RESUMO
Active hydroponic substrates that stimulate on demand the plant growth have not been demonstrated so far. Here, we developed the eSoil, a low-power bioelectronic growth scaffold that can provide electrical stimulation to the plants' root system and growth environment in hydroponics settings. eSoil's active material is an organic mixed ionic electronic conductor while its main structural component is cellulose, the most abundant biopolymer. We demonstrate that barley seedlings that are widely used for fodder grow within the eSoil with the root system integrated within its porous matrix. Simply by polarizing the eSoil, seedling growth is accelerated resulting in increase of dry weight on average by 50% after 15 d of growth. The effect is evident both on root and shoot development and occurs during the growth period after the stimulation. The stimulated plants reduce and assimilate NO3- more efficiently than controls, a finding that may have implications on minimizing fertilizer use. However, more studies are required to provide a mechanistic understanding of the physical and biological processes involved. eSoil opens the pathway for the development of active hydroponic scaffolds that may increase crop yield in a sustainable manner.
Assuntos
Fenômenos Biológicos , Plântula , Plântula/metabolismo , Hidroponia/métodos , Raízes de Plantas/metabolismoRESUMO
Nitrogen (N) fertilization increases biomass and soil organic carbon (SOC) accumulation in boreal pine forests, but the underlying mechanisms remain uncertain. At two Scots pine sites, one undergoing annual N fertilization and the other a reference, we sought to explain these responses. We measured component fluxes, including biomass production, SOC accumulation, and respiration, and summed them into carbon budgets. We compared the resulting summations to ecosystem fluxes measured by eddy covariance. N fertilization increased most component fluxes (P < 0.05), especially SOC accumulation (20×). Only fine-root, mycorrhiza, and exudate production decreased, by 237 (SD = 28) g C m-2 yr-1 . Stemwood production increases were ascribed to this partitioning shift, gross primary production (GPP), and carbon-use efficiency, in that order. The methods agreed in their estimates of GPP in both stands (P > 0.05), but the components detected an increase in net ecosystem production (NEP) (190 (54) g C m-2 yr-1 ; P < 0.01) that eddy covariance did not (19 (62) g C m-2 yr-1 ; ns). The pairing of plots, the simplicity of the sites, and the strength of response provide a compelling description of N effects on the C budget. However, the disagreement between methods calls for further paired tests of N fertilization effects in simple forest ecosystems.
Assuntos
Ecossistema , Pinus sylvestris , Carbono , Árvores/fisiologia , Nitrogênio , Solo , Florestas , Dióxido de CarbonoRESUMO
Understanding how plant water uptake interacts with acquisition of soil nitrogen (N) and other nutrients is fundamental for predicting plant responses to a changing environment, but it is an area where models disagree. We present a novel isotopic labelling approach which reveals spatial patterns of water and N uptake, and their interaction, by trees. The stable isotopes 15 N and 2 H were applied to a small area of the forest floor in stands with high and low soil N availability. Uptake by surrounding trees was measured. The sensitivity of N acquisition to water uptake was quantified by statistical modelling. Trees in the high-N stand acquired twice as much 15 N as in the low-N stand and around half of their N uptake was dependent on water uptake (2 H enrichment). By contrast, in the low-N stand there was no positive effect of water uptake on N uptake. We conclude that tree N acquisition was only marginally dependent on water flux toward the root surface under low-N conditions whereas under high-N conditions, the water-associated N uptake was substantial. The results suggest a fundamental shift in N acquisition strategy under high-N conditions.
Assuntos
Pinus sylvestris , Árvores , Nitrogênio/análise , Solo , Taiga , ÁguaRESUMO
We report results from long-term simulated external nitrogen (N) input experiments in three northern Pinus sylvestris forests, two of moderately high and one of moderately low productivity, assessing effects on annual net primary production (NPP) of woody mass and its interannual variation in response to variability in weather conditions. A sigmoidal response of wood NPP to external N inputs was observed in the both higher and lower productivity stands, reaching a maximum of ~65% enhancement regardless of the native site productivity, saturating at an external N input of 4-5 g N·m-2 ·yr-1 . The rate of increase in wood NPP and the N response efficiency (REN , increase in wood NPP per external N input) were maximized at an external N input of ~3 g N·m-2 ·yr-1 , regardless of site productivity. The maximum REN was greater in the higher productivity than the lower productivity stand (~20 vs. ~14 g C/g N). The N-induced enhancement of wood NPP and its REN were, however, markedly contingent on climatic variables. In both of the higher and lower productivity stands, wood NPP increased with growing season precipitation (P), but only up to ~400 mm. The sensitivity of the response to P increased with increasing external N inputs. Increasing growing season temperature (T) somewhat increased the N-induced drought effect, whereas decreasing T reduced the drought effect. These responses of wood NPP infused a large temporal variation to REN , making the use of a fixed value unadvisable. Based on these results, we suggest that regional climate conditions and future climate scenarios should be considered when modeling carbon sequestration in response to N deposition in boreal P. sylvestris, and possibly other forests.
