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1.
J Biochem Mol Toxicol ; 35(10): e22868, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34338395

RESUMO

Osteosarcoma (OS) is a primary bone neoplasm that is highly malignant. As advances in chemotherapy for the treatment of OS have stagnated, discovery of new reagents is required. Emetine is a phytochemical which can be isolated from a medicinal herb Cephaelis ipecacuanha and is traditionally used for amoebicides. Previous studies have demonstrated that emetine can possibly be repositioned for use in anticancer reagents. However, any anticancer effects and underlying mechanisms of emetine on human OS are not yet well understood. In this study, we analyzed the anticancer effects and involved cellular mechanisms after treatment with emetine to U2OS human OS cells. Emetine significantly reduced both the viability and proliferation, and induced apoptosis via activation of caspase-3 and caspase-7 in U2OS cells. Emetine effectively inhibited the migration and invasion of U2OS cells. Gelatinase activities of matrix metalloproteinase 2 (MMP-2) and MMP-9 were reduced by emetine. MMP-9 was transcriptionally inhibited, while MMP-2 was posttranscriptionally repressed, via the reduced expression of membrane-type I-matrix metalloproteinase (MT1-MMP). p38, which is closely related with induction of apoptosis, was stimulated by emetine. Extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and ß-catenin, which are linked with expression of MMPs, were downregulated. Emetine exerted anticancer effects on MG63 human OS cells as well. Taken together, our study demonstrated the anticancer and antimetastatic potential of emetine in treating human OS for the first time. It is expected that emetine may be a promising drug candidate to be repositioned for chemotherapy of OS.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Ósseas/metabolismo , Cephaelis/química , Emetina/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Osteossarcoma/metabolismo , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , beta Catenina/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Apoptose/efeitos dos fármacos , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Osteossarcoma/patologia
2.
J Nat Prod ; 84(8): 2238-2248, 2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34308635

RESUMO

Cyclotides are plant-derived disulfide-rich peptides comprising a cyclic cystine knot, which confers remarkable stability against thermal, proteolytic, and chemical degradation. They represent an emerging class of G protein-coupled receptor (GPCR) ligands. In this study, utilizing a screening approach of plant extracts and pharmacological analysis we identified cyclotides from Carapichea ipecacuanha to be ligands of the κ-opioid receptor (KOR), an attractive target for developing analgesics with reduced side effects and therapeutics for multiple sclerosis (MS). This prompted us to verify whether [T20K]kalata B1, a cyclotide in clinical development for the treatment of MS, is able to modulate KOR signaling. T20K bound to and fully activated KOR in the low µM range. We then explored the ability of T20K to allosterically modulate KOR. Co-incubation of T20K with KOR ligands resulted in positive allosteric modulation in functional cAMP assays by altering either the efficacy of dynorphin A1-13 or the potency and efficacy of U50,488 (a selective KOR agonist), respectively. In addition, T20K increased the basal response upon cotreatment with U50,488. In the bioluminescence resonance energy transfer assay T20K negatively modulated the efficacy of U50,488. This study identifies cyclotides capable of modulating KOR and highlights the potential of plant-derived peptides as an opportunity to develop cyclotide-based KOR modulators.


Assuntos
Ciclotídeos/farmacologia , Receptores Opioides kappa/agonistas , Transdução de Sinais/efeitos dos fármacos , Cephaelis/química , Células HEK293 , Humanos , Ligantes , Extratos Vegetais/química
3.
J Vis Exp ; (133)2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29608154

RESUMO

Adventitious shoot formation is an important technique for the propagation of economically important crops and for the regeneration of transgenic plants. Phytohormone treatment is required for the induction of adventitious shoots in most species. Whether adventitious shoots can be induced is determined by the balance between auxin and cytokinin (CK) levels. Much effort goes into determining optimum concentrations and combinations of phytohormones in each tissue used as explants and in each plant species. In ipecac, however, adventitious shoots can be induced on internodal segments in culture medium without phytohormone treatment. This allows the inherent plasticity of ipecac for cell differentiation to be evaluated. To induce adventitious shoots in ipecac, we cultured internodal segments at 24 °C under 15 µmol m-2 s-1 of light in a 14-h light/10-h dark cycle on phytohormone-free B5 medium solidified with 0.2% gellan gum for 5 weeks. To investigate phytohormone dynamics during adventitious shoot formation, we measured endogenous indole-3-acetic acid and CKs in the segments by liquid chromatography-tandem mass spectrometry LC-MS/MS. This method allows analysis of endogenous indole-3-acetic acid and CKs levels in a simple manner. It can be applied to investigate the dynamics of endogenous auxin and CK during organogenesis in other plant species.


