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1.
Phytochemistry ; 178: 112458, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32888670

RESUMO

Six previously undescribed tropane alkaloids, designated as erythrobezerrines A-F, were isolated from the EtOH extract from the stem bark of Erythroxylum bezerrae Plowman. Their structures were elucidated based on the interpretation of the NMR and MS data and in some instances, confirmed by X-ray diffraction analysis. The cytotoxicity of the isolated compounds was evaluated against the cancer cell lines L929, PC-3, HCT-116, SNB-19 and NCI-H460, but only erythrobezerrine C showed moderate activity with IC50 values of 3.38 and 5.43 µM for HCT-116 and NCI-H460, respectively.


Assuntos
Erythroxylaceae , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Casca de Planta , Tropanos
2.
Zootaxa ; 4604(1): zootaxa.4604.1.5, 2019 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-31717204

RESUMO

Vallissiana universitaria Pereira Arévalo, a new genus and species of leaf-miner moth (Gracillariidae: Gracillariinae) is described and illustrated with the aid of optical and scanning electron microscopy, including adults, larva, pupa and the mine. Its monophyletic status is confirmed within the subfamily based on a DNA barcode CoI tree. The immature stages are associated with Erythroxylum argentinum O. E. Schulz (Erythroxylaceae) and four larval instars are found, all forming a round blotch mine from the beginning of ontogeny. The first two instars are sap-feeders, using only the epidermal cells, whereas the last two are tissue-feeders, mining the parenchyma cells. Pupation occurs inside the leaf mine within a flimsy, silk-made cocoon. This is the third endemic genus of gracillariid moths described from the Atlantic Forest of Brazil and the first associated with Erythroxylum P. Browne. Characteristics found on the forewing and in the last abdominal segments of the adult were determinant for the proposition of the new genus. The CoI tree indicated that it is closely related to Aspilapteryx, while this genus was recovered as polyphyletic in the analyses. Morphological evidence supports this polyphyly. Consequently, Sabulopteryx Triberti, 1985, stat. nov. is considered a valid genus.


Assuntos
Erythroxylaceae , Lepidópteros , Mariposas , Animais , Brasil , Florestas , Larva
3.
Molecules ; 24(20)2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31640255

RESUMO

The genus Erythroxylum contains species used by indigenous people of South America long before the domestication of plants. Two species, E. coca and E. novogranatense, have been utilized for thousands of years specifically for their tropane alkaloid content. While abuse of the narcotic cocaine has impacted society on many levels, these species and their wild relatives contain untapped resources for the benefit of mankind in the form of foods, pharmaceuticals, phytotherapeutic products, and other high-value plant-derived metabolites. In this review, we describe the current state of knowledge of members within the genus and the recent advances in the realm of molecular biology and biochemistry.


Assuntos
Erythroxylaceae/química , Extratos Vegetais/química , Animais , Erythroxylaceae/classificação , Humanos , Filogenia , Extratos Vegetais/farmacologia , América do Sul
4.
Molecules ; 24(4)2019 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-30813289

RESUMO

Tropane alkaloids (TA) are valuable secondary plant metabolites which are mostly found in high concentrations in the Solanaceae and Erythroxylaceae families. The TAs, which are characterized by their unique bicyclic tropane ring system, can be divided into three major groups: hyoscyamine and scopolamine, cocaine and calystegines. Although all TAs have the same basic structure, they differ immensely in their biological, chemical and pharmacological properties. Scopolamine, also known as hyoscine, has the largest legitimate market as a pharmacological agent due to its treatment of nausea, vomiting, motion sickness, as well as smooth muscle spasms while cocaine is the 2nd most frequently consumed illicit drug globally. This review provides a comprehensive overview of TAs, highlighting their structural diversity, use in pharmaceutical therapy from both historical and modern perspectives, natural biosynthesis in planta and emerging production possibilities using tissue culture and microbial biosynthesis of these compounds.