Assuntos
Sequestro de Carbono , Clima , Florestas , Nitrogênio/metabolismo , Pinus sylvestris/metabolismo , Noruega , Estações do Ano , Suécia , Árvores/metabolismo , Madeira/química , Madeira/metabolismoRESUMO
Microglial-mediated neuroinflammation has recently been implicated as one of the important mechanisms responsible for the progression of neurodegenerative diseases. Activated microglia cells produce various neurotoxic factors that are harmful to neurons. Therefore, suppression of the inflammatory response elicited by activated microglia is considered a potential therapeutic target for neurodegenerative diseases. The cannabinoid (CB) system is widespread in the central nervous system and is very crucial for modulating a spectrum of neurophysiological functions such as pain, appetite, and cognition. In the present study, we synthesized and investigated a novel CB derivative (CD-101) for its ability to suppress lipopolysaccharide (LPS)-mediated activation of BV-2 microglial cells and subsequent release of various inflammatory mediators. CD-101 significantly inhibited the production of inflammatory markers such as nitric oxide, cyclooxygenase-2, and pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1ß, and interleukin-6. The anti-neuroinflammatory effect of this novel cannabinoid derivative occurred by inhibiting p38MAPK phosphorylation and by decreasing nuclear translocation of p65 subunit of nuclear factor kappa-B in LPS-stimulated BV-2 microglial cells. These results suggest that the use of the cannabinoid derivative CD-101 might be a potential therapeutic target against neuroinflammatory disorders.
Assuntos
Canabinoides/farmacologia , Núcleo Celular/metabolismo , Lipopolissacarídeos/farmacologia , Microglia/efeitos dos fármacos , NF-kappa B/metabolismo , Fármacos Neuroprotetores/farmacologia , Pirazóis/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Animais , Canabinoides/síntese química , Canabinoides/uso terapêutico , Linhagem Celular , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Camundongos , Microglia/metabolismo , NF-kappa B/antagonistas & inibidores , Fármacos Neuroprotetores/uso terapêutico , Fosforilação/efeitos dos fármacos , Subunidades Proteicas/metabolismo , Pirazóis/síntese química , Pirazóis/uso terapêutico , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Carbon (C) sequestration capacity in forest ecosystems is generally constrained by soil nitrogen (N) availability. Consequently, N fertilization is seen as a promising tool for enhancing ecosystem-level C sequestration in N-limited forests. We examined the responses of ecosystem C (vegetation and soil) and soil N dynamics to 3 years of annual nitrogen-phosphorus-potassium (N3P4K1 = 11.3 g N, 15.0 g P, 3.7 g K m-2 year-1) or PK fertilization (P4K1), observed over 4 years in a 40-year-old Pinus densiflora forest with poor N nutrition in South Korea. PK fertilization without N was performed to test for PK limitation other than N. Neither tree growth nor soil C fluxes responded to annual NPK or PK fertilization despite an increase in soil mineral N fluxes following NPK fertilization. NPK fertilization increased the rate of N immobilization and 80% of the added N was recovered from mineral soil in the 0-5 cm layer, suggesting that relatively little of the added N was available to trees. These results indicate that N fertilization does not always enhance C sequestration even in forests with poor N nutrition and should therefore be applied with caution.
Assuntos
Desnutrição , Pinus , Ecossistema , Sequestro de Carbono , Florestas , Árvores , Nitrogênio , Solo , FertilizaçãoRESUMO
Free radical production and their targeted action on biomolecules have roles in aging and age-related disorders such as Parkinson's disease (PD). There is an age-associated increase in oxidative damage to the brain, and aging is considered a risk factor for PD. Dopaminergic neurons show linear fallout of 5-10% per decade with aging; however, the rate and intensity of neuronal loss in patients with PD is more marked than that of aging. Here, we enumerate the common link between aging and PD at the cellular level with special reference to oxidative damage caused by free radicals. Oxidative damage includes mitochondrial dysfunction, dopamine auto-oxidation, α-synuclein aggregation, glial cell activation, alterations in calcium signaling, and excess free iron. Moreover, neurons encounter more oxidative stress as a counteracting mechanism with advancing age does not function properly. Alterations in transcriptional activity of various pathways, including nuclear factor erythroid 2-related factor 2, glycogen synthase kinase 3ß, mitogen activated protein kinase, nuclear factor kappa B, and reduced activity of superoxide dismutase, catalase and glutathione with aging might be correlated with the increased incidence of PD.
