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Agricultural contamination is a pervasive problem in karst landscapes that negatively impacts groundwater quality, and subsequently harms hydraulically connected springs and associated ecosystems. While most research on agricultural contamination in karst aquifers has focused on nitrate, agricultural operations also alter major ion chemistry in groundwater, which can have significant implications on water rock interactions, geochemical interpretability, and enrichment of harmful contamination. Additionally, recent evidence has questioned the singular role of nutrient enrichment on aquatic ecosystem degradation, thus prompting further investigation into the broader extent of agricultural contamination for improved water quality restoration. In karst aquifers, quantifying the disruption of groundwater quality from agricultural contamination at springs can be challenging as major ions associated with agricultural contamination may be conflated with natural processes and interpretation further compounded by complex flow dynamics. These factors can render traditional statistical methods inadequate for identifying more comprehensive groundwater quality disruptions. To overcome these challenges, we use principal component analysis to classify the major ion covariance signature of agriculturally impaired and unimpaired groundwater and develop a new impairment metric to characterize the relative major ion impairment from agriculture to karst spring water quality. We apply our method to a primarily rural region in northern Florida whereby major ion chemistry has been changing over the last several decades. Our results identify a significant difference in major ion covariance structure between agriculturally impaired and unimpaired groundwater which is exploited to directly link major ion changes at karst springs to agriculture via relating a derived impairment metric to measured nitrate. Our newly developed method is easy to apply and can be used to identify more comprehensive contamination from pollutant sources and prioritize relative water quality restoration.
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This paper makes a contribution to research on digital twins that are generated from robot sensor data. We present the results of an online user study in which 240 participants were tasked to identify real-world objects from robot point cloud data. In the study we manipulated the render style (point clouds vs voxels), render resolution (i.e., density of point clouds and granularity of voxel grids), colour (monochrome vs coloured points/voxels), and motion (no motion vs rotational motion) of the shown objects to measure the impact of these attributes on object recognition performance. A statistical analysis of the study results suggests that there is a three-way interaction between our independent variables. Further analysis suggests: 1) objects are easier to recognise when rendered as point clouds than when rendered as voxels, particularly lower resolution voxels; 2) the effect of colour and motion is affected by how objects are rendered, e.g., utility of colour decreases with resolution for point clouds; 3) an increased resolution of point clouds only leads to an increased object recognition if points are coloured and static; 4) high resolution voxels outperform medium and low resolution voxels in all conditions, but there is little difference between medium and low resolution voxels; 5) motion is unable to improve the performance of voxels at low and medium resolutions, but is able to improve performance for medium and low resolution point clouds. Our results have implications for the design of robot sensor suites and data gathering and transmission protocols when creating digital twins from robot gathered point cloud data.
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Body language is an important aspect of human communication, which an effective human-robot interaction interface should mimic well. Human beings exchange information and convey their thoughts and feelings through gaze, facial expressions, body language, and tone of voice along with spoken words, and infer 65% of the meaning of the communicated messages from these nonverbal cues. Modern robotic platforms are, however, limited in their ability to automatically generate behaviors that align with their speech. In this article, we develop a neural-network-based system that takes audio from a user as an input and generates upper-body gestures, including head, hand, and torso movements of the user on a humanoid robot, namely, Softbank Robotics' Pepper. Our system was evaluated quantitatively as well as qualitatively using Web surveys when driven by natural speech and synthetic speech. We compare the impact of generic and person-specific neural-network models on the quality of synthesized movements. We further investigate the relationships between quantitative and qualitative evaluations and examine how the speaker's personality traits affect the synthesized movements.
Assuntos
Robótica , Expressão Facial , Gestos , Mãos , Humanos , FalaRESUMO
The nuclear ribosomal internal transcribed spacer (ITS) sequences of eight Hypericum species were used to design H. perforatum-specific PCR primers by identification of short "microcode" sequences characteristic of the target species. These were tested with three vouchered H. perforatum DNA samples and eight samples from other species within the Hypericum genus. The most efficient primer combination, FO2 and HRI-S, amplified the genomic DNA from all three H. perforatum samples but not from any of the others apart from H. delphicum. The primer pairing was then tested against seven commercially available ornamental varieties of Hypericum; a positive result was obtained only with the H. perforatum sample. Three consumer products retailed as "St. John's wort" herbal remedies were sampled, two of which gave a positive result for H. perforatum. The assay was sensitive enough to detect 0.75 ng H. perforatum present as just 0.1 % of the total DNA. This method has the potential to be replicated in other plant species and presents a novel use for DNA barcoding data.