Assuntos
Alcaloides/biossíntese , Alcaloides/farmacologia , Erythroxylaceae/química , Solanaceae/química , Alcaloides/química , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Humanos , Estrutura Molecular , Extratos Vegetais/biossíntese , Extratos Vegetais/farmacologia , Metabolismo Secundário , Tropanos/síntese química , Tropanos/química , Tropanos/farmacologia
5.
Am J Bot ; 106(1): 154-165, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30629286

RESUMO

PREMISE OF THE STUDY: This investigation establishes the first DNA-sequence-based phylogenetic hypothesis of species relationships in the coca family (Erythroxylaceae) and presents its implications for the intrageneric taxonomy and neotropical biogeography of Erythroxylum. We also identify the closest wild relatives and evolutionary relationships of the cultivated coca taxa. METHODS: We focused our phylogenomic inference on the largest taxonomic section in the genus Erythroxylum (Archerythroxylum O.E.Schulz) using concatenation and gene tree reconciliation methods from hybridization-based target capture of 427 genes. KEY RESULTS: We show that neotropical Erythroxylum are monophyletic within the paleotropical lineages, yet Archerythroxylum and all of the other taxonomic sections from which we sampled multiple species lack monophyly. We mapped phytogeographic states onto the tree and found some concordance between these regions and clades. The wild species E. gracilipes and E. cataractarum are most closely related to the cultivated E. coca and E. novogranatense, but relationships within this "coca" clade remain equivocal. CONCLUSIONS: Our results point to the difficulty of morphology-based intrageneric classification in this clade and highlight the importance of integrative taxonomy in future systematic revisions. We can confidently identify E. gracilipes and E. cataractarum as the closest wild relatives of the coca taxa, but understanding the domestication history of this crop will require more thorough phylogeographic analysis.


Assuntos
Domesticação , Erythroxylaceae/genética , Filogenia , Filogeografia , América do Sul
6.
Phytochemistry ; 155: 12-18, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30056276

RESUMO

Stem bark, root bark, and leaf extracts of Erythroxylum pungens were subjected to phytochemical analysis. N,N-dimethyltryptamine (DMT) was isolated and characterized from E. pungens roots. This unprecedented result is remarkable since no indole alkaloid has been previously reported from Erythroxylaceae so far. Eleven known tropane alkaloids were identified by their mass spectra and 3-(2-methylbutyryloxy)tropan-6,7-diol as well as 3-(2-methylbutyryloxy)nortropan-6,7-diol were isolated and characterized based on mass spectrometry, 1H, 13C, COSY, and NOESY NMR analysis. The complete NMR data are reported for the first time. Inverse Structure-based and Ligand-Based virtual screening were carried out to identify possible targets for 3-(2-methylbutyryloxy)tropan-6,7-diol. The level of cytotoxicity of this tropane alkaloid aliphatic ester was discrete with potencies on the order of 0.3-1.0 mg/mL and better results against HeLa (50% cell viability reduction). Otherwise, atropine (0.3 mg/mL), a Solanaceae tropane alkaloid, and DMT (0.5 mg/mL) from E. pungens roots impaired at 50% the cell viability against HeLa, SiHa, PC3, and 786-0. This study stimulates scientific investigation of the impact of edaphoclimatic features in a semi-arid environment on tropane alkaloid biosynthesis.