Assuntos
Envelhecimento/patologia , Encéfalo/patologia , Radicais Livres/metabolismo , Estresse Oxidativo , Doença de Parkinson/patologia , Envelhecimento/metabolismo , Animais , Encéfalo/metabolismo , Humanos , Oxirredução , Doença de Parkinson/metabolismoRESUMO
Parkinson's disease (PD) is a complex multifactorial disease marked by extensive neuropathology in the brain with selective yet prominent and progressive loss of mid-brain dopaminergic neurons. The etiological factors involved in the development of PD are still elusive, but oxidative stress arising when reactive oxygen species (ROS) exceed amounts required for normal redox signaling is considered one of the major factors. ROS cause oxidative damage to proteins, lipids, and DNA and are one of the most prominent factors related to neurodegeneration. Pre-clinical and clinical studies clearly demonstrate the effectiveness of oxidative stress in the pathogenesis of PD. Therefore, regulation of redox signaling and inhibiting excess ROS would contribute greatly not only to extend longevity but also to ameliorate the progression of dopaminergic cell death seen in patients with PD. Several herbal products are beneficial for maintaining nerve cell function and for treating various neurodegenerative disorders by reducing oxidative stress. Here, we summarize the recent knowledge concerning promising herbs that have shown significant beneficial effects based on regulation of redox status and ROS inhibition in toxin-induced PD models.
Assuntos
Sequestradores de Radicais Livres/farmacologia , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/metabolismo , Plantas Medicinais , Animais , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Sequestradores de Radicais Livres/uso terapêutico , Humanos , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Oxirredução , Estresse Oxidativo , Doença de Parkinson/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacosRESUMO
Nutrient enrichment can alleviate productivity limitations and thus substantially increase carbon (C) uptake in northern coniferous forests. Yet, factors controlling stand-to-stand variation of forest ecosystem responses to nutrient enrichment remain unclear. We used five long-term (13 years) nutrient-enrichment experiments across Sweden, where nitrogen (N), phosphorus, and potassium were applied annually to young Norway spruce forests that varied in their baseline ecosystem properties. We measured tree biomass and soil C and N stocks, litterfall C inputs, soil CO2 efflux, and shifts in composition and biomass of soil microbial communities to understand the links between above and belowground responses to nutrient enrichment. We found that the strongest responses in tree biomass occurred when baseline site productivity was lowest. High increases in tree biomass C stocks were generally balanced by weaker responses in organic soil C stocks. The average ecosystem C-N response rate was 35 kg C kg-1 N added, with a nearly five-fold greater response rate in tree biomass than in soil. The positive nutrient enrichment effects on ecosystem C sinks were driven by a 95% increase in tree biomass C stocks, 150% increase in litter production, 67% increase in organic layer C stocks, and a 46% reduction in soil CO2 efflux accompanied by compositional changes in soil microbial communities. Our results show that ecosystem C uptake in spruce forests in northern Europe can be substantially enhanced by nutrient enrichment; however, the strength of the responses and whether the enhancement occurs mainly in tree biomass or soils are dependent on baseline forest productivity.
Assuntos
Sequestro de Carbono , Solo , Biomassa , Carbono , Dióxido de Carbono , Ecossistema , Florestas , Nitrogênio , Nutrientes , Taiga , ÁrvoresRESUMO
Boreal trees are capable of taking up organic nitrogen (N) as effectively as inorganic N. Depending on the abundance of soil N forms, plants may adjust physiological and morphological traits to optimize N uptake. However, the link between these traits and N uptake in response to soil N sources is poorly understood. We examined Pinus sylvestris L. seedlings' biomass growth and allocation, transpiration and N uptake in response to additions of organic N (the amino acid arginine) or inorganic N (ammonium nitrate). We also monitored in situ soil N fluxes in the pots following an addition of N, using a microdialysis system. Supplying organic N resulted in a stable soil N flux, whereas the inorganic N resulted in a sharp increase of nitrate flux followed by a rapid decline, demonstrating a fluctuating N supply and a risk for loss of nitrate from the growth medium. Seedlings supplied with organic N achieved a greater biomass with a higher N content, thus reaching a higher N recovery compared with those supplied inorganic N. In spite of a higher N concentration in organic N seedlings, root-to-shoot ratio and transpiration per unit leaf area were similar to those of inorganic N seedlings. We conclude that enhanced seedlings' nutrition and growth under the organic N source may be attributed to a stable supply of N, owing to a strong retention rate in the soil medium.