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DNA Intergênico , DNA de Plantas , DNA Ribossômico , Contaminação de Medicamentos/prevenção & controle , Hypericum/genética , Qualidade de Produtos para o Consumidor , Primers do DNA , Genes de Plantas , Técnicas de Amplificação de Ácido Nucleico , Reação em Cadeia da Polimerase/métodos , Análise de Sequência de DNARESUMO
Local and traditional knowledge has been the starting point for many successful drug development projects over the last decades. Here we discuss some examples of anti-cancer drugs which have had enormous impact as anti-cancer agents (camptothecan, taxol and derivatives) and a few examples of drugs currently under various stages of preclinical development. Ethnobotanists investigate the relationship between humans and plants in all its complexity, and such research is generally based on a detailed observation and study of the use a society makes of plants. The requirements of modern research on natural products as, for example, outlined in the Convention on Biological Diversity (Rio Convention) and the overall approach in ethnobotanical research are also discussed. Selected phytochemical-pharmacological studies based on traditional plant use are used to highlight the potential of ethnobotany driven anti-cancer research. The link between traditionally used plants and targets of the NF-kappaB pathway is discussed using on an EU-funded, multidisciplinary project as an example. Lastly the potential of chemopreventive agents derived from traditional food plants is briefly addressed.
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Anticarcinógenos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Etnobotânica , Etnofarmacologia , Neoplasias/tratamento farmacológico , Animais , Variação Genética , Humanos , Neoplasias/prevenção & controleRESUMO
Co-verbal gestures are an important part of human communication, improving its efficiency and efficacy for information conveyance. One possible means by which such multi-modal communication might be realized remotely is through the use of a tele-operated humanoid robot avatar. Such avatars have been previously shown to enhance social presence and operator salience. We present a motion tracking based tele-operation system for the NAO robot platform that allows direct transmission of speech and gestures produced by the operator. To assess the capabilities of this system for transmitting multi-modal communication, we have conducted a user study that investigated if robot-produced iconic gestures are comprehensible, and are integrated with speech. Robot performed gesture outcomes were compared directly to those for gestures produced by a human actor, using a within participant experimental design. We show that iconic gestures produced by a tele-operated robot are understood by participants when presented alone, almost as well as when produced by a human. More importantly, we show that gestures are integrated with speech when presented as part of a multi-modal communication equally well for human and robot performances.
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Dietary polyphenols are widely considered to contribute to health benefits in humans. However, little is yet known concerning their bioactive forms in vivo and the mechanisms by which they may contribute toward disease prevention. Although many studies are focusing on the bioavailability of polyphenols through studying their uptake and the excretion of their conjugated forms, few are emphasizing the occurrence of metabolites in vivo formed via degradation by the enzymes of colonic bacteria and subsequent absorption. The purpose of this research was to investigate the relationship between biomarkers of the colonic biotransformation of ingested dietary polyphenols and the absorbed conjugated polyphenols. The results show that the majority of the in vivo forms derive from cleavage products of the action of colonic bacterial enzymes and subsequent metabolism in the liver. Those include the glucuronides of 3-hydroxyphenylacetic, homovanillic, vanillic and isoferulic acid as well as 3-(3-methoxy-4-hydroxyphenyl)-propionic, 3-(3-hydroxyphenyl)-propionic acid, and 3-hydroxyhippuric acid. In contrast, intact conjugated polyphenols themselves, such as the glucuronides of quercetin, naringenin and ferulic, p-coumaric, and sinapic acid were detected at much lower levels. The results suggest that consideration should be given to the cleavage products as having a putative role as physiologically relevant bioactive components in vivo.
