RESUMO
Fruit traits have historically been interpreted as plant adaptations to their seed dispersers. On the other hand, different environmental factors, which vary spatially and temporally, can shape fruit-trait variation. The mistletoe Tristerix corymbosus has a latitudinal distribution along the South American Pacific rim that encompasses two different biomes, the matorral of central Chile and the temperate forest that extends south of the matorral. This mistletoe shows contrasting fruiting phenology (spring vs summer), fruit color (yellow vs green), and seed dispersers (birds vs marsupial) in these two biomes. We characterized geographic variation of morphological and nutritional fruit traits of T. corymbosus to evaluate which macroecological factor, biome or latitude, better explains spatial variation in these variables. For each of 22 populations, we obtained environmental data (temperature, precipitation, and canopy cover), measured fruit and seed morphology traits (size, shape, and weight), and pulp moisture and nutritional content (fiber, protein, fat, carbohydrates, ash, and caloric content). Patterns of variation for each variable were described by fitting and comparing five different simple models varying in slope, intercept or both. Fruit morphology showed a clear biome-related disruptive pattern, seed morphological traits were unrelated to either biome or latitude, whereas nutritional variables showed diverse patterns. Different environmental factors seem to affect fruit development and phenology, determining the observed fruit characteristics, with seed dispersers playing a minor role in shaping these patterns. More generally, the contrasting plant-seed disperser associations we addressed can be interpreted as the outcome of an ecological-fitting rather than of a coevolutionary process.
Assuntos
Marsupiais , Erva-de-Passarinho , Phoradendron , Animais , Frutas , Fenótipo , SementesRESUMO
Current antineoplastic agents present multiple disadvantages, driving an ongoing search for new and better compounds. Four lupane-type triterpenes, 3α,24-dihydroxylup-20(29)-en-28-oic acid (1), 3α,23-dihydroxy-30-oxo-lup-20(29)-en-28-oic acid (2), 3α,23-O-isopropylidenyl-3α,23-dihydroxylup-20(29)-en-28-oic acid (3), and 3α,23-dihydroxylup-20(29)-en-28-oic acid (4), previously isolated from Phoradendron wattii, were evaluated on two cell lines of chronic (K562) and acute (HL60) myeloid leukemia. Compounds 1, 2, and 4 decreased cell viability and inhibit proliferation, mainly in K562, and exhibited an apoptotic effect from 24 h of treatment. Of particular interest is compound 2, which caused arrest in active phases (G2/M) of the cell cycle, as shown by in silico study of the CDK1/Cyclin B/Csk2 complex by molecular docking. This compound [3α,23-dihydroxy-30-oxo-lup-20(29)-en-28-oic acid] s a promising candidate for incorporation into cancer treatments and deserves further study.
Assuntos
Leucemia , Phoradendron , Triterpenos , Ciclo Celular , Linhagem Celular , Humanos , Leucemia/tratamento farmacológico , Simulação de Acoplamento Molecular , Estrutura Molecular , Phoradendron/metabolismo , Folhas de Planta/metabolismoRESUMO
Ligaria cuneifolia (Ruiz & Pav.) Tiegh (Loranthaceae) and Phoradendron liga (Gillies ex Hook. & Arn.) Eichler (Santalaceae) are regarded as Argentine mistletoes based on their similarities with the European counterpart, Viscum album L. (Santalaceae). These two species are the most used medicinal plants to treat high blood pressure in the Argentinian population. To provide scientific grounds to their traditional use and therapeutic potential, they were selected as herbal drug candidates. The main findings would support the anti-hypertensive action, the anticholesterolemic and antioxidant features of L.â cuneifolia, and immunomodulatory properties for both species. Quercetin-O-glycosides, galloyl glycosides, and proanthocyanidins are present in L.â cuneifolia while P.â liga shows C-glycosyl flavones and 3-deoxyproanthocyanidins. This review summarizes the phytochemical characterization, medicinal properties and reveals promising results warranting future efforts for further investigation.
