plantas/química , Triglicerídeos/isolamento & purificação , Fenômenos Químicos , Cromatografia Líquida de Alta Pressão , Ácidos Graxos/análise , Glicerol/análogos & derivados , Glicerol/química , Modelos Estatísticos , Óleo de Palmeira , Reprodutibilidade dos Testes , Solventes , Temperatura , Temperatura de Transição , Triglicerídeos/químicaRESUMO
Although mulberry fruit has various beneficial effects, its effect on diabetes-related dementia remains unknown. We investigated whether the ethyl acetate fraction of ethanolic extract of mulberry fruit (MFE) could alleviate biochemical and behavioral deficits in alloxan-induced diabetic mice. In the diabetic mice, MFE considerably abolished multiple deficits, e.g., body weight reduction; water and food intake increase; and hyperglycemia, hyperlipidemia, hypoinsulinism, and hypertrophy of the liver, kidneys, spleen, and brain. A 200 mg/kg MFE dose reduced malondialdehyde levels and improved antioxidant enzyme activity in the liver, kidney, and brain tissues. MFE attenuated hyperglycemia-induced memory impairments and acetylcholine deprivation, protected neuronal cells in CA1 and CA3 regions via p-CREB/BDNF pathway activation, and reduced amyloid-ß precursor protein and p-Tau expressions in the brain tissue. In conclusion, MFE exerts antidiabetic and neuroprotective effects by upregulating antioxidative activities and p-CREB/BDNF pathway in chronic diabetes. Therefore, MFE may be used as a therapeutic agent for diabetes and diabetic neurodegenerative diseases.
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Antioxidantes/metabolismo , Glicemia/metabolismo , Demência/prevenção & controle , Diabetes Mellitus Experimental/prevenção & controle , Frutas/química , Morus/química , Transdução de Sinais , Regulação para Cima , Aloxano , Peptídeos beta-Amiloides/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Demência/sangue , Demência/tratamento farmacológico , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Hipolipemiantes/farmacologia , Hipolipemiantes/uso terapêutico , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos ICR , Especificidade de Órgãos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Proteínas tau/metabolismoRESUMO
In recent years, growth hormone deficiency in children has been treated with hormone therapy despite the possible significant side effects. Therefore, it was deemed beneficial to develop functional foods or dietary supplements for safely improving children's growth. Spirulina platensis is known for its high antioxidant, anti-aging, anti-cancer, and immunity-enhancing properties, as well as its high digestibility and high protein content, but little has been reported about its influence on bone development in children with a normal supply of protein. In this study, we evaluated the effects of spirulina on the bone metabolism and antioxidant profiles of three-week-old growing male rats. The animals were divided into four groups (n = 17 per group) and were fed AIN93G diets with 0% (control), 30% (SP30), 50% (SP50), and 70% (SP70) of casein protein replaced by spirulina, respectively, for seven weeks. We observed that spirulina enhanced bone growth and bone strength by stimulating parathyroid hormone and growth hormone activities, as well its increased antioxidant activity. These results indicate that spirulina provides a suitable dietary supplement and alternative protein source with antioxidant benefits for growth improvement in early developmental stages.
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Desenvolvimento Ósseo , Osso e Ossos/metabolismo , Suplementos Nutricionais , Alimento Funcional , Hormônios/metabolismo , Spirulina , Ração Animal , Animais , Antioxidantes , Biomarcadores , Peso Corporal , Densidade Óssea , Osso e Ossos/anatomia & histologia , Osso e Ossos/diagnóstico por imagem , Hormônio do Crescimento , Peróxidos Lipídicos/metabolismo , Lipídeos/sangue , Masculino , Tamanho do Órgão , Ratos , Resistência à TraçãoRESUMO
Enteromorpha prolifera, a green alga, has long been used in food diets as well as traditional remedies in East Asia. Our preliminary study demonstrated that an ethyl acetate extract of Enteromorpha prolifera (EAEP) exhibited the strongest antioxidant activity compared to ethanol or water extracts. Nonetheless, there has been no report on the effect of EAEP on memory impairment due to oxidative damage. This study investigated whether EAEP could attenuate memory deficits in an oxidative stress-induced mouse model. EAEP was orally administered (50 or 100 mg/kg body weight (b.w.)) to mice and then scopolamine was administered. The oral administration of EAEP at 100 mg/kg b.w. significantly restored memory impairments induced by scopolamine, as evaluated by the Morris water maze test, and the passive avoidance test. Further, EAEP upregulated the protein expression of BDNF, p-CREB, p-TrkB, and p-Akt. Moreover, EAEP downregulated the expression of amyloid-ß, tau, and APP. The regulation of cholinergic marker enzyme activities and the protection of neuronal cells from oxidative stress-induced cell death in the brain of mice via the downregulation of amyloid-ß and the upregulation of the BDNF/TrkB pathway by EAEP suggest its potential as a pharmaceutical candidate to prevent neurodegenerative diseases.