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Dieta , Flavonoides , Fígado/metabolismo , Fenóis/metabolismo , Polímeros/metabolismo , Adulto , Disponibilidade Biológica , Biotransformação , Cromatografia Líquida de Alta Pressão , Feminino , Glucuronídeos/metabolismo , Humanos , Absorção Intestinal , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , PolifenóisRESUMO
We have investigated the ionophoretic and apoptotic properties of the daucane sesquiterpene ferutinin and three related compounds, ferutidin, 2-alpha-hydroxyferutidin and teferin, all isolated from various species of plants from the genus Ferula. Ferutinin induced a biphasic elevation of intracellular Ca2+ in the leukemia T-cell line, Jurkat. First, a rapid calcium peak was observed and inhibited by BAPTA-AM. This initial calcium mobilization was followed by a sustained elevation, mediated by the entry of extracellular calcium through L-type calcium channels and sensitive to inhibition by EGTA. Moreover, ferutinin-induced apoptosis in Jurkat cells, and this event was preceded, in a cyclosporine-A sensitive manner, by a loss of mitochondrial transmembrane potential (DeltaPsim) and by an increase in intracellular reactive oxygen species. Ferutinin-induced DNA fragmentation was mediated by a caspase-3-dependent pathway, and was initiated independently of any specific phase of the cell cycle. The evaluation of ferutinin analogs in calcium mobilization and apoptosis assays showed strict structure-activity relationships, with p-hydroxylation of the benzoyl moiety being requested for activity.
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Apoptose , Benzoatos/farmacologia , Cálcio/metabolismo , Compostos Bicíclicos com Pontes , Caspase 3 , Caspases/metabolismo , Linhagem Celular , Cicloeptanos , Humanos , Células Jurkat , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos , Células Tumorais CultivadasRESUMO
The use of plant extracts to alleviate inflammatory diseases is centuries old and continues to this day. This review assesses the current understanding of the use of such plants and natural products isolated from them in terms of their action against the ubiquitous transcription factor, nuclear factor kappa B (NF-kappaB). As an activator of many pro-inflammatory cytokines and inflammatory processes the modulation of the NF-kappaB transduction pathway is a principal target to alleviate the symptoms of such diseases as arthritis, inflammatory bowel disease and asthma. Two pathways of NF-kappaB activation will first be summarised, leading to the IKK (IkappaB kinase) complex, that subsequently initiates phosphorylation of the NF-kappaB inhibitory protein (IKB). Natural products and some extracts are reviewed and assessed for their activity and potency as NF-kappaB inhibitors. A large number of compounds are currently known as NF-kappaB modulators and include the isoprenoids, most notably kaurene diterpenoids and members of the sesquiterpene lactones class, several phenolics including curcumin and flavonoids such as silybin. Additional data on cellular toxicity are also highlighted as an exclusion principle for pursuing such compounds in clinical development. In addition, where enough data exists some conclusions on structure-activity relationship are provided.
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Produtos Biológicos/farmacologia , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Animais , Produtos Biológicos/química , Diterpenos/química , Fungos/química , Humanos , Quinase I-kappa B , Proteínas I-kappa B/efeitos dos fármacos , Proteínas I-kappa B/metabolismo , Estrutura Molecular , NF-kappa B/efeitos dos fármacos , Fenóis/química , Fosforilação , Extratos Vegetais/química , Poríferos/química , Proteínas Serina-Treonina Quinases/metabolismo , Sesquiterpenos/química , Relação Estrutura-Atividade , Terpenos/química , Triterpenos/química , Ubiquitinas/metabolismoRESUMO
Reliable methods to identify medicinal plant material are becoming more important in an increasingly regulated market place. DNA-based methods have been recognised as a valuable tool in this area with benefits such as being unaffected by the age of the plant material, growth conditions and harvesting techniques. It is possible that the methods of production used for medicinal plant products will degrade or remove DNA. So how applicable are these techniques to processed medicinal plant products? A simple PCR-based identification technique has been developed for St. John's Wort, Hypericum perforatum L. Thirteen St. John's Wort products were purchased including capsules, tablets and tinctures. DNA was extracted from each product, and the species specific PCR test conducted. DNA was successfully extracted from all thirteen products, using a fast and efficient modified method for extracting DNA from tinctures. Only four products yielded the full length ITS region (850 bp) due to the quality of the DNA. All of the products tested positive for H. perforatum DNA. DNA-based identification methods can complement existing methods of authentication. This paper shows that these methods are applicable to a wide range of processed products, provided that they are designed to account for the possibility of DNA degradation.