Assuntos
Alcaloides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Erythroxylaceae/química , Simulação de Acoplamento Molecular , Alcaloides/química , Alcaloides/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
7.
J Sep Sci ; 39(14): 2720-7, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27214755

RESUMO

The absolute configuration of the naturally occurring isomers of 6ß-benzoyloxy-3α-tropanol (1) has been established by the combined use of chiral high-performance liquid chromatography with electronic circular dichroism detection and optical rotation detection. For this purpose (±)-1, prepared in two steps from racemic 6-hydroxytropinone (4), was subjected to chiral high-performance liquid chromatography with electronic circular dichroism and optical rotation detection allowing the online measurement of both chiroptical properties for each enantiomer, which in turn were compared with the corresponding values obtained from density functional theory calculations. In an independent approach, preparative high-performance liquid chromatography separation using an automatic fraction collector, yielded an enantiopure sample of OR (+)-1 whose vibrational circular dichroism spectrum allowed its absolute configuration assignment when the bands in the 1100-950 cm(-1) region were compared with those of the enantiomers of esters derived from 3α,6ß-tropanediol. In addition, an enantiomerically enriched sample of 4, instead of OR (±)-4, was used for the same transformation sequence, whose high-performance liquid chromatography follow-up allowed their spectroscopic correlation. All evidences lead to the OR (+)-(1S,3R,5S,6R) and OR (-)-(1R,3S,5R,6S) absolute configurations, from where it follows that samples of 1 isolated from Knightia strobilina and Erythroxylum zambesiacum have the OR (+)-(1S,3R,5S,6R) absolute configuration, while the sample obtained from E. rotundifolium has the OR (-)-(1R,3S,5R,6S) absolute configuration.


Assuntos
Erythroxylaceae/química , Tropanos/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Dicroísmo Circular , Estrutura Molecular , Estereoisomerismo , Tropanos/química
8.
Braz Dent J ; 27(1): 108-12, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27007356

RESUMO

The mouth and oropharynx cancer is the 6th most common type of cancer in the world. The treatment may involve surgery, chemotherapy and radiotherapy. More than 50% of drugs against cancer were isolated from natural sources, such as Catharanthus roseus and epipodophyllotoxin, isolated from Podophyllum. The biggest challenge is to maximize the control of the disease, while minimizing morbidity and toxicity to the surrounding normal tissues. The Erythroxylum suberosum is a common plant in the Brazilian Cerrado biome and is popularly known as "cabelo-de-negro". The objective of this study was to evaluate the cytotoxic activity of Erythroxylum suberosum plant extracts of the Brazilian Cerrado biome associated with radiotherapy in human cell lines of oral and hypopharynx carcinomas. Cells were treated with aqueous, ethanolic and hexanic extracts of Erythroxylum suberosum and irradiated at 4 Gy, 6 Gy and 8 Gy. Cytotoxicity was evaluated by MTT assay and the absorbance was measured at 570 nm in a Beckman Counter reader. Cisplatin, standard chemotherapy, was used as positive control. The use of Erythroxylum suberosum extracts showed a possible radiosensitizing effect in vitro for head and neck cancer. The cytotoxicity effect in the cell lines was not selective and it is very similar to the effect of standard chemotherapy. The aqueous extract of Erythroxylum suberosum, combined with radiotherapy was the most cytotoxic extract to oral and hypopharynx carcinomas.


Assuntos
Antineoplásicos/uso terapêutico , Erythroxylaceae/química , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Extratos Vegetais/uso terapêutico , Linhagem Celular Tumoral , Terapia Combinada , Humanos
9.
Cell Cycle ; 15(7): 948-56, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26918580