Assuntos
Cephaelis/metabolismo , Cromatografia Líquida/métodos , Citocininas/metabolismo , Ácidos Indolacéticos/metabolismo , Espectrometria de Massas em Tandem/métodos , Cephaelis/química , Citocininas/análise , Ácidos Indolacéticos/análise , Brotos de Planta/química , Brotos de Planta/metabolismo
4.
Yakugaku Zasshi ; 137(12): 1443-1482, 2017.
Artigo em Japonês | MEDLINE | ID: mdl-29199255

RESUMO

Studies on the structural determination, biosynthesis, and biological activities of secondary metabolites from natural sources are significant in the field of natural products chemistry. This review focuses on diverse secondary metabolites isolated from medicinal plants and cultivated mycobionts of lichens in our laboratory. Monoterpene-tetrahydroisoquinoline glycosides and alkaloids isolated from Cephaelis acuminata and Alangium lamarckii gave important information on the biosynthesis of ipecac alkaloids. A variety of glycosides linked with a secologanin unit and indole alkaloids were obtained from medicinal plants belonging to the families of Rubiaceae, Apocynaceae, and Loganiaceae. Plant species of the four genera Fraxinus, Syringa, Jasminum, and Ligustrum of the family Oleaceae were chemically investigated to provide several types of secoiridoid and iridoid glucosides. The biosynthetic pathway leading from protopine to benzophenanthridine alkaloids in suspension cell cultures of Eschscholtzia californica was elucidated. The structures and biological activities of the bisbenzylisoquinoline alkaloids of Stephania cepharantha and Nelumbo nucifera were also investigated. In addition, the mycobionts of lichens were cultivated to afford various types of metabolites that differ from the lichen substances of intact lichens but are structurally similar to fungal metabolites. The biosynthetic origins of some metabolites were also studied. These findings suggest that cultures of lichen mycobionts could be sources of new bioactive compounds and good systems for investigating secondary metabolism in lichens.


Assuntos
Alcaloides/isolamento & purificação , Glicosídeos/isolamento & purificação , Líquens/metabolismo , Plantas Medicinais/metabolismo , Alangiaceae/metabolismo , Alcaloides/biossíntese , Alcaloides/química , Benzilisoquinolinas , Cephaelis/metabolismo , Eschscholzia/metabolismo , Glicosídeos/biossíntese , Glicosídeos/química , Iridoides , Monoterpenos , Oleaceae/metabolismo , Rubiaceae/metabolismo , Stephania/metabolismo , Tetra-Hidroisoquinolinas
5.
Planta Med ; 82(11-12): 1009-15, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27145237

RESUMO

Human ether-a-go-go-related gene channel blocking is associated with QT interval prolongation and increased risk of potentially fatal arrhythmias. As natural products keep increasing in popularity, there is an urgent need for studies assessing human ether-a-go-go-related gene channel-related cardiotoxic risks. We selected 49 plant species based on the results of a pharmacophore-based virtual screening campaign, in parallel with a literature data survey concerning highly consumed herbal medicines with reported cardiac liabilities. Lead-like enhanced extracts were prepared, an initial in vitro screening was performed at 100 µg/mL by voltage clamp on Xenopus oocytes, and five human ether-a-go-go-related gene channel blocking extracts were identified. In accordance to the six virtually predicted alkaloids, the root extract of Carapichea ipecacuanha inhibited human ether-a-go-go-related gene channel currents by 32.5 %. A phytochemical workflow resulted in the isolation and identification of five out of the six virtually predicted alkaloids. All isolates blocked human ether-a-go-go-related gene channel currents to different extents. The major ipecac constituents emetine (1) and cephaeline (2) showed IC50 values of 21.4 and 5.3 µM, respectively, measured by whole-cell patch clamp in HEK293 cells. This is the first report on human ether-a-go-go-related gene channel blockers from C. ipecacuanha. Its roots and rhizomes are used to produce different pharmacopeial ipecac preparations that are mainly used as emetics for poisoning treatment. Our findings raise further questions regarding the safety and over-the-counter appropriateness of these herbal products.