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DNA de Plantas , Medicina Herbária/métodos , Hypericum/genética , Medicamentos sem Prescrição/análise , Extratos Vegetais/análise , Plantas Medicinais/genética , Reação em Cadeia da Polimerase/métodos , Humanos , FitoterapiaRESUMO
BACKGROUND: An efficient method for the identification of medicinal plant products is now a priority as the global demand increases. This study aims to develop a DNA-based method for the identification and authentication of plant species that can be implemented in the industry to aid compliance with regulations, based upon the economically important Hypericum perforatum L. (St John's Wort or Guan ye Lian Qiao). METHODS: The ITS regions of several Hypericum species were analysed to identify the most divergent regions and PCR primers were designed to anneal specifically to these regions in the different Hypericum species. Candidate primers were selected such that the amplicon produced by each species-specific reaction differed in size. The use of fluorescently labelled primers enabled these products to be resolved by capillary electrophoresis. RESULTS: Four closely related Hypericum species were detected simultaneously and independently in one reaction. Each species could be identified individually and in any combination. The introduction of three more closely related species to the test had no effect on the results. Highly processed commercial plant material was identified, despite the potential complications of DNA degradation in such samples. CONCLUSION: This technique can detect the presence of an expected plant material and adulterant materials in one reaction. The method could be simply applied to other medicinal plants and their problem adulterants.
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Valeriana officinalis (Valerianaceae) has been of great interest for its therapeutic uses for treating mild nervous tension and temporary sleeping problems. In traditional European medicine it has been also reported as an antiinflammatory remedy. This study reports that the EtOAc extract of the underground parts of V. officinalis showed inhibitory activity against NF-kappaB at 100 microg/mL in the IL-6/Luc assay on HeLa cells and provided protection against excitotoxicity in primary brain cell cultures at micromolar concentrations. Bioassay-guided fractionation of the EtOAc extract led to the isolation of three known sesquiterpenes: acetylvalerenolic acid (1), valerenal (2) and valerenic acid (3), 1 and 3 were active as inhibitors of NF-kappaB at a concentration of 100 microg/mL. Acetylvalerenolic acid (1) reduced NF-kappaB activity to 4%, whereas valerenic acid (3) reduced NF-kappaB activity to 25%.
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NF-kappa B/antagonistas & inibidores , Extratos Vegetais/farmacologia , Valeriana/química , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Técnicas de Cocultura , Células HeLa , Humanos , Ácido Caínico/antagonistas & inibidores , N-Metilaspartato/antagonistas & inibidores , Neurônios/citologia , Neurônios/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificaçãoRESUMO
Crude extracts of Witheringia solanacea leaves showed inhibition of NF-kappaB activation at 100 microg/mL induced by phorbol 12-myristate-13-acetate (PMA) in HeLa cells stably transfected with a luciferase reporter gene controlled by the IL-6 promoter. Three physalins were isolated from an active fraction, namely, physalins B (1), F (2), and D (3). Of these compounds, 1 and 2 demonstrated inhibitory activities on PMA-induced NF-kappaB activation at 16 and 8 microM and induced apoptosis after 24 h in a cell-cycle analysis using a human T cell leukemia Jurkat cell line. Compound 2 also inhibited TNF-alpha-induced NF-kappaB activation at 5 microM through the canonical pathway, but was inactive in the Tet-On-Luc assay, indicating specificity of action, although it interfered with Tet-On-Luc at higher concentrations. It is suggested that the presence of a double bond and an epoxy ring between carbons 5 and 6 in compounds 1 and 2, respectively (which are not present in compound 3), are related to their anti-inflammatory activity.