Assuntos
Flavonas , Loranthaceae , Phoradendron , Proantocianidinas , Santalaceae , Loranthaceae/química , Quercetina , Antioxidantes/farmacologia , Anti-Hipertensivos , Extratos Vegetais/química , Glicosídeos/farmacologiaRESUMO
Plant-derived secondary metabolites are a source of promising bioactive molecules in the search for safer more selective cancer drugs. Mexico's flora is extremely diverse and many species, such as Phoradendron wattii, form part of traditional medicine. Compounds with notable cytotoxic activity have been isolated from P. wattii, but their concentrations may vary seasonally. The aim was to identify any variation in active metabolite concentrations in Phoradendron wattii methanol extracts in response to season. Betulin exhibited the most evident seasonal variations, being most abundant during the midsummer drought. Cytotoxic activity was highest (29 ± 1 µg/mL) in the rainy season methanol extract. Though not the most abundant metabolite in the extracts, 3α,24-dihydroxylup-20(29)-en-28-oic acid is apparently one of the most active among them and is a promising chemotaxonomic biomarker for this species. In summary, secondary metabolite concentrations in P. wattii methanol extracts varied in response to season, and these variations influenced cytotoxic activity.
Assuntos
Antineoplásicos , Phoradendron , Antineoplásicos/farmacologia , Metanol , Extratos Vegetais/farmacologia , Estações do AnoRESUMO
Intraspecific competition among parasites should, in theory, increase virulence, but we lack clear evidence of this from nature.1-3 Parasitic plants, which are sessile and acquire carbon-based resources through both autotrophy (photosynthesis) and heterotrophy (obtaining carbon from the host), provide a unique opportunity to experimentally study the role of intraspecific competition for nutrients in shaping the biology of both parasite and host.4-6 Here, we manipulated the spatial position of naturally occurring individuals of desert mistletoe (Phoradendron californicum), a xylem hemiparasite, by removing parasites from co-infected branches of a common nitrogen-fixing host, velvet mesquite (Prosopsis velutina), in the Sonoran Desert. We measured physiological performance of both host and parasite individuals under differing competitive environments-parasite location along the xylem stream-through time. Performance was determined by measuring resource availability and use, given that resource demand changed with competitor removal and monsoon-driven amelioration of seasonal drought. Our principal finding was that intraspecific competition exists for xylem resources between mistletoe individuals, including host carbon. Host performance and seasonal climate variation altered the strength of competition and virulence. Hemiparasitic desert mistletoes demonstrated high heterotrophy, yet experimental removals revealed density- and location-dependent effects on the host through feedbacks that reduced mistletoe autotrophy and improved resource availability for the remaining mistletoe individual. Trophic flexibility tempered intraspecific competition for resources and reduced virulence. Mistletoe co-infections might therefore attenuate virulence to maintain access to resources in particularly stressful ecological environments. In summary, experimental field manipulations revealed evidence for intraspecific competition in a parasite species.
Assuntos
Fabaceae/fisiologia , Phoradendron/parasitologia , Processos Autotróficos , Carbono , Clima , Interações Hospedeiro-Parasita , Nitrogênio , Estações do AnoRESUMO
The present study aimed to investigate the reciprocal effects of Phoradendron perrottetii (mistletoe) and T. guianensis (host plant) regarding their polyphenol composition. Taking into account that tannins are important molecules in plant defense and their biosynthesis tends to be enhanced when a species is exposed to stress, we address the following questions: (1) Are the tannins found in our model species important in the interaction between host and mistletoe? (2) Does the presence of mistletoe induce changes in the content of tannins and other polyphenols in the host plant? (3) Do we find differences between the tannin sub-groups in the responses of the host plant to mistletoe? (4) Could the observed differences reflect the relative importance of one tannin group over another as chemical defense against the mistletoe? Using a polyphenol and tannin group-specific MRM methods we quantified four different tannin sub-groups together with flavonoid and quinic acid derivatives by ultra-performance liquid chromatography tandem mass spectrometry together with the oxidative and protein precipitation activities of leaves and branches of Tapirira guianensis and Phoradendron perrottetii. We selected leaves and branches of six non-parasitized trees of T. guianensis. Leaves and branches of nine individuals of T. guianensis parasitized by P. perrottetii were also sampled. For each parasitized tree, we sampled an infested branch and its leaves, as well as a non-infested branch and its leaves. Infested branches were divided into three groups: gall (the host-parasite interface), proximal, and distal region. Both proanthocyanidins and ellagitanins seem to be important for plant-plant parasitism interaction: host infested tissues (gall and surrounding regions) have clearly less tannin contents than healthy tissues. Mistletoe showed high levels of quinic acid derivatives and flavonoids that could be important during hastorium formation and intrusion on host tissues, suggesting a defense mechanism that could promote oxidative stress together with an inhibition of mistletoe seed germination, consequently avoiding secondary infestations. Polyphenol detected in T. guianensis-P. perrottetii interaction could play different role as plant-mistletoe strategies of survival.