Assuntos
Alcaloides/farmacologia , Cephaelis/química , Canais de Potássio Éter-A-Go-Go/antagonistas & inibidores , Ipeca/farmacologia , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Simulação por Computador , Humanos , Ipeca/química , Estrutura Molecular , Xenopus laevis
6.
Rev. colomb. biotecnol ; 16(1): 86-92, ene.-jun. 2014. ilus
Artigo em Espanhol | LILACS | ID: lil-715301

RESUMO

Psychotria ipecacuanha (Brot.) Stokes (Rubiaceae Juss), es una especie vegetal con reconocidas propiedades medicinales. Esta especie se encuentra en peligro crítico de extinción, debido a la sobreexplotación de las poblaciones naturales. Conociendo además las dificultades para su propagación por medio de semillas (debido a la baja tasa de germinación y elevada muerte prematura de las plántulas) y por vía vegetativa (lento crecimiento), el presente trabajo tuvo como objetivo evaluar el potencial de propagación vía embriogénesis somática directa. Segmentos de hojas jóvenes de plantas mantenidas en casa malla fueron desinfectados y sembrados en el medio de cultivo MS (Murashige y Skoog) suplementado con diferentes concentraciones y combinaciones de reguladores de crecimiento. Las combinaciones IBA y BAP a 1 y 2 mg/L y 2 y 1 mg/L, respectivamente; mostraron ser efectivas en la formación de embriones somáticos en esta especie. La procedencia de la planta donadora parece tener influencia en la sensibilidad del tejido foliar a la respuesta. Este es el primer reporte de embriogénesis somática directa para esta especie y el primer reporte de cultivo in vitro de poblaciones colombianas.


Psychotria ipecacuanha (Brot.) Stokes (Rubiaceae Juss), is a specie with known medicinal properties. This species is critically endangered due to overexploitation of natural populations.Besides knowing the difficulties in propagation by seed (due to the low rate of germination and high seedling premature death) and by vegetative (slow growth), the present study evaluated the potential for propagation by using direct somatic embryogenesis.Young leaves segments from plants cultivated in a greenhouse were disinfected and planted in MS medium (Murashige y Skoog), supplemented with different concentrations of growth regulators. IBA and BAP combinations at 1 and 2 mg / L and 2 and 1 mg / L, respectively, shown to be effective in the formation of somatic embryos in this species. The origin of the donor plant seems to influence foliar tissue sensitivity to the answer. This is the first report of direct somatic embryogenesis for this species and the first report of in vitro culture of Colombian populations.


Assuntos
Espécies em Perigo de Extinção , Ipecacuanha , Plantas Medicinais , Política Ambiental , Regeneração
7.
Int. j. high dilution res ; 13(48): 182-186, 2014.
Artigo em Inglês | HomeoIndex - Homeopatia, HomeoIndex - Homeopatia | ID: hom-11042

RESUMO

A major catastrophe hit Western Africa and we would like to put a definite end to that nightmare. Ever since in its initial identification in 1976, the Ebola virus is endemic in Zaire (currently, Democratic Republic of the Congo – DRC), where it has exerted devastating effects. For many years now, the virus has mercilessly attacked our fellow men, killing entire families overnight and leaving thousands of children orphan.The current, being the seventh epidemic of Ebola hemorrhagic fever (EHF) in the RDC, also broke out in West Africa - Guinea, Liberia, Sierra Leone Nigeria and Senegal.The World Health Organization (WHO) called specialists from several countries and concentrated efforts that might result in a practical contribution to the control of cases. It is worth to observe that the epidemic has caused more than 1,400 deaths in 2014, being the fatality rate 60 to 90%.(AU)