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Anti-Inflamatórios/isolamento & purificação , Lactonas/isolamento & purificação , NF-kappa B/antagonistas & inibidores , Plantas Medicinais/química , Solanaceae/química , Esteroides/isolamento & purificação , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Células HeLa/efeitos dos fármacos , Humanos , Interleucina-6/genética , Células Jurkat/efeitos dos fármacos , Lactonas/química , Lactonas/farmacologia , Luciferases/genética , Luciferases/metabolismo , Estrutura Molecular , NF-kappa B/metabolismo , Panamá , Folhas de Planta/química , Secoesteroides , Esteroides/química , Esteroides/farmacologia , Acetato de Tetradecanoilforbol/farmacologia , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
Four guaianolide type sesquiterpene lactones (SL), namely the new 1,2-dihydro-3-oxo-costic acid guaianyl ester 3beta-O-(1,2-didehydro-3-oxo-costoyloxy)-4beta,10beta-dihydroxy-guaia-1(2)-en-6beta,12-olide (1) and 3beta-O-(1,2-didehydro-3-oxo-costoyloxy)-4beta,10beta-dihydroxy-guaia-1(2)-en-6alpha,12-olide (2), as well as the known moroccolide A [5alphaH-2beta,4-epoxy-3beta-hydroxy-guaia-1(10),11(13)-dien-6beta,12-olide, 3] and 3beta-O-(2-methylbutyryl)-moroccolide A [5alphaH-2beta,4-epoxy-3beta-(2-methylbutyryloxy)-guaia-1(10),11(13)-dien-6beta,12-olide, 4] were examined for their cytotoxic and anti-inflammatory effects in HeLa, Jurkat T and human peripheral blood mononuclear cells. Compounds 1, 2 and 4 were found to exert a strong cytotoxicity similar in potency in all investigated cell types, whereas 3 was significantly less active. Along with the cytotoxic effect compounds 1 and 4 showed a potent and comparable down-regulation of the mRNAs of the house-keeping genes beta-actin and GAP-DH in PBMCs after 20 h. In contrast, the down-regulation of the PMA-induced mRNA levels of the NF-kappaB-driven pro-inflammatory genes IL-2, IL-6, GM-CSF, TNF-alpha, and IL-1beta in PBMCs is significantly stronger with compound 4. Compound 3 did not significantly modulate cytokine mRNAs levels at biochemically relevant concentrations. The electromobility shift assay (EMSA), revealed a stronger inhibition of NF-kappaB for 1 (IC(50) 2.5 microM) than for 4 (IC(50) 5 microM). Both compounds were also subjected to an IL-6 luciferase reporter gene assay and showed IC(50) values of 1.0 (1) and 1.2 microM (4). Thus, the NF-kappaB inhibition measured by EMSA, as well as the IL-6 luciferase assay did not reflect the differential modulation of pro-inflammatory genes measured with RT-rt-PCR.
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Anti-Inflamatórios/farmacologia , Lactonas/farmacologia , Sesquiterpenos de Guaiano/farmacologia , Animais , Linhagem Celular Tumoral , Citocinas/metabolismo , Regulação para Baixo , Células HeLa , Humanos , Células Jurkat , Lactonas/toxicidade , Leucócitos Mononucleares/efeitos dos fármacos , RNA Mensageiro/metabolismo , Sesquiterpenos de Guaiano/toxicidadeRESUMO
Six biflavonoid and related compounds were isolated from the ethanolic extract of Ochna macrocalyx bark. One is a new compound, the isoflavanone dimer dehydroxyhexaspermone C ( 1). Previously isolated compounds obtained from the bark are biisoflavonoid hexaspermone C ( 2). tetrahydrofuran derivative ochnone ( 3). furobenzopyran derivative cordigol ( 4). and biflavonoids calodenin B ( 5). and dihydrocalodenin B ( 6). Although 3 has already been isolated, its spectral data are presented here for the first time. Isolated compounds were tested for cytotoxic activity on MCF-7 breast cancer cells using the MTT reduction assay method. Compound 5 showed cytotoxic activity (7 +/- 0.5 microM) and 6 showed moderate cytotoxicity (35 +/- 7 microM). In antibacterial assays performed using three strains of multi-drug resistant (mdr) Staphylococcus aureus (RN4220, XU212 and SA-1199-B) compounds 5 and in particular 6 showed strong antibacterial activity (MICs 5 : 64, 8, 16 microg/mL 6 : 8, 8, 8 microg/mL, respectively). The ethanolic extract of the bark also showed NF-kappaB inhibitory activity.