RESUMO

Plant-derived molecules showing antineoplastic effects have recently gained increased attention as potential adjuvants to traditional therapies for various cancers. Cerrado biome in Brazil contains high floral biodiversity, but knowledge about the potential therapeutic effects of compounds derived from that flora is still limited. The present study investigated the antineoplastic activity of Erythroxylum daphnites Mart., a Brazilian native plant from Cerrado biome, in the SCC-9 oral squamous cell carcinoma cell line. Cells were treated with various concentrations of hexane extract of Erythroxylum daphnites leaves (EDH) and assessed for cytotoxicity, proliferation, and apoptosis. Thin layer chromatography was conducted to characterize the substances present in EDH. Our results showed that EDH exerted anti-proliferative effects in SCC-9 cells by stabilizing the cell cycle at G1 phase in association with reduced intracellular levels of cyclins D and E and increased level of p21. EDH also demonstrated pro-apoptotic properties, as shown by an increased expression of caspase-3. Triterpenes were the major constituents of EDH. Our findings demonstrated a cytotoxic effect of EDH against SCC-9 cells in vitro mediated by the restraint of cellular proliferation and induction of apoptosis. Taken together, these findings support EDH constituents as potential therapeutic adjuvants for oral cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose , Carcinoma de Células Escamosas/metabolismo , Erythroxylaceae/química , Pontos de Checagem da Fase G1 do Ciclo Celular , Neoplasias Bucais/metabolismo , Antineoplásicos Fitogênicos/química , Carcinoma de Células Escamosas/patologia , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citotoxinas/química , Citotoxinas/farmacologia , Humanos , Neoplasias Bucais/patologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Triterpenos/química
10.
J Sep Sci ; 39(7): 1273-7, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26888377

RESUMO

Tropane alkaloids are bioactive metabolites with great importance in the pharmaceutical industry and the most important class of natural products found in the Erythroxylum genus. However, these compounds are usually separated by traditional chromatographic techniques, in which the sample is progressively purified in multiple chromatographic steps, resulting in a time- and solvent-consuming procedure. In this work we present the isolation of a novel alkaloid, 6ß,7ß-dibenzoyloxytropan-3α-ol, together with the two known 3α-benzoyloxynortropan-6ß-ol and 3α,6ß-dibenzoyloxytropane alkaloids, directly from the crude alkaloid fraction from the leaves of Erythroxylum subsessile, by using a single run pH-zone-refining counter-current chromatography method. The ethyl acetate/water (1:1, v/v) biphasic solvent system with triethylamine and HCl as retention and eluter agents, respectively, was used to isolate tropane alkaloids for the first time. The structures of the isolated alkaloids were elucidated by spectroscopic methods.


Assuntos
Distribuição Contracorrente/métodos , Erythroxylaceae/química , Folhas de Planta/química , Tropanos/isolamento & purificação , Concentração de Íons de Hidrogênio , Estrutura Molecular , Tropanos/química
11.
Anim Reprod Sci ; 164: 23-30, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26619941

RESUMO

Erythroxylum caatingae Plowman has a myorelaxing effect on smooth muscle tissue. We investigated the effect of the crude ethanolic extract of E. caatingae Plowman (Ec-EtOH) on the contractility of the ovine cervix. In an isometric system, circular strips were subjected to 90mM potassium (K(+)) or 30µM carbamylcholine (CCh)-induced contraction. We then exposed the tissue to cumulative concentrations of Ec-EtOH (1-729 µg/ml). In other bath solutions, the tissues were exposed to l-NG-nitroarginine methyl ester (l-NAME; 100µM), l-NAME (100µM)+l-arginine (300µM), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, ODQ; 5µM), 4-aminopyridine (4-AP; 3mM), tetraethylammonium (TEA; 0.3mM), glybenclamide (1µM), atosiban (10µM) or verapamil (3µM), followed by the addition of Ec-EtOH (1-729 µg/ml). We also evaluated the effect of cervical Ec-EtOH infusion (2mg) on cervical contractility in vivo. Ec-EtOH decreased cervical contractility induced by K(+) or CCh, and 729 µg/ml Ec-EtOH decreased 85.4±5.1% the amplitude of basal contractility in vitro, with an EC50 of 17.9±3.7 µg/ml. This effect of Ec-EtOH was prevented by l-NAME or ODQ. l-arginine impaired the blunting effect of l-NAME on cervical relaxation caused by Ec-EtOH. However, the potassium channel blockers 4-AP, TEA, and glybenclamide did not modify this myorelaxation triggered by Ec-EtOH. Ec-EtOH also decreased acetylcholine-induced contractions in tissue preincubated with verapamil. In addition, Ec-EtOH decreased ovine cervical contractions in vivo. Thus, Ec-EtOH had a relaxant effect on ovine cervical contractions. This may involve the nitric oxide signal, mediated by cGMP cellular transduction, and be related to intracellular calcium sequestration.