Assuntos
Humanos , Doença pelo Vírus Ebola/terapia , Fósforo/uso terapêutico , Crotalus horridus/uso terapêutico , Ipecacuanha/uso terapêutico , Terapêutica Homeopática , Dengue/epidemiologia , Gênio Epidêmico/prevenção & controle
8.
Int. j. high dilution res ; 13(48): 182-186, 2014.
Artigo em Inglês | LILACS | ID: lil-754745

RESUMO

A major catastrophe hit Western Africa and we would like to put a definite end to that nightmare. Ever since in its initial identification in 1976, the Ebola virus is endemic in Zaire (currently, Democratic Republic of the Congo – DRC), where it has exerted devastating effects. For many years now, the virus has mercilessly attacked our fellow men, killing entire families overnight and leaving thousands of children orphan.The current, being the seventh epidemic of Ebola hemorrhagic fever (EHF) in the RDC, also broke out in West Africa - Guinea, Liberia, Sierra Leone Nigeria and Senegal.The World Health Organization (WHO) called specialists from several countries and concentrated efforts that might result in a practical contribution to the control of cases. It is worth to observe that the epidemic has caused more than 1,400 deaths in 2014, being the fatality rate 60 to 90%.


Assuntos
Humanos , Crotalus horridus/uso terapêutico , Doença pelo Vírus Ebola/terapia , Ipecacuanha/uso terapêutico , Fósforo/uso terapêutico , Terapêutica Homeopática , Dengue/epidemiologia , Gênio Epidêmico/prevenção & controle
9.
J Ethnopharmacol ; 142(3): 762-8, 2012 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-22683904

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Like many traditional medical systems found at Latin America, the very existence of a Brazilian traditional medical system is debated. Despite the absence of written material and organized knowledge, there is little doubt that Brazilians from all regions and all social classes recognize and access an estimated 4000 plant species with alleged therapeutic purposes as well as medicinal practices ranging from bone setting to spiritual healing. This "Brazilian folk medicine" is usually described as a rich mixture of African, European, and Indigenous medical traditions. AIM OF THE STUDY: This study questions this view, and argues it is both simplistic and Eurocentric. MATERIALS AND METHODS: By scrutinizing the origins of the medical uses of Zingiberis officinale, Curcuma longa, Ruta officinalis, Cephaelis ipecacuanha, Pilocarpus pinnatifolius, and curare (Chondrodendron, Abuta and Curarea), we illustrate the intense circulation of materials during imperial times. We further discuss how these practices articulated with local medical knowledge, and exemplify some of the ways by which knowledge was produced, transformed, incorporated, and resignified over time. DISCUSSION: Though not a systematic or comprehensive analysis of Brazilian folk medicine development, these selected examples show that, in opposition to usual simplistic descriptions, complex and convoluted manners of medicinal plant development occurred over time to compound both the Brazilian and European pharmaceutical armamentarium.


Assuntos
Disseminação de Informação , Medicina Tradicional , Plantas Medicinais , Brasil , Cephaelis , Curare , Curcuma , Etnofarmacologia , Gengibre , Humanos , Pilocarpus , Portugal , Ruta
10.
Homeopatia Méx ; 81(678): 4-18, mayo-jun. 2012.
Artigo em Espanhol | HomeoIndex - Homeopatia, HomeoIndex - Homeopatia | ID: hom-10754

RESUMO

El tratamiento del asma con Homeopatía exige el conocimiento y la destreza del médico para elegir medicamentos adecuados en dos momentos distintos: durante las crisis, en las que se debe actuar con prontitud para permitir la adecuada respiración del paciente, y para corregir la constitución de fondo del caso, a fin de regular la alteración de la respuesta inmunológica y evitar que las fases agudas vuelvan a presentarse.(AU)


Asthma management with homeopathy requires the knowledge and skill of the physician to select appropriate drugs at two different moments: during the crisis, in which the physician must act quickly to allow adequate breathing of the patient, and in a second time to correct the constitution of the patient, in order to regulate the alteration of the immune response and prevent that acute phases will appear again.(AU)


Assuntos
Humanos , Asma , Antimonium Tartaricum , Arsenicum Album , Ipecacuanha , Kali Carbonicum , Sambucus nigra , Ignatia amara , Lycopodium clavatum , Pulsatilla nigricans , China officinalis
11.
Homeopatia Méx ; 81(678): 4-18, mayo-jun. 2012.
Artigo em Espanhol | LILACS | ID: lil-654550

RESUMO

El tratamiento del asma con Homeopatía exige el conocimiento y la destreza del médico para elegir medicamentos adecuados en dos momentos distintos: durante las crisis, en las que se debe actuar con prontitud para permitir la adecuada respiración del paciente, y para corregir la constitución de fondo del caso, a fin de regular la alteración de la respuesta inmunológica y evitar que las fases agudas vuelvan a presentarse.