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Antibacterianos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Flavonoides/farmacologia , Malpighiaceae , Fitoterapia , Extratos Vegetais/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Resistência a Múltiplos Medicamentos , Flavonoides/química , Humanos , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , NF-kappa B/antagonistas & inibidores , Casca de Planta , Extratos Vegetais/química , Staphylococcus aureus/efeitos dos fármacos , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
Fractionation of extracts of the leaves of Melicope borbonica (syn. Euodia borbonica var. borbonica), a medicinal plant from the Réunion Island that is traditionally used for wound healing and other ailments, afforded an acetophenone (xanthoxylin) and two coumarins, scoparone and limettin, as the major constituents. All three compounds exhibited moderate antifungal activity against Candida albicans and Penicillium expansum, in accordance with the traditional use of the plant. Moreover, 2,4,6-trimethoxyacetophenone (methylxanthoxylin), three other coumarins [7-(3-methyl-2-butenyloxy)-6-methoxycoumarin, cedrelopsin and psoralen], two sesquiterpenes (alpha-curcumene and 3,6-epidioxy-1,10-bisaboladiene), eugenol, methyleugenol and a lignan (sesamin) were isolated. None of the isolated constituents exhibited antiin fl ammatory activity in vitro. No alkaloids were detected.
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Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Penicillium/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/farmacologia , Rutaceae , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Humanos , Testes de Sensibilidade Microbiana , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Folhas de Planta , Cicatrização/efeitos dos fármacosRESUMO
In our ongoing research into anti-inflammatory compounds from medicinal plants in the Mediterranean area, we have isolated several furanocoumarins from the roots of Oppopanax chironium (L.), and have evaluated them for activity related to T-cell functionality. Heraclenin (1) and imperatorin (2) significantly inhibited T cell receptor-mediated proliferation in human primary T cells in a concentration-dependent manner. In transient transfection experiments with a plasmid containing the IL-2 promoter we found that imperatorin is a potent inhibitor of IL-2 gene transcription. To further characterize the inhibitory mechanisms of imperatorin at the transcriptional level, we examined the DNA-binding and transcriptional activities of NF-kappaB, NFAT, and AP-1 transcription factors in Jurkat T cells. We found that imperatorin inhibited both the NFAT binding to DNA and transcriptional activities, without affecting significantly the activation of the NF-kappaB and AP-1 transcription factors. These findings provide new insights into the molecular mechanisms involved in the immunomodulatory and anti-inflammatory activities of natural furanocoumarins.
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Anti-Inflamatórios não Esteroides/farmacologia , Apiaceae , Proliferação de Células/efeitos dos fármacos , Proteínas de Ligação a DNA/efeitos dos fármacos , Furocumarinas/farmacologia , Proteínas Nucleares/efeitos dos fármacos , Fitoterapia , Linfócitos T/efeitos dos fármacos , Fatores de Transcrição/efeitos dos fármacos , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Relação Dose-Resposta a Droga , Furocumarinas/administração & dosagem , Furocumarinas/uso terapêutico , Humanos , Células Jurkat/efeitos dos fármacos , Leucócitos Mononucleares/efeitos dos fármacos , Fatores de Transcrição NFATC , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Raízes de PlantasRESUMO
Opopanax chironium is a rich source of furano- and dihydrofuranocoumarins, whose accumulation in all plant parts and especially the roots is presumably responsible for the poisonous properties of the species. The presence of two distinct chemotypes was evidenced, with the one from Sicily affording the new dihydrofuranocoumarins 5d and 5e, while extracts from the Sardinian chemotype showed powerful apoptotic activity, which was traced to the prenylated furanocoumarins heraclenin (2a) and imperatorin (2b). Despite a close structural similarity, compounds 2a and 2b induced apoptosis in Jurkat leukemia cells in mechanistically different ways.