Assuntos
Anacardiaceae/parasitologia , Interações Hospedeiro-Parasita , Phoradendron/metabolismo , Polifenóis/metabolismo , Anacardiaceae/metabolismo , Flavonoides/metabolismo , Interações Hospedeiro-Parasita/fisiologia , Taninos Hidrolisáveis/metabolismo , Proantocianidinas/metabolismo , Ácido Quínico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Taninos/metabolismoRESUMO
Mistletoes are a widespread group of plants often considered to be hemiparasitic, having detrimental effects on growth and survival of their hosts. We studied the effects of the Pacific mistletoe, Phoradendron villosum, a member of a largely autotrophic genus, on three species of deciduous California oaks. We found no effects of mistletoe presence on radial growth or survivorship and detected a significant positive relationship between mistletoe and acorn production. This latter result is potentially explained by the tendency of P. villosum to be present on larger trees growing in nitrogen-rich soils or, alternatively, by a preference for healthy, acorn-producing trees by birds that potentially disperse mistletoe. Our results indicate that the negative consequences of Phoradendron presence on their hosts are negligible-this species resembles an epiphyte more than a parasite-and outweighed by the important ecosystem services mistletoe provides.
Assuntos
Phoradendron/fisiologia , Quercus/fisiologia , California , Ecossistema , Quercus/crescimento & desenvolvimento , Dispersão de SementesRESUMO
Three new lupane-type triterpenes, 3α,24-dihydroxylup-20(29)-en-28-oic acid (1), 3α,23-dihydroxy-30-oxolup-20(29)-en-28-oic acid (2), and 3α,23-O-isopropylidenyl-3α,23-dihydroxylup-20(29)-en-28-oic acid (3), together with eight known compounds (4-11) were isolated from a methanol extract of Phoradendron vernicosum aerial parts. The chemical structures of 1-3 were determined on the basis of spectroscopic data interpretation. The isolated compounds were tested against seven human cancer cell lines and two normal cell lines.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Phoradendron/química , Componentes Aéreos da Planta/química , Triterpenos/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Células KB , Células MCF-7 , México , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Extratos Vegetais/química , Folhas de Planta/química , Triterpenos/química , Triterpenos/farmacologiaRESUMO
Phoradendron mucronatum and P. microphyllum are plants that found in tropical and subtropical areas, used in traditional medicine and popularly known as mistle-thrush. The aim of this study was to identify the chemical constituents of different leaf extracts from P. mucronatum and P. microphyllum and assess cytotoxic activity against strains from a human tumour cells. Extracts obtained with hexane, dichloromethane, chloroform and ethyl acetate from the leaves were analysed by gas chromatography coupled with mass spectrometry (GC-MS) and the cytotoxicity was assessed by the MTT method (bromide (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)). The tested human tumour cells were NCI-H292 (human pulmonar mucoepidermoid carcinoma), MCF-7 (human breast adenocarcinoma) and HEp-2 (epidermoid carcinoma of the larynx). Analysis by GC/MS of the extracts from leaves of P. microphyllum and P. mucronatum detected 51 different compounds, such as alkaloids, diterpenes, triterpenes, sterols, alcohols, aldehydes, fatty acids and hydrocarbons. In the cytotoxic evaluation, hexane and ethyl acetate extracts from the leaves P. microphyllum inhibited cell growth of NCI-H292 strains (72.97%) and HEp-2 (87.53%), respectively. The extracts of P. mucronatum species showed an inhibitory effect towards NCI-H292 (83.19%/hexane), MCF-7 (88.69%/dichloromethane) and HEp-2 (93.40%/hexane). The extracts showed cytotoxic activity against the tested strains, especially the P. mucronatum, which presented the highest percentages of inhibition of cell growth.