Asthma management with homeopathy requires the knowledge and skill of the physician to select appropriate drugs at two different moments: during the crisis, in which the physician must act quickly to allow adequate breathing of the patient, and in a second time to correct the constitution of the patient, in order to regulate the alteration of the immune response and prevent that acute phases will appear again.


Assuntos
Humanos , Antimonium Tartaricum , Arsenicum Album , Asma , China officinalis , Ignatia amara , Ipecacuanha , Kali Carbonicum , Lycopodium clavatum , Pulsatilla nigricans , Sambucus nigra
12.
Rev. bras. plantas med ; 14(2): 335-343, 2012. ilus, tab
Artigo em Português | LILACS | ID: lil-650675

RESUMO

O Brasil está entre os principais exportadores de poaia [Psychotria ipecacuanha (Brot.) Stoves] seguido do Panamá e Costa Rica. A poaia brasileira apresenta alto valor farmacológico das raízes devido aos teores de emetina e cefalina. Este trabalho teve como objetivo descrever como as famílias de poaieiros mantém a memória cultural sobre a Psychotria ipecacuanha (Brot.) Stoves. As informações foram coletadas no município de Cáceres, Mato Grosso, através de entrevista estruturada e observação participante com 20 homens e 10 mulheres, de faixa etária de 45 a 86 anos. Foram citadas as formas de utilização na alimentação para animais, inseticida, carrapaticida, emético, contra diarréias, para alívio de dor de cabeça, contra malária, bronquite e dor no estômago. A raiz é a parte mais usada e a forma de preparo é tintura ou misturada ao fumo, ao vinho ou à cachaça. Poucos entrevistados passaram aos filhos o conhecimento sobre a P. ipecacuanha. A memória cultural sobre a P. ipecacuanha deve-se a vivência, extração e comercialização da planta, e por ouvir as conversas dos pais com amigos. A perda de conhecimento associado a poaia é causada pelo êxodo rural, destruição do habitat com o desmatamento e ocupação agrícola. A extinção da espécie na região contribui para a erosão cultural.


Brazil is among the leading exporters of ipecac [Psychotria ipecacuanha (Brot.) Stoves], followed by Panama and Costa Rica. The roots of Brazilian ipecac have high pharmacological value due to their levels of emetine and cephalin. This study aimed to describe how families of "poaieiros" maintain the cultural memory of Psychotria ipecacuanha (Brot.) Stoves. Information was collected in the city of Cáceres, Mato Grosso State, Brazil, through structured interviews and participating observation involving 20 men and 10 women aged from 45 to 86 years. The cited forms of use were in animal nutrition, as insecticide, acaricide, emetic, against diarrhea, relief from headache, and against malaria, bronchitis and stomach ache. The root is the most used part and its preparation form is tincture or mixed with tobacco, wine or sugarcane. Few interviewees transmitted to their children the knowledge of P. ipecacuanha. The cultural memory of P. ipecacuanha is due to experience, extraction and marketing of the plant, as well as to hearing conversations between parents and friends. The loss of knowledge associated with ipecac is caused by rural exodus, destruction of its habitat due to deforestation and agricultural occupation. The extinction of this species in the region contributes to cultural erosion.