Assuntos
Colo do Útero/efeitos dos fármacos , GMP Cíclico/metabolismo , Erythroxylaceae/química , Óxido Nítrico/metabolismo , Extratos Vegetais/farmacologia , Ovinos , Animais , Feminino , Contração Muscular/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Extratos Vegetais/química , Folhas de Planta/química
12.
Clin Oral Investig ; 19(3): 637-46, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25096669

RESUMO

OBJECTIVES: Antineoplastic effects of molecules derived from plants have recently gained increasing attention as an additive to traditional therapies. The aim of this study was to evaluate the cytotoxic activity of plant extracts from the Brazilian Cerrado biome associated with radiotherapy in head and neck carcinoma cells (HNSCC). MATERIALS AND METHODS: Fifteen extracts derived from five Cerrado plants were tested in HNSCC cell lines (SCC-25, SCC-9, FaDu) and keratinocyte cells (HaCat). Cell cytotoxicity of extracts and association extract/radiation (2Gy/min) was assessed by MTT assay. Cisplatin (50 µg/mL) was used as a positive control. Extracts with the major cytotoxic activity were selected and their IC50 concentrations were defined. Apoptosis was assessed using flow cytometric analysis. RESULTS: Ten isolated extracts resulted in moderate cytotoxicity (>20 and ≤ 50 % of viable cells), while three extracts induced severe cytotoxic effects (≤ 20 % of viable cells). Plant extracts treatment improved radiotherapy cytotoxicity in all cell lines. Although plant extracts are not as potent as cisplatin plus radiation, in FaDu cells, seven extracts associated with irradiation showed cytotoxic activity similar or better than the association of cisplatin and radiation. Hexanic extract of Erythroxylum daphinites could induce apoptosis in oral cancer cells; however, necrosis was the prevalent kind of death in FaDu cells treated with hexanic extract of Erythroxylum suberosum. CONCLUSIONS: Pre-treatment of HNSCC cells with the extract derived from Cerrado plants followed by irradiation induced a supra-additive cytotoxic effect. CLINICAL RELEVANCE: This study highlights the potential biological relevance of the Cerrado biome when associated with traditional therapy for cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Brasil , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Erythroxylaceae , Citometria de Fluxo , Humanos , Queratinócitos/efeitos dos fármacos , Medicina Tradicional , Carcinoma de Células Escamosas de Cabeça e Pescoço
13.
Plant Physiol ; 167(1): 89-101, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25406120

RESUMO

The esterification of methylecgonine (2-carbomethoxy-3ß-tropine) with benzoic acid is the final step in the biosynthetic pathway leading to the production of cocaine in Erythoxylum coca. Here we report the identification of a member of the BAHD family of plant acyltransferases as cocaine synthase. The enzyme is capable of producing both cocaine and cinnamoylcocaine via the activated benzoyl- or cinnamoyl-Coenzyme A thioesters, respectively. Cocaine synthase activity is highest in young developing leaves, especially in the palisade parenchyma and spongy mesophyll. These data correlate well with the tissue distribution pattern of cocaine as visualized with antibodies. Matrix-assisted laser-desorption ionization mass spectral imaging revealed that cocaine and cinnamoylcocaine are differently distributed on the upper versus lower leaf surfaces. Our findings provide further evidence that tropane alkaloid biosynthesis in the Erythroxylaceae occurs in the above-ground portions of the plant in contrast with the Solanaceae, in which tropane alkaloid biosynthesis occurs in the roots.