Assuntos
Phoradendron/química , Extratos Vegetais/química , Folhas de Planta/química , Viscaceae/química , Acetatos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Clorofórmio/química , Cromatografia Gasosa-Espectrometria de Massas , Hexanos/química , Humanos , Células MCF-7 , Cloreto de Metileno/química , Extratos Vegetais/farmacologia , Reprodutibilidade dos Testes , Sais de Tetrazólio , Tiazóis , Testes de ToxicidadeRESUMO
ABSTRACT Phoradendron mucronatum and P. microphyllum are plants that found in tropical and subtropical areas, used in traditional medicine and popularly known as mistle-thrush. The aim of this study was to identify the chemical constituents of different leaf extracts from P. mucronatum and P. microphyllum and assess cytotoxic activity against strains from a human tumour cells. Extracts obtained with hexane, dichloromethane, chloroform and ethyl acetate from the leaves were analysed by gas chromatography coupled with mass spectrometry (GC-MS) and the cytotoxicity was assessed by the MTT method (bromide (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)). The tested human tumour cells were NCI-H292 (human pulmonar mucoepidermoid carcinoma), MCF-7 (human breast adenocarcinoma) and HEp-2 (epidermoid carcinoma of the larynx). Analysis by GC/MS of the extracts from leaves of P. microphyllum and P. mucronatum detected 51 different compounds, such as alkaloids, diterpenes, triterpenes, sterols, alcohols, aldehydes, fatty acids and hydrocarbons. In the cytotoxic evaluation, hexane and ethyl acetate extracts from the leaves P. microphyllum inhibited cell growth of NCI-H292 strains (72.97%) and HEp-2 (87.53%), respectively. The extracts of P. mucronatum species showed an inhibitory effect towards NCI-H292 (83.19%/hexane), MCF-7 (88.69%/dichloromethane) and HEp-2 (93.40%/hexane). The extracts showed cytotoxic activity against the tested strains, especially the P. mucronatum, which presented the highest percentages of inhibition of cell growth.
Assuntos
Humanos , Extratos Vegetais/química , Folhas de Planta/química , Viscaceae/química , Phoradendron/química , Sais de Tetrazólio , Tiazóis , Extratos Vegetais/farmacologia , Clorofórmio/química , Reprodutibilidade dos Testes , Testes de Toxicidade , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células MCF-7 , Hexanos/química , Cromatografia Gasosa-Espectrometria de Massas , Cloreto de Metileno/química , Acetatos/químicaRESUMO
UNLABELLED: ⢠PREMISE OF THE STUDY: A recurrent explanation for phylogeographic discontinuities in the Baja California Peninsula and the Sonoran Desert Region has been the association of vicariant events with Pliocene and Pleistocene seaway breaks. Nevertheless, despite its relevance for plant dispersal, other explanations such as ecological and paleoclimatic factors have received little attention. Here, we analyzed the role of several of these factors to describe the phylogeographic patterns of the desert mistletoe, Phoradendron californicum.⢠METHODS: Using noncoding chloroplast regions, we assess the marginal probability of 19 a priori hypotheses related to geological and ecological factors to predict the cpDNA variation in P. californicum using a Bayesian coalescent framework. Complementarily, we used the macrofossil record and niche model projections on Last Glacial Maximum climatic conditions for hosts, mistletoe, and a bird specialist to interpret phylogeographic patterns.⢠KEY RESULTS: Genealogical reconstructions revealed five clades, which suggest a combination of cryptic divergence, long-distance seed dispersal, and isolating postdivergence events. Bayesian hypothesis test favored a series of Pliocene and Pleistocene geological events related to the formation of the Baja California Peninsula and seaways across the peninsula as the most supported explanation for this genealogical pattern. However, age estimates, niche projections, and fossil records show dynamic host-mistletoe interactions and evidence of host races, indicating that ecological and geological factors have been interacting during the formation and structuring of phylogeographic divergence.⢠CONCLUSIONS: Variation in cpDNA across the species range results from the interplay of vicariant events, past climatic oscillations, and more dynamic factors related to ecological processes at finer temporal and spatial scales.