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Antropologia Cultural/instrumentação , Ipecacuanha/história , Ipeca/classificação , Etnobotânica/métodos , Pradaria
13.
J Ethnopharmacol ; 138(3): 756-61, 2011 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-22041104

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Several roots or rhizomes of rubiaceous species are reportedly used as the emetic and antiamoebic drug ipecac. True ipecac (Carapichea ipecacuanha) is chemically well characterized, in contrast to striated or false ipecac derived from the rhizomes of Ronabea emetica (syn. Psychotria emetica). Besides its previous use as substitute of ipecac, the latter species is applied in traditional medicine of Panama and fruits of its relative Ronabea latifolia are reported as curare additives from Colombia. MATERIALS AND METHODS: Compounds of Ronabea emetica were isolated using standard chromatographic techniques, and structurally characterized by NMR spectroscopy and mass spectrometry. Organ specific distribution in Ronabea emetica as well as in Ronabea latifolia was further assessed by comparative HPLC analysis. RESULTS: Four iridoid-glucosides, asperuloside (1), 6α-hydroxygeniposide (2), deacetylasperulosidic acid (3) and asperulosidic acid (4) were extracted from leaves of Ronabea emetica. Rhizomes, used in traditional medicine, were dominated by 3. HPLC profiles of Ronabea latifolia were largely corresponding. These results contrast to the general tendency of producing emetine-type and indole alkaloids in species of Psychotria and closely related genera and merit chemotaxonomic significance, characterizing the newly delimited genus Ronabea. CONCLUSIONS: The aim of the work was to resolve the historic problem of adulteration of ipecac by establishing the chemical profile of Ronabea emetica, the false ipecac, as one of its less known sources. The paper demonstrates that different sources of ipecac can be distinguished by their phytochemistry, thus contributing to identifying adulterations of true ipecac.


Assuntos
Antieméticos/análise , Cephaelis/química , Iridoides/análise , Extratos Vegetais/análise , Psychotria/química , Cromatografia Líquida de Alta Pressão , Contaminação de Medicamentos , Frutas/química , Espectroscopia de Ressonância Magnética , Folhas de Planta/química , Caules de Planta/química , Plantas Medicinais/química , Rizoma/química
14.
J Biol Chem ; 285(10): 7722-38, 2010 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-20061395

RESUMO

The medicinal plant Psychotria ipecacuanha produces ipecac alkaloids, a series of monoterpenoid-isoquinoline alkaloids such as emetine and cephaeline, whose biosynthesis derives from condensation of dopamine and secologanin. Here, we identified three cDNAs, IpeOMT1-IpeOMT3, encoding ipecac alkaloid O-methyltransferases (OMTs) from P. ipecacuanha. They were coordinately transcribed with the recently identified ipecac alkaloid beta-glucosidase Ipeglu1. Their amino acid sequences were closely related to each other and rather to the flavonoid OMTs than to the OMTs involved in benzylisoquinoline alkaloid biosynthesis. Characterization of the recombinant IpeOMT enzymes with integration of the enzymatic properties of the IpeGlu1 revealed that emetine biosynthesis branches off from N-deacetylisoipecoside through its 6-O-methylation by IpeOMT1, with a minor contribution by IpeOMT2, followed by deglucosylation by IpeGlu1. The 7-hydroxy group of the isoquinoline skeleton of the aglycon is methylated by IpeOMT3 prior to the formation of protoemetine that is condensed with a second dopamine molecule, followed by sequential O-methylations by IpeOMT2 and IpeOMT1 to form cephaeline and emetine, respectively. In addition to this central pathway of ipecac alkaloid biosynthesis, formation of all methyl derivatives of ipecac alkaloids in P. ipecacuanha could be explained by the enzymatic activities of IpeOMT1-IpeOMT3, indicating that they are sufficient for all O-methylation reactions of ipecac alkaloid biosynthesis.


Assuntos
Cephaelis , Eméticos/metabolismo , Emetina/análogos & derivados , Emetina/biossíntese , Isoenzimas/metabolismo , Metiltransferases/metabolismo , Cephaelis/anatomia & histologia , Cephaelis/química , Cephaelis/enzimologia , Cromatografia Líquida , Eméticos/química , Emetina/química , Isoenzimas/classificação , Isoenzimas/genética , Metilação , Metiltransferases/classificação , Metiltransferases/genética , Dados de Sequência Molecular , Estrutura Molecular , Filogenia , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Espectrometria de Massas em Tandem
15.
Genetica ; 136(1): 57-67, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-18679809