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Ribes diacanthum Pall (RDP) is a Mongolian traditional medicine used to treat renal inflammation. In the present study, we initially investigated the anti-inflammatory effects and mechanisms of action of ethylacetate extract of RDP (EARDP) in RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS) and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced dermatitis in mice. We demonstrated that EARDP protected against LPS-induced cell death by inhibiting intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) production, as well as the synthesis of pro-inflammatory mediators and cytokines, such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1ß. EARDP inhibited the phosphorylation and degradation of inhibitory κB-α (IκB-α) and the activation of nuclear factor (NF)-κB, indicating that the anti-inflammatory effect of EARDP was mediated via the suppression of NF-κB nuclear translocation. In addition, EARDP induced the heme oxygenase-1 (HO-1) expression and nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2), indicating that EARDP induced HO-1 via the Nrf2 pathway in RAW 264.7 cells. Furthermore, EARDP significantly suppressed the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW 264.7 macrophages. However, ZnPP, a specific inhibitor of HO-1, reversed the EARDP-mediated inhibition of NO and TNF-α production in LPS-stimulated RAW 264.7 macrophages. EARDP blocked the phosphorylation of mitogen-activated protein kinase (MAPK) and Akt in LPS-stimulated RAW 264.7 cells. In the in vivo animal model, EARDP significantly and dose-dependently reduced TPA-induced secretion of TNF-α and IL-6 in mouse ear. Based on these results, EARDP represents a promising natural compound, protective against oxidative stress and inflammatory diseases.
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Ribes diacanthum Pall, a native Mongolian medicinal plant, has been reported to show antioxidant activities due to its polyphenol and flavonoid content, and is especially rich in the ethyl acetate fraction from an 80% methanol extraction (RDP). We assessed the cytoprotective effect of RDP on glutamate-caused oxidative stress and apoptosis in mouse hippocampal neuronal cells (HT-22 cells). Cell viability was significantly recovered by RDP treatment. Also, RDP effectively decreased the glutamate-induced production of intracellular reactive oxygen species (ROS). In flow cytometric analysis, apoptotic cells and the mitochondrial membrane potential were suppressed by RDP. In the Western blotting analysis, we found that RDP not only decreased the release of apoptotic proteins but also recovered anti-apoptotic protein. Additionally, RDP enhanced the antioxidant defense system by regulating the expression of antioxidant enzymes. Furthermore, treatment with RDP activated the BDNF/TrkB pathway. In accordance with the in vitro results, RDP meliorated memory deficit by defending hippocampal neuronal cells against oxidative damage in scopolamine-injected mice. Taken together, our present study showed that RDP exerted antioxidant and neuroprotective actions against oxidative stress. Therefore, RDP might facilitate the development of candidates for functional health foods for neurodegenerative disorders.
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Silkworm pupae (Bombyx mori) is an edible insect that has been reported to contain high-quality proteins, lipids, minerals, and vitamins, and to possess high antioxidant activity. However, there have been no studies on the neuroprotective effects of silkworm pupae. Therefore, we investigated a water extract of silkworm pupae with protease (WSP) as a functional and therapeutic candidate for neurodegenerative disorders. First, we evaluated the effect of WSP on oxidative stress-induced mouse hippocampal neuronal cells (HT-22 cells). Cell viability diminished by addition of glutamate but was significantly recovered by WSP treatment. Furthermore, WSP significantly decreased the release of lactate dehydrogenase and generation of intracellular reactive oxygen species in oxidative stress-induced cells. In addition, in scopolamine-treated mice, WSP attenuated memory impairment, as demonstrated in the Morris water maze and passive avoidance tests, indicating protection of neuronal cells against oxidative damage. Moreover, WSP prevented scopolamine-induced increases in acetylcholinesterase activity and decreases in choline-acetyltransferase activity. Finally, treatment with WSP enhanced the antioxidant defense system by regulating the activities of antioxidant enzymes. Overall, this study showed that WSP exerted antioxidant and memory enhancing action against oxidative stress.