Assuntos
DNA de Cloroplastos/genética , Phoradendron/genética , Teorema de Bayes , Clima , Ecossistema , Evolução Molecular , México , Dados de Sequência Molecular , Filogenia , Filogeografia , Análise de Sequência de DNA , Sudoeste dos Estados UnidosRESUMO
Resumen: El "ka'avotyre'y", Phoradendron obtusissimum (V iscaceae), es una especie empleada con fines medicinales en Paraguay para tratar enfermedades hepáticas. El presente trabajo se desarrolló dentro del marco del proyecto "Conservación, fortalecimiento y uso sostenible de la flora de Itá Azul y San Gervasio, Colonia Independencia, Reserva de Recursos Manejados Ybytyruzu, Paraguay" y tuvo por objetivo describir la morfoanatomía de P . obtusissimum. Los caracteres diferenciales son: estomas paracíticos en ambas epidermis, índice estomático en epidermis adaxial (5,71)-6,62-(8,33) y en epidermis abaxial (6,45)-1 1,20-(14,29); presencia de drusas en todo el mesófilo. Se presentan así elementos de diagnóstico útiles a la hora de identificar a la especie estudiada. Palabras clave: Phoradendron obtusissimum, morfoanatomía, planta medicinal.
Assuntos
Plantas Medicinais/anatomia & histologia , Viscaceae/anatomia & histologia , Phoradendron/anatomia & histologia , Medicina Tradicional , Paraguai , Hepatopatias/tratamento farmacológicoRESUMO
Phoradendron bathyoryctum Eichler (Viscaceae) es una planta hemiparásita que crece en la República Argentina sobre varias especies arbóreas. Se utiliza en medicina popular de la misma manera que el muérdago europeo (Viscum album L. Viscaceae), para disminuir la presión arterial. Los muérdagos, a veces, pueden ser susceptibles de epiparasitismo, o también sufrir el ataque de diferentes agentes fitopatógenos. El objetivo de este estudio es analizar los cambios anatómicos que se producen en las hojas de Ph. bathyoryctum cuando son afectadas por algún agente infeccioso. Se colectaron ejemplares sanos e infectados, los últimos, con lesiones foliares superficiales. Se realizaron técnicas de raspado, diafanizado y obtención de epidermis en las hojas de los ejemplares. También se practicaron reacciones histoquímicas. En las hojas infectadas se observó una destrucción progresiva de los estomas y cambios en el resto de los tejidos epidérmico y subepidérmico, que dieron como resultado la formación de estructuras visibles macroscópicamente, y semejantes a lenticelas foliares. De acuerdo con las observaciones realizadas y por comparación con la bibliografía consultada, se supone que el daño foliar se inicia en el estoma donde se producen cambios estructurales hasta su destrucción, la modificación de las células adyacentes y la formación de lesiones superficiales en las hojas infectadas. En cuanto al agente, si bien no se pudo determinar en esta oportunidad, podría asociarse a algún tipo de virus. Se sugiere realizar futuros estudios para confirmar si los virus son los causantes de las lesiones. (AU)
Assuntos
Humanos , Epiderme Vegetal , Viscaceae , Infecções , Argentina , Plantas Medicinais , Erva-de-Passarinho , Fotomicrografia , Viscaceae , PhoradendronRESUMO