RESUMO

Ipecac (Psychotria ipecacuanha) is a perennial, medicinal herb that grows in the understory of semi-deciduous tropical forests in the Neotropics. Ipecacs present a widely disjunct distribution, with two of its three ranges occurring in Brazil. The Amazonian populations are at least 1600 km from the nearest Atlantic populations. This work used ISSR markers to compare the genetic diversity and structure of populations from the two Brazilian ranges. Lower genetic diversity in Amazon populations (P = 60.11%, Hs = 0.18) and higher genetic diversity in Atlantic populations (P = 73.94%, Hs = 0.20) were detected. Differentiation between ranges were high (theta (B) = 0.6838, G(ST)-B = 0.6665). AMOVA revealed that 65.3% of the total molecular variance can be attributed to regional differences between the two ranges. Principal coordinate analyses and cluster analyses organized ipecacs at either individual or population level into two exclusive groups that correspond each to one of the two disjunct ranges, without exception. The results do not support a scenario that postulates human-mediated, long-distance dispersal events as a plausible origin for the distribution of the Brazilian ipecacs, but indicate geographic isolation as a long-standing barrier to genetic exchange and connectivity among populations from different ranges. Conservation implications are discussed.


Assuntos
Cephaelis/genética , Variação Genética , Conservação dos Recursos Naturais , DNA de Plantas/química , Evolução Molecular , Genética Populacional , Geografia , Filogenia
16.
J Biol Chem ; 283(50): 34650-9, 2008 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-18927081

RESUMO

Ipecac alkaloids produced in the medicinal plant Psychotria ipecacuanha such as emetine and cephaeline possess a monoterpenoid-tetrahydroisoquinoline skeleton, which is formed by condensation of dopamine and secologanin. Deglucosylation of one of the condensed products N-deacetylisoipecoside (1 alpha(S)-epimer) is considered to be a part of the reactions for emetine biosynthesis, whereas its 1 beta(R)-epimer N-deacetylipecoside is converted to ipecoside in P. ipecacuanha. Here, we isolated a cDNA clone Ipeglu1 encoding Ipecac alkaloid beta-D-glucosidase from P. ipecacuanha. The deduced protein showed 54 and 48% identities to raucaffricine beta-glucosidase and strictosidine beta-glucosidase, respectively. Recombinant IpeGlu1 enzyme preferentially hydrolyzed glucosidic Ipecac alkaloids except for their lactams, but showed poor or no activity toward other substrates, including terpenoid-indole alkaloid glucosides. Liquid chromatography-tandem mass spectrometry analysis of deglucosylated products of N-deacetylisoipecoside revealed spontaneous transitions of the highly reactive aglycons, one of which was supposed to be the intermediate for emetine biosynthesis. IpeGlu1 activity was extremely poor toward 7-O-methyl and 6,7-O,O-dimethyl derivatives. However, 6-O-methyl derivatives were hydrolyzed as efficiently as non-methylated substrates, suggesting the possibility of 6-O-methylation prior to deglucosylation by IpeGlu1. In contrast to the strictosidine beta-glucosidase that stereospecifically hydrolyzes 3 alpha(S)-epimer in terpenoid-indole alkaloid biosynthesis, IpeGlu1 lacked stereospecificity for its substrates where 1 beta(R)-epimers were preferred to 1 alpha(S)-epimers, although ipecoside (1 beta(R)) is a major alkaloidal glucoside in P. ipecacuanha, suggesting the compartmentalization of IpeGlu1 from ipecoside. These facts have significant implications for distinct physiological roles of 1 alpha(S)- and 1 beta(R)-epimers and for the involvement of IpeGlu1 in the metabolic fate of both of them.