Assuntos
Aciltransferases/metabolismo , Cocaína/biossíntese , Proteínas de Plantas/metabolismo , Catálise , Cocaína/análogos & derivados , Cocaína/análise , Erythroxylaceae/enzimologia , Erythroxylaceae/metabolismo , Células do Mesofilo/enzimologia , Células do Mesofilo/metabolismo , Folhas de Planta/enzimologia , Folhas de Planta/metabolismo , Proteínas de Plantas/química
14.
Nat Prod Commun ; 9(1): 27-30, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24660454

RESUMO

Chiral resolution of (+/-)-3alpha,6beta-dicinnamoyloxytropane (1) and (+/-)-3alpha,6beta-di(1-methyl-1H-pyrrol-2-ylcarbonyloxy)tropane (2), prepared by esterification of (+/-)-3alpha,6beta-tropanediol (3), was achieved using an amylose-derived HPLC stationary phase and normal phase conditions. The corresponding vibrational circular dichroism (VCD) spectra provided the absolute configuration of the enantiomers as (-)-(3R,6R)-1, (+)-(3S,6S)-1, (-)-(3R,6R)-2 and (+)-(3S,6S)-2. In each case, characteristic VCD bands for the absolute configuration determination of the 3alpha,6beta-tropandiol esters were observed. While the absolute configuration of natural 1, previously isolated from Erythroxylum hypericifolium, could not be established due to the lack of literature optical rotation values, that of catuabine E, previously isolated from E. vacciniifolium, is now assigned as (-)-(3R,6R)-2 by comparison with the optical rotation values of the prepared samples and the reported rotation of the natural product.


Assuntos
Cinamatos/química , Erythroxylaceae/química , Tropanos/química , Dicroísmo Circular , Conformação Molecular
15.
Forensic Sci Int ; 237: 30-9, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24561557

RESUMO

Colombian coca farmers have historically cultivated three varieties of coca for cocaine production (Erythroxylum novogranatense var. novogranatense, Erythroxylum novogranatense var. truxillense, and Erythroxylum coca var. ipadu). Within the past 13 years, 15 new cultigens of cocaine-bearing Erythroxylum have been propagated by Colombian coca farmers; each with differing physical characteristics, yet producing cocaine alkaloids at similar levels found in the historical and native varieties. Fifteen new cultigens were collected from throughout Colombia and propagated along with the three historical varieties within an experimental field in Colombia. Five plants/cultigen were randomly selected and examined for alkaloid content to determine their varietal characteristics when compared to the three known varieties. Ten cultigens gave classic Erythroxylum coca var. ipadu alkaloid profiles, four cultigens produced alkaloid profiles consistent with a hybridization of Erythroxylum novogranatense and Erythroxylum coca var. ipadu, while one cultigen gave heterogeneous alkaloid profiles that could not be characterized.


Assuntos
Cocaína/análise , Erythroxylaceae/química , Drogas Ilícitas/análise , Agricultura , Alcaloides/química , Colômbia , Erythroxylaceae/classificação , Ionização de Chama , Humanos , Folhas de Planta/química
16.
Nat Prod Commun ; 9(9): 1245-8, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25918783

RESUMO

Plant secondary metabolites, such as, specifically, alkaloids and terpenes, may present psychoactive properties that modify the function of the central nervous system (CNS) and induce neurotoxicity. Neurotoxicity involves the response of glial cells, mainly astrocytes, which play a fundamental role in the control of homeostasis of the CNS. Some Erythroxylum species are indigenous to the state of Bahia in Brazil. This study investigated the cytotoxic activity of the diterpene AEP-1, extracted from the fruit of E. passerinum in a GL-15 cell line, astrocytic, glial cells model. The effects on cell viability, analyzed by the MTT assay, demonstrated a dose-dependent cytotoxic effect, with maximum effect at 500 µg/mL of AEP-1, and with a reduction of about 40 and 47% on cellular viability after 24 h and 72 h treatment, respectively. Evidence for induction of apoptosis by AEP-1 was first obtained when GL-15 glial cells were incubated with 250 µg/mL AEP-1 causing reniform and/or pyknotic nuclei and apoptotic bodies revealed by chromatin staining with Hoechst 33258. Increase in DNA fragmentation was also observed by comet assays in cells incubated with 500 µg/mL of AEP-1. Moreover, cells exposed to a sub toxic dose of AEP-1 (250 µg/mL) showed significant changes in morphology--contraction of the cytoplasm and expansion of cellular projections--signifying the presence of astrocytic cytoskeletal protein and glial fibrillary acidic protein (GFAP). These findings indicated astrocytic cells as the target for terpene AEP-1 and suggest the involvement of glial cells with psychoactive symptoms observed in humans and animals after consumption of fruits of plants of the genus Erythroxylum.