Assuntos
Pinus sylvestris , Pinus , Nitrogênio/metabolismo , Pinus/fisiologia , Pinus sylvestris/fisiologia , Raízes de Plantas/fisiologia , Plântula/fisiologia , Solo/química , Árvores/metabolismoRESUMO
Compelling evidence supports the notion that the majority of neurodegenerative diseases are associated with microglia-mediated neuroinflammation. Therefore, quelling of microglial activation may lead to neuronal cell survival. The present study investigated the effects of Kamebakaurin (KMBK), a kaurane diterpene isolated from Isodon japonicus HARA (Labiatae), on the production of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated cytotoxicity in rat primary microglial cultures and the BV-2 cell line. KMBK significantly inhibited the LPS-induced production of nitric oxide (NO) in a concentration-dependent fashion in activated microglial cells. The mRNA and protein levels of inducible nitric oxide synthase (iNOS) and cyclooxycenase-2 (COX-2) were also decreased dose-dependently. Furthermore KMBK inhibited the JNK and p38 mitogen-activated protein kinases (MAPKs) in LPS-stimulated BV-2 microglial cells. Considering the results obtained, the present study authenticated the potential benefits of KMBK as a therapeutic target in ameliorating microglia-mediated neuroinflammatory diseases.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Diterpenos/farmacologia , Isodon/química , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Animais Recém-Nascidos , Linhagem Celular Transformada , Células Cultivadas , Córtex Cerebral/citologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Ativação Enzimática/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Camundongos , Microglia/imunologia , Microglia/patologia , Neurite (Inflamação)/tratamento farmacológico , Neurite (Inflamação)/imunologia , Neurite (Inflamação)/metabolismo , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Substância Negra/citologia , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismoRESUMO
Using panel data from 21 Organization for Economic Cooperation and Development (OECD) countries collected between 2000 and 2016, this study analyzes the effect of age structure on greenhouse gas (GHG) emissions from road transportation. Previous studies have failed to reflect the driver's behavior patterns, especially by age group. We apply the Fully-Modified Ordinary Least Squares (FMOLS) method, including the age structure effect by reorganizing 17 age groups into a polynomial structure. The age structure exhibits an asymmetric inverted U-shaped effect on GHG emissions. Initially, people emit more GHGs as they age, and reach peak emissions in their late 20s, after which emissions fall until around the age of 70, when GHG emissions remain constant because of minimum mobility demand. Factors, such as higher income, increased vehicle ownership, and raised transport volumes increase emission rates. On the other hand, fuel transition and increased fuel price, population density, urbanization rate, and fuel economy reduce GHG emissions. Furthermore, we perform a projection of GHG emissions until 2050, and conclude that the effect of age structure is limited because of the minimum mobility demand of the elderly. We conclude that various policy measures, such as increased fuel economy and urbanization, must be considered in order to achieve sustainable transport.
Assuntos
Gases de Efeito Estufa , Emissões de Veículos , Adolescente , Adulto , Distribuição por Idade , Idoso , Gases de Efeito Estufa/análise , Humanos , Pessoa de Meia-Idade , Organização para a Cooperação e Desenvolvimento Econômico , Meios de Transporte/estatística & dados numéricos , Urbanização , Emissões de Veículos/análise , Adulto JovemRESUMO
The purpose of this article is to empirically find the Environmental Kuznets Curve (EKC) relationship between income and carbon dioxide (CO2) emissions and to analyze the influence of population aging on such emissions. We utilize Korean regional panel data of 16 provinces during the period from 1998 to 2016. To account for the nonstationary time series in the panel, we employ a fully modified ordinary least squares (FMOLS) and estimate long-run elasticity. From the empirical results, we can find the nonlinear relationship between income and CO2 emissions. Additionally, we verify the fact that population aging reduces CO2 emissions. A 1% increase in the proportion of the elderly results in a 0.4% decrease in CO2 emissions. On the other hand, the younger population increases CO2 emissions. These results were in line with those of additional analysis on residential and transportation CO2 emissions, for the robustness check.