Assuntos
Alcaloides/química , Cephaelis/enzimologia , Isoquinolinas/química , Terpenos/química , beta-Glucosidase/química , Bioquímica/métodos , Cephaelis/metabolismo , DNA Complementar/metabolismo , Escherichia coli/metabolismo , Cinética , Modelos Químicos , Dados de Sequência Molecular , Filogenia , Estrutura Terciária de Proteína , Proteínas Recombinantes/química , Especificidade por Substrato
17.
Kardern; Narayana; 2008. 96 p.
Monografia em Inglês | HomeoIndex - Homeopatia, HomeoIndex - Homeopatia | ID: biblio-1337787
18.
Planta Med ; 73(13): 1389-96, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17912675

RESUMO

Cytotoxic and apoptosis-inducing effects of the alkaloid emetine from Psychotria ipecacuanha (Rubiaceae) were studied in human cell lines. In Jurkat T-cells emetine leads to phosphatidylserine exposure, mitochondrial depolarisation, and DNA fragmentation. Furthermore, activation of several caspases (caspase-3, -9/6, and -8) was demonstrated in a fluorescent caspase assay. Bcl-2 over-expressing cells are less sensitive to emetine while caspase-8-deficient Jurkat T-cells react similarly to wild-type cells. This indicates that apoptosis induction is mediated via the mitochondrial pathway. By using hepatoma cell lines with differing p53 expression, it was concluded that p53 does not seem to play a role in apoptosis induction by emetine. Alterations of protein profiles during emetine-induced apoptosis were analysed by 2D-PAGE and MALDI-TOF-MS. A new protein spot was apparent after treatment with emetine: It could be identified as the N-terminal fragment lamin B1, which is released after cleavage by caspase-6.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Cephaelis , Emetina/farmacologia , Fitoterapia , Alcaloides/administração & dosagem , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/uso terapêutico , Relação Dose-Resposta a Droga , Emetina/administração & dosagem , Emetina/uso terapêutico , Citometria de Fluxo , Humanos , Células Jurkat/efeitos dos fármacos
19.
Braz J Biol ; 66(1A): 151-9, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16680318

RESUMO

Reproductive studies were carried out on Brazilian accessions of ipecac, Cephaelis ipecacuanha. Meiotic behavior was studied using the squashing technique. Irregular chromosome segregation in meiosis I and II, many sets of chromosomes in telophase II, micronuclei, incorrect cytoplasm division, incomplete cytokinesis and anomalous post-meiotic products, mainly polyads, were observed. The mean meiotic index was lower than 72%. Pollen viability was analyzed using Alexander solution, and the percentages ranged between brevistylous and longistylous floral morphs (85.3 to 93.1%), and among different localities (82.5 to 92.6%) analyzed. The size of pollen ranged between viable and sterile, and empty and shrunken sterile. In its natural habitat, this species is known to propagate by vegetative multiplication, but sexual reproduction seems to be as important as the vegetative propagation to this species.


Assuntos
Cephaelis/fisiologia , Segregação de Cromossomos/genética , Cromossomos de Plantas/genética , Meiose/fisiologia , Pólen/anatomia & histologia , Meiose/genética , Reprodução/genética , Reprodução/fisiologia
20.
Braz. j. biol ; 66(1a): 151-159, Feb. 2006. ilus, tab, graf
Artigo em Inglês | LILACS | ID: lil-426277

RESUMO

Estudos reprodutivos foram realizados em acessos brasileiros de poaia, Cephaelis ipecacuanha. O comportamento meiótico foi estudado usando a técnica de esmagamento. Foi observada segregação irregular de cromossomos durante meiose I e II, muitos grupos de cromossomos em telófase II, micronúcleos, divisão incorreta do citoplasma, citocinese incompleta e produtos pós-meióticos anômalos, principalmente políades. A média do índice meiótico foi inferior a 72%. A viabilidade polínica foi analisada utilizando-se solução de Alexander e a percentagem de pólen viável variou entre as formas florais, brevistila e longistila (85,3% a 93,1%), e entre as diferentes localidades (82,5% a 92,6%) analisadas. O tamanho do pólen variou entre viáveis e inviáveis, e entre os inviáveis vazios e contraídos. Em seu habitat natural, a poaia apresenta propagação por multiplicação vegetativa, mas a reprodução sexuada parece ser tão importante para essa espécie quanto a propagação vegetativa.


Assuntos
Cephaelis/fisiologia , Segregação de Cromossomos/genética , Cromossomos de Plantas/genética , Meiose/fisiologia , Pólen/anatomia & histologia , Meiose/genética , Reprodução/genética , Reprodução/fisiologia
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