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Arachidonic acid, released from PLA(2) hydrolysis of phosphatidylcholine, is converted to pro-inflammatory or anti-inflammatory mediators. Although lysophosphatidylcholine (lysoPC), another product, is known to be pro-inflammatory, the role of polyunsaturated lysoPCs is not clear. Here, we examined the role of arachidonoyl-lysoPC and its lipoxygenation product in inflammation. First, when the effect of arachidonoyl-lysoPC, administrated i.v., on zymosan A-induced plasma leakage in mice was examined, arachidonoyl-lysoPC was found to prevent zymosan A-induced plasma leakage remarkably. As the interval time between lysoPC administration and zymosan A challenge was extended, the suppression of plasma leakage was augmented, suggesting that a metabolism of arachidonoyl-lysoPC may be implicated in anti-inflammatory action. Additionally, 4-methyl-2-(4-methylpiperazinyl)pyrimido[4,5-b] benzothiazine, an inhibitor of 15-lipoxygenase, was found to diminish the suppressive action of arachidonyl-lysoPC, indicating that 15-HPETE-lysoPC may be a metabolite responsible for anti-inflammatory action of arachidonoyl-lysoPC. In support of this, 15-HPETE-lysoPC (ED(50), 32 microg/kg) exhibited a greater anti-inflammatory action than arachidonoyl-lysoPC. Further, mechanistic analysis indicates that anti-inflammatory action of 15-HPETE-lysoPC was related largely to the formation of lipoxin, and to less extent to the inhibition of LTC biosynthesis, but not to PGE formation. Further, i.p. administration of arachidonoyl-lysoPC or 15-HPETE-lysoPC also exhibited a dose-dependent effect, although less efficient than i.v. injection. Additionally, the time-dependent suppression was more remarkable for 15-HPETE-lysoPC than arachidonoyl-lysoPC, suggestive of different mechanisms for anti-inflammatory action in peritoneum. Taken together, it is proposed that arachidonoyl-lysoPC and its oxidation product may belong to endogenous lipids displaying anti-inflammatory effects in vivo.
Assuntos
Anti-Inflamatórios/farmacologia , Leucotrienos/farmacologia , Peróxidos Lipídicos/farmacologia , Inibidores de Lipoxigenase/farmacologia , Peritonite/tratamento farmacológico , Animais , Ácido Araquidônico/farmacologia , Dinoprostona/metabolismo , Leucotrieno C4/metabolismo , Lipoxinas/metabolismo , Lisofosfatidilcolinas/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Lavagem Peritoneal , Peritonite/imunologia , Peritonite/metabolismoRESUMO
The present study was undertaken to assess the beneficial effects of a daily consumption of 8 % freeze-dried red-pigmented leafy lettuce (Lactuca sativa) on CVD. C57BL/6J mice were fed a high-fat high-cholesterol diet supplemented with or without red-pigmented leafy lettuce for 4 weeks. The present results showed that the red-pigmented leafy lettuce-supplemented diet significantly decreased the level of total and LDL-cholesterol and TAG in the plasma of the mice. The atherosclerotic index was calculated to be 46 % lower in the mice fed with the lettuce diet compared with the control diet. Lipid peroxidation measured by 2-thiobarbituric acid-reactive substances was markedly reduced in the plasma, liver, heart and kidney of the mice fed the lettuce diet. The content of antioxidants (total glutathione and beta-carotene) was significantly increased by lettuce supplementation. The antioxidant defence system by antioxidant enzymes including glutathione S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase and paraoxanase in blood or liver tissues was also increased, and showed the improved oxidative stress in the mice fed the lettuce diet. The measurement of tail DNA (%), tail extent moment and olive tail moment indicated that the lettuce diet increased the resistance of hepatocyte and lymphocyte DNA to oxidative damage. The present study showed that the supplementation of a high-cholesterol high-fat diet with 8 % red-pigmented leafy lettuce resulted in an improvement of plasma cholesterol and lipid levels, prevention of lipid peroxidation and an increase of the antioxidant defence system and, therefore, could contribute to reduce the risk factors of CVD.
Assuntos
Antioxidantes/metabolismo , Gorduras na Dieta/administração & dosagem , Suplementos Nutricionais , Lactuca/química , Peroxidação de Lipídeos/fisiologia , Animais , Peso Corporal/fisiologia , Colesterol na Dieta/administração & dosagem , Dano ao DNA , Dieta , Ingestão de Alimentos/fisiologia , Fezes/química , Hepatócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/fisiologia , Pigmentos Biológicos/análiseRESUMO
This study was performed to investigate the effect of aged black garlic ethyl acetate extract on scopolamine-induced cognitive impairment in mice. Aged garlic ethyl acetate extract (BG) was administrated at a dose of 25 or 50 mg/ kg in scopolamine-induced mice. Cognitive ability was evaluated using a Morris water maze test and a passive avoidance test. BGs (50 mg/kg) shortened the latency time that was increased by scopolamine and increased the platform crossing numbers that was significantly shortened by scopolamine after 5 days training in the Morris water maze test (P<0.05). BG (50 mg/kg) also significantly prolonged the latency time in the passive avoidance test (P<0.05). Result from biochemical analysis showed that BG increased levels of glutathione, glutathione peroxidase activity, and glutathione reductase activity, whereas BG significantly inhibited lipid peroxidation (P<0.05). BG also attenuated cholinergic degradation through inhibiting acetylcholinesterase activity and increasing choline acetyltransferase activity (P<0.05). In conclusion, BG protected against scopolamine-induced cognitive impairment through decreasing oxidative damage and regulating cholinergic function in the brains of mice. BG may therefore be a beneficial food for protecting against neurodegeneration such as Alzheimer's disease.