BACKGROUND: The aim of this study, is to investigate the in vitro antioxidant activity, the total phenols content, the flavonoids content and the antiproliferative activity of methanolic extracts of the plants: Krameria erecta, Struthanthus palmeri, Phoradendron californicum, Senna covesii and Stegnosperma halimifolium, used by different ethnic groups from northwestern Mexico in the treatment and cure of various diseases. METHODS: The in vitro antioxidant activity was measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and Ferric Reducing/Antioxidant Power assay (FRAP), the total phenols content was measured by Folin-Ciocalteau assay, the flavonoids content by the AlCl(3) colorimetric method and the antiproliferative activity (line cells HeLa, RAW 264.7, M12A(k).C3.F6 and L929) using MTT method. RESULTS: The K. erecta extract showed the higher radical scavenging activity (67.88%), antioxidant activity by FRAP (1.41 mg Trolox Eq), the highest total phenols content (598.51 mg Galic Acid Eq/g extract), the highest flavonoids content (3.80 mg Quercetin Eq/g extract) and the greatest antiproliferative activity in a dose dependent manner against most Cell line evaluated. A positive correlation was found between the antioxidant activity and the flavonoids content. CONCLUSIONS: This study is the first report on the antioxidant and antiproliferative activities of the five species evaluated. The results demostrate that there is a positive correlation between antioxidant activity and the flavonoids content, indicating that these type of polyphenols could be the major contributors to the observed antioxidant activity in the evaluated plant extracts. Of the extracts evaluated, that of Krameria erecta showed the greatest antioxidant and antiproliferative activities, a discovery that makes this species a promising candidate for future research.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Antioxidantes/uso terapêutico , Krameriaceae/química , Magnoliopsida/química , Neoplasias/terapia , Fitoterapia , Polifenóis/uso terapêutico , Animais , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Etnofarmacologia , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Células HeLa , Humanos , Loranthaceae/química , México , Camundongos , Fenóis/farmacologia , Fenóis/uso terapêutico , Phoradendron/química , Phytolaccaceae/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Polifenóis/farmacologia , Senna/químicaRESUMO
Phoradendron brachystachyum is a hemiparasitic plant widely distributed in México that belongs to the Viscaceae family. It has been commonly used in folk medicine as a substitute for the European mistletoe. In this chemical study, morolic acid was isolated as the major component (47.54% of the total composition of acetone extract) of this plant. In addition, 19 known compounds were identified: ß-sitosteryl and stigmasteryl linoleates, ß-sitosterol, stigmasterol, triacontanol, squalene, α- and ß-amyrin, lupeol, lupenone, betulin aldehyde, betulon aldehyde, oleanolic aldehyde, betulinic acid, betulonic acid, moronic acid, morolic acid, oleanolic acid, flavonoids acacetin and acacetin 7-methyl ether. There have been no previous reports in the literature on the chemical composition of this potential natural source of hypoglycaemic and antihypertensive compounds.