Assuntos
Dióxido de Carbono , Desenvolvimento Econômico , Fertilidade , Renda , Idoso , Envelhecimento , Dióxido de Carbono/análise , Monitoramento Ambiental , Humanos , República da CoreiaRESUMO
Trees are able to reduce their carbon (C) losses by refixing some of the CO2 diffusing out of their stems through corticular photosynthesis. Previous studies have shown that under ideal conditions the outflowing CO2 can be completely assimilated in metabolically active, young stem and branch tissues. Fewer studies have, however, been carried out on the older stem sections of large trees and, accordingly, the importance of refixation is still unclear under natural environmental conditions. We investigated the spatial and temporal variation in refixation in ~90-year-old boreal Scots pine (Pinus sylvestris L.) trees by utilizing month-long continuous measurements of stem CO2 efflux (Ec) made at four heights along the bole. Refixation rates were found to vary considerably along the bole, leading to a 28% reduction in long-term Ec in the upper stem compared with a negligible reduction at breast height. This vertical pattern correlated with variation in light availability, bark chlorophyll content and bark type. Analysis of the vertical and diurnal patterns in Ec further suggested that the influence of sap flow on the observed daytime reduction in Ec was small. The areal rates of corticular photosynthesis were much lower than previous estimates of photosynthetic rates per unit leaf area from the same trees, implying that the impact of refixation on tree-scale C uptake was small. However, upscaling of refixation indicated that 23-27% of the potential Ec was refixed by the bole and the branches, thereby significantly reducing the woody tissue C losses. Thus, our results suggest that refixation needs to be considered when evaluating the aboveground C cycling of mature P. sylvestris stands and that breast-height estimates should not be extrapolated to the whole tree.
Assuntos
Dióxido de Carbono/metabolismo , Fotossíntese/fisiologia , Pinus sylvestris/fisiologia , Pinus sylvestris/crescimento & desenvolvimento , Caules de Planta/crescimento & desenvolvimento , Caules de Planta/fisiologiaRESUMO
Manipulating tree belowground carbon (C) transport enables investigation of the ecological and physiological roles of tree roots and their associated mycorrhizal fungi, as well as a range of other soil organisms and processes. Girdling remains the most reliable method for manipulating this flux and it has been used in numerous studies. However, girdling is destructive and irreversible. Belowground C transport is mediated by phloem tissue, pressurized through the high osmotic potential resulting from its high content of soluble sugars. We speculated that phloem transport may be reversibly blocked through the application of an external pressure on tree stems. Thus, we here introduce a technique based on compression of the phloem, which interrupts belowground flow of assimilates, but allows trees to recover when the external pressure is removed. Metal clamps were wrapped around the stems and tightened to achieve a pressure theoretically sufficient to collapse the phloem tissue, thereby aiming to block transport. The compression's performance was tested in two field experiments: a (13)C canopy labelling study conducted on small Scots pine (Pinus sylvestris L.) trees [2-3â m tall, 3-7â cm diameter at breast height (DBH)] and a larger study involving mature pines (â¼15â m tall, 15-25â cm DBH) where stem respiration, phloem and root carbohydrate contents, and soil CO2 efflux were measured. The compression's effectiveness was demonstrated by the successful blockage of (13)C transport. Stem compression doubled stem respiration above treatment, reduced soil CO2 efflux by 34% and reduced phloem sucrose content by 50% compared with control trees. Stem respiration and soil CO2 efflux returned to normal within 3 weeks after pressure release, and (13)C labelling revealed recovery of phloem function the following year. Thus, we show that belowground phloem C transport can be reduced by compression, and we also demonstrate that trees recover after treatment, resuming C transport in the phloem.