Assuntos
Astrócitos/citologia , Astrocitoma/fisiopatologia , Diterpenos/farmacologia , Erythroxylaceae/química , Extratos Vegetais/farmacologia , Apoptose/efeitos dos fármacos , Astrócitos/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular , Fragmentação do DNA/efeitos dos fármacos , Humanos , Modelos Biológicos
17.
Asian Pac J Trop Med ; 6(10): 811-6, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23870471

RESUMO

OBJECTIVE: To investigate the cytotoxicity and the genotoxicity of standardized aqueous of dry leaves of Erythroxylum cuneatum (E. cuneatum) in human HepG2 and WRL68 cells. METHODS: The cytotoxicity of E. cuneatum extract was evaluated by both MTS and LDH assays. Genotoxicity study on E. cuneatum extract was assessed by the single cell gel electrophoresis (comet assay). The protective effect of E. cuneatum against menadione-induced cytotoxicity was also investigated. RESULTS: Results from this study showed that E. cuneatum extract exhibited cytotoxic activities towards the cells with IC50 value of (125±12) and (125±14) µg/mL for HepG2 and WRL68 cells respectively, after 72 h incubation period as determined by MTS assay. LDH leakage was detected at (251±19) and (199.5±12.0) µg/mL for HepG2 and WRL68 respectively. Genotoxicity study results showed that treatment with E. cuneatum up to 1 mg/mL did not cause obvious DNA damage in WRL68 and HepG2 cells. Addition of E. cunaetum did not show significant protection towards menadione in WRL68 and HepG2 Cells. CONCLUSIONS: E. cuneatum standardized aqueous extract might be developed in order to establish new pharmacological possibilities for its application.


Assuntos
Citotoxinas/toxicidade , Erythroxylaceae/química , Mutagênicos/toxicidade , Extratos Vegetais/toxicidade , Folhas de Planta/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Células Hep G2 , Humanos
18.
Braz J Biol ; 72(3): 587-94, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22990831

RESUMO

The edge of a forest fragment can be considered a zone of transition between the interior of the fragment and the surrounding habitat matrix. Plants along the edge are more exposed to disturbance and microclimate variation than interior plants, resulting in the so-called edge effect. In this study, we compared leaf area, fluctuating asymmetry and chemical (water, nitrogen and tannins) leaf traits between Erythroxylum tortuosum plants inhabiting the edge with those growing in the interior of a cerrado fragment in Brazil. We also describe the temporal variation in the vegetative and reproductive phenological events of E. tortuosum plants throughout the season. Nitrogen, leaf area and fluctuating asymmetry did not differ between the two plant groups. Young leaves of the edge plants had significantly higher levels of tannins and lower levels of water than those of interior plants. We suggest that differences in leaf chemical concentrations between edge and interior plants may occur due to factors such as light intensity, wind, temperature and leaf age rather than plant stress. With respect to plant phenology, most reproductive events occurred during the spring. Leaf buds and young leaves prevailed during the rainy season. In the dry season, however, the vegetative events decreased due to leaf senescence followed by leaf abscission.