Assuntos
Phoradendron/química , Componentes Aéreos da Planta/química , Extratos Vegetais/análise , Triterpenos/análise , Acetona , Aldeídos/análise , Aldeídos/isolamento & purificação , Cromatografia em Camada Fina , Álcoois Graxos/análise , Álcoois Graxos/isolamento & purificação , Flavonoides/análise , Flavonoides/isolamento & purificação , Ácidos Linoleicos/análise , Ácidos Linoleicos/isolamento & purificação , Espectroscopia de Ressonância Magnética , México , Estrutura Molecular , Fitosteróis/análise , Fitosteróis/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Espectrofotometria Infravermelho , Triterpenos/isolamento & purificaçãoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Phoradendron serotinum is commonly used in Mexican traditional medicine for the empirical treatment of cancer. However, there are no studies regarding the antitumoral or immunomodulatory activities of Phoradendron serotinum. MATERIALS AND METHODS: The in vivo toxicity of ethanolic extracts of Phoradendron serotinum (PSE) was evaluated in mice according to the Lorke procedure. The in vitro immunomodulatory effects of PSE were evaluated estimating the effects of PSE on the pinocytosis, NO production and lysosomal enzyme activity in murine macrophages RAW 264.7. The effects of PSE on the proliferation of murine splenocytes and NK cell activity were also assayed. The cytotoxic effects on TC-1 (lung murine cancer cells) were evaluated using the MTT assay, whereas the apoptotic effect of PSE on TC-1 cells was evaluated using TUNEL assay. Also, different doses of PSE were injected intraperitoneally daily into C57BL/6 mice bearing tumors of TC-1 cells during 25 days. The growth and weight of tumors was measured. In addition, the levels of IL-2, IL-6, IL-12, IL-23 and IFN-γ in murine serum and supernatants of K562 cell-murine splenocyte cocultures were measured. RESULTS: PSE stimulated the proliferation, pinocytosis and lysosomal enzyme activity in murine macrophages with a similar potency than lypopolisaccharides 1 µg/ml. In addition, PSE stimulated the proliferation of murine splenocytes and induced the NK cell activity. PSE showed cytotoxic (IC(50)=1.9 µg/ml) and apoptotic effects against TC-1 cells. The LD(50) was 125 mg/kg by intraperitoneal route (i.p.) and 375 mg/kg by oral route. PSE administrated at 1, 5 and 10 mg/kg i.p. inhibited the tumor growth by 18%, 40% and 69%, respectively, in mice bearing TC-1 tumor. PSE increased the in vitro and in vivo release of IL-2, IL-6 and IFN-γ but lacked effect on IL-12 and IL-23 release. CONCLUSIONS: Phoradendron serotinum shows moderate toxic effects in vivo, exerts cytotoxic and apoptotic effects on TC-1 cells. Phoradendron serotinum also has antitumor effects in mice bearing TC-1 tumor and induces immunomodulatory activities in vivo. The results suggest that antitumoral effects of PSE are related with the production of immunity-related cytokines.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Neoplasias/tratamento farmacológico , Phoradendron , Extratos Vegetais/uso terapêutico , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citocinas/imunologia , Humanos , Fatores Imunológicos/farmacologia , Células K562 , Células Matadoras Naturais/efeitos dos fármacos , Dose Letal Mediana , Lisossomos/metabolismo , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias/metabolismo , Neoplasias/patologia , Óxido Nítrico/metabolismo , Extratos Vegetais/farmacologia , Folhas de Planta , Carga Tumoral/efeitos dos fármacosRESUMO
The aim of the current study was to investigate the vasorelaxant activity of five structurally-related triterpenic acids namely ursolic (1), moronic (2), morolic (3), betulinic (4) and 3,4-seco-olean-18-ene-3,28-dioic (5) acids. The vasorelaxant effect of compounds 1-5 were determined on endothelium-denuded and endothelium-intact rat aortic rings pre-contracted with noradrenaline (0.1 µM). All compounds showed significant relaxant effect on endothelium-intact vessels in a concentration-dependent manner (p<0.05). Ursolic, moronic and betulinic acids were the most potent vasorelaxant agents with 11.7, 16.11 and 58.46 µM, respectively. Since vasorelaxation was blocked by L-NAME, while indomethacin did not inhibit the effect, endothelium-derived nitric oxide seems to be involved in triterpenic 2 and 3 mode of action. Compounds 1-5 were docked with a crystal structure of eNOS. Triterpenes 1-5 showed calculated affinity with eNOS in the C1 and C2 binding pockets, near the catalytic site; Ser248 and Asp480 are the residues that make hydrogen bonds with the triterpene compounds.