Assuntos
Carbono/metabolismo , Floema/metabolismo , Pinus sylvestris/metabolismo , Caules de Planta/metabolismo , Transporte Biológico , Raízes de Plantas/metabolismo , Pressão , Árvores/metabolismoRESUMO
Neuroinflammation is one of the critical pathological mechanisms influencing various neurodegenerative disorders. Most of the neurodegenerative diseases involve over-activation of microglial cells contributing to the demise of neurons. The objective of the current study is to evaluate the anti-inflammatory effect of novel synthetic clovamide derivative on the suppression of microglial activation in an in vitro and in vivo model of neuroinflammation. We have used lipopolysaccharide (LPS) to induce an inflammatory response in murine BV-2 microglial cells. Molecular tools like immunocytochemistry and immunoblotting were used to study the activity of novel synthetic clovamide derivative to inhibit inflammation induced by LPS in microglial cells. In in vivo experiments, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mouse model of neuroinflammation was developed to investigate the anti-neuroinflammatory effects of DPTP [3-(3,4-Dihydroxy-phenyl)-2-[4-(3-trifluoromethylphenyl)-but-2-enoylamino]-propionic acid methyl ester]. DPTP was observed to reduce the proinflammatory response in BV-2 cells induced by LPS. Further investigation revealed that DPTP attenuated phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), which was accompanied by a decrease in nuclear translocation of nuclear factor-κB (NF-κB) in LPS-treated BV2 microglia. Moreover, prophylactic treatment with DPTP (20mg/kg) for 7 days suppressed MPTP induced glial activation and behavioral impairment. Overall, our findings suggested that, DPTP exerts anti-neuroinflammatory effects against activated microglia in an in vitro and in vivo model and hence might be a promising therapeutic agent for alleviating the evolvement of neurodegenerative diseases associated with microglial activation.
Assuntos
Inflamação/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Linhagem Celular , Células Cultivadas , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Inflamação/fisiopatologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/fisiologia , NF-kappa B/metabolismo , Neuroimunomodulação/efeitos dos fármacos , Neuroimunomodulação/fisiologia , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/química , Fosforilação/efeitos dos fármacos , Ratos Sprague-Dawley , Tirosina/análogos & derivados , Tirosina/químicaRESUMO
Acorus species contains diverse pharmacologically active phytochemicals including α-asarone, ß-asarone, and eugenol. We determined if ß-asarone isolated from Acorus gramineus (AG) Solander would be efficacious in protecting BV-2 microglia cells from lipopolysaccharide (LPS)-induced stress signaling. BV-2 microglial cells were pretreated with an AG ethanol extract (1, 10, and 100 µg/mL) or ß-asarone (10, 50, and 100 µM) prior to exposure to LPS (100 ng/mL). AG and ß-asarone inhibited LPS-induced production of nitric oxide in a dose-dependent manner. The mRNA and protein levels of inducible nitric oxide synthase and cyclooxygenase-2 also decreased dose dependently following AG and ß-asarone treatments. Immunostaining and immunoblot studies revealed that ß-asarone also suppressed nuclear factor (NF)-κB activation by blocking IkB degradation. Further mechanistic studies revealed that ß-asarone acted through the JNK/MAPK pathway. Taken together, our findings demonstrate that ß-asarone exhibits anti-inflammatory effects by suppressing the production of pro-inflammatory mediators through NF-κB signaling and the JNK pathways in activated microglial cells and might be developed as a promising candidate to treat various neuroinflammatory diseases.
Assuntos
Anisóis/farmacologia , Lipopolissacarídeos/efeitos adversos , Microglia/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Acorus/química , Derivados de Alilbenzenos , Animais , Anti-Inflamatórios/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Eugenol/farmacologia , Proteínas I-kappa B/genética , Proteínas I-kappa B/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Microglia/metabolismo , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Gastrodia elata Blume (Orchidaceae, GE) a traditional plant in Oriental countries is known for its enormous benefits to treat headaches, dizziness, vertigo and convulsive illnesses. In the present study, the ethnopharmacological role of GE in neuroinflammation mediated by activated microglia and the mechanisms underlying were reported. MATERIALS AND METHODS: BV-2 microglia activated by lipopolysaccharide (LPS) was employed and the effects of GE on corresponding neuroinflammatory parameters were assessed. RESULTS: GE extract inhibited LPS-stimulated production of inflammatory cytokines and down regulated the c-Jun NH(2)-Terminal Kinase (JNK) and nuclear factor-kappa B (NF-κB) signaling pathways, which are known to be involved in neuroinflammation. Further, inhibition of NO and iNOS by 4-hydroxybenzyl alcohol (4-HBA), one of the active constituent of GE in LPS-stimulated BV-2 cells suggest that 4-HBA might be the bioactive candidate. CONCLUSION: GE extract and its active constituent 4-HBA could be further exploited to mitigate microglial activation and may be developed as a new therapeutic remedy in treating various neuroinflammatory diseases.