Assuntos
Erythroxylaceae/química , Erythroxylaceae/fisiologia , Nitrogênio/análise , Folhas de Planta/química , Taninos/análise , Árvores , Água/análise , Brasil , Erythroxylaceae/classificação , Estações do Ano
19.
Proc Natl Acad Sci U S A ; 109(26): 10304-9, 2012 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-22665766

RESUMO

The pharmacologically important tropane alkaloids have a scattered distribution among angiosperm families, like many other groups of secondary metabolites. To determine whether tropane alkaloids have evolved repeatedly in different lineages or arise from an ancestral pathway that has been lost in most lines, we investigated the tropinone-reduction step of their biosynthesis. In species of the Solanaceae, which produce compounds such as atropine and scopolamine, this reaction is known to be catalyzed by enzymes of the short-chain dehydrogenase/reductase family. However, in Erythroxylum coca (Erythroxylaceae), which accumulates cocaine and other tropane alkaloids, no proteins of the short-chain dehydrogenase/reductase family were found that could catalyze this reaction. Instead, purification of E. coca tropinone-reduction activity and cloning of the corresponding gene revealed that a protein of the aldo-keto reductase family carries out this reaction in E. coca. This protein, designated methylecgonone reductase, converts methylecgonone to methylecgonine, the penultimate step in cocaine biosynthesis. The protein has highest sequence similarity to other aldo-keto reductases, such as chalcone reductase, an enzyme of flavonoid biosynthesis, and codeinone reductase, an enzyme of morphine alkaloid biosynthesis. Methylecgonone reductase reduces methylecgonone (2-carbomethoxy-3-tropinone) stereospecifically to 2-carbomethoxy-3ß-tropine (methylecgonine), and has its highest activity, protein level, and gene transcript level in young, expanding leaves of E. coca. This enzyme is not found at all in root tissues, which are the site of tropane alkaloid biosynthesis in the Solanaceae. This evidence supports the theory that the ability to produce tropane alkaloids has arisen more than once during the evolution of the angiosperms.


Assuntos
Alcaloides/biossíntese , Erythroxylaceae/metabolismo , Solanaceae/metabolismo , Cromatografia Líquida , Dados de Sequência Molecular
20.
Int J Mol Sci ; 13(4): 4124-40, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22605969

RESUMO

In the study, we have examined the antitumor and antimicrobial activities of the methanol extract, the fractions, a fraction of total alkaloids and two alkaloids isolated from the stem of Erythroxylum caatingae Plowman. All test fractions, except the hexane fractions, showed antimicrobial activity on gram-positive bacteria and fungi. The acetate: methanol (95:5), acetate, chloroform and hexane fractions show the highest cytotoxicity activity against the NCI-H292, HEp-2 and K562 cell lines using MTT. The absence of hemolysis in the erythrocytes of mice was observed in these fractions and 6ß-Benzoyloxy-3α-(3,4,5- trimethoxybenzoyloxy) tropane (catuabine B). Staining with Annexin V-FITC and JC-1 was used to verify the mechanism of action of the compounds of E. caatingae that showed cytotoxicity less than 30 µg/mL in leukemic cells. After 48 h of incubation, we observed that the acetate: methanol (95:5), acetate, and chloroform fractions, as well as the catuabine B, increased in the number of cells in early apoptosis, from 53.0 to 74.8%. An analysis of the potential of the mitochondrial membrane by incorporation of JC-1 showed that most cells during incubation of the acetate: methanol (95:5) and acetate fractions (63.85 and 59.2%) were stained, suggesting the involvement of an intrinsic pathway of apoptosis.


Assuntos
Anti-Infecciosos/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Erythroxylaceae/metabolismo , Caules de Planta/metabolismo , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Animais , Anti-Infecciosos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Descoberta de Drogas , Eritrócitos/efeitos dos fármacos , Feminino , Fungos/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Células Hep G2 , Humanos , Leucemia/tratamento farmacológico , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Membranas Mitocondriais/efeitos dos fármacos , Extratos Vegetais/farmacologia
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