Assuntos
Endotélio Vascular/efeitos dos fármacos , Óxido Nítrico/biossíntese , Phoradendron/química , Extratos Vegetais/farmacologia , Triterpenos/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Aorta , Relação Dose-Resposta a Droga , Ligação de Hidrogênio , Indometacina/farmacologia , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase Tipo III/metabolismo , Extratos Vegetais/química , Ratos , Triterpenos/isolamento & purificação , Vasodilatadores/isolamento & purificaçãoRESUMO
Foram investigados os efeitos miorelaxante, antiespasmódico e antinociceptivo do extrato aquoso liofilizado das folhas da Phoradendron piperoides. A toxicidade aguda também foi avaliada. No íleo isolado de cobaio, o extrato aquoso da P. piperoides (0,05 - 2,0 mg/mL) produziu relaxamento de forma concentração-dependente (IC50 = 0,114 mg/mL) e, na concentração de 1,5 mg/mL, reduziu a amplitude das contrações induzidas por carbacol (2 μM), histamina (2 μM) e BaCl2 (0,03 M) em 46,6; 38,6 e 55,3 por cento (p < 0,001), respectivamente. Em camundongos, o extrato aquoso liofilizado (100-400 mg/kg) não reduziu de forma significativa as contorções abdominais induzidas por ácido acético, não modificou o tempo de reação dos animais no teste da formalina e não aumentou o tempo de latência ao calor no teste da placa quente. No ensaio de toxicidade aguda utilizado, não foi detectada a morte de nenhum animal após tratamento com doses de até 5 g/kg (p.o.) do extrato. Em conclusão, os resultados obtidos indicam que o extrato aquoso da P. piperoides apresenta efeito antiespasmódico e baixa toxicidade aguda. O extrato, no entanto, não possui efeito antinociceptivo.
The present work evaluated the antinociceptive, miorelaxant and antispasmodic effects as well as the acute toxicity of the aqueous extract from leaves of Phoradendron piperoides. In guinea pig ileum, the plant extract (0.05 - 2.0 mg/kg) decreased the preparations basal tone in a dose-dependent manner (IC50 = 0.114 mg/mL) and it (1.5 mg/mL) reduced (p < 0.001) the contractions induced by carbachol (2 μM), histamine (2 μM) and BaCl2 (0.03M). The extract, at oral doses of 100, 200, and 400 mg/kg, did not manifest a significant antinociceptive effect in the writhing, formalin and hot-plate tests. Moreover, no animal deaths were observed in doses up to 5 g/kg. In conclusion, the aqueous extract of Phoradendron piperoides showed no antinociceptive effect and no acute toxicity in mice. Indeed, it revealed miorelaxant and antispasmodic activities that are probably miogenic and not specific for neurotransmitters.
Assuntos
Animais , Ratos , Analgésicos , Parassimpatolíticos , Phoradendron , Toxicidade , ViscaceaeAssuntos
Férias e Feriados , Plantas/intoxicação , Segurança , Idoso , Criança , Euphorbia/intoxicação , Humanos , Phoradendron/intoxicaçãoRESUMO
Phoradendron liga (Gill. ex H. et A.) Eichl. is a Viscaceae widely distributed in Argentina. It has been commonly used in folk medicine as a substitute of the European mistletoe (Viscum album L.) to decrease high blood pressure due to their external similarity. In this study, the anatomical features as well as micromolecular and macromolecular analysis of this species are reported. Anatomical study has shown that Phoradendron liga presents as anatomic features: papillous cuticle, clusters in leaves and stems, and isodiametric stone cells only in stems. The analysis of flavonoids showed that this species produces C-glycosylflavones and 3-desoxyproanthocyanidins. Protein study showed a protein pattern with components ranging from 14 to 90 kDa and the presence of related epitopes between the species was demonstrated by cross recognition using anti-Phoradendron and anti-Viscum antisera of both species by Western blot assay. In addition, a galactose specific lectin (L-Phl) was isolated form Phoradendron liga extracts. These results are part of a comprehensive project on Argentine hemiparasite species destinated to be applied to quality control of commercial samples and disclosed their potential use as a potential source for immunomodulatory compounds.