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1.
J Nat Med ; 73(3): 648-652, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30963375

RESUMO

A new crinine-type alkaloid crijaponine A (1), a new galanthamine-type alkaloid crijaponine B (2), and 11 known alkaloids-ungeremine (3), lycorine (4), 2-O-acetyllycorine (5), 1, 2-O-diacetyllycorine (6), (-)-crinine (7), 11-hydroxyvittatine (8), hamayne (9), (+)-epibuphanisine (10), crinamine (11), yemenine A (12), and epinorgalanthamine (13)-were isolated from the rhizome and fruits of Crinum asiaticum var. japonicum. The structural elucidation of the isolated compounds was performed by spectroscopic methods including 2D NMR. The isolated compounds were evaluated for cytotoxicity against HeLa and HL-60 cells lines and were tested for acetylcholinesterase inhibition activity.


Assuntos
Alcaloides/química , Crinum/química , Frutas/química , Extratos Vegetais/química , Rizoma/química , Humanos , Estrutura Molecular
2.
Fitoterapia ; 130: 48-53, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30114468

RESUMO

Four novel and potently bioactive Amaryllidaceae alkaloids, 4,8-dimethoxy-cripowellin C (1), 4,8-dimethoxy-cripowellin D (2), 9-methoxy-cripowellin B (3), and 4-methoxy-8-hydroxy-cripowellin B (4), together with one known alkaloid, cripowellin C (5) were isolated from the 95% EtOH extract of the bulbs of Crinum latifolium. Structural elucidation of all the compounds were performed by spectral methods such as 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR as well as spectroscopy high resolution mass spectrometry. All isolates were in vitro evaluated for their cytotoxic activity against seven lung cancer cell lines, in addition to antimicrobial activity for eight bacteria, scavenging potential using ABTS·+ and DPPH test, and anti-inflammatory activity for Cox-1 and Cox-2 which had not previously been tested for crinane-type alkaloids with the cleavage between C-1 and C-13. Consequently, alkaloids 1-5 exhibited potent cytotoxicity against all of seven tested tumor cell lines with (IC50 < 30 nM). Alkaloids 3 and 4 displayed the significant antimicrobial activity with IC50 values <0.50 mM and antioxidant activity in the ABTS·+ and DPPH test. Additionally, Alkaloids 1-5 exhibited comparable inhibition of Cox-1 (>64%) and Cox-2 (>90%) with positive control.


Assuntos
Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Crinum/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Linhagem Celular Tumoral , China , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Raízes de Plantas/química
3.
J Chromatogr A ; 1567: 99-110, 2018 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-30033169

RESUMO

An undisputed trend in sample preparation at present is to meet the requirements of green chemistry especially in the field of natural products. Green technology continuously pursues new solvents to replace common organic solvents that possess inherent toxicity. Over the past two decades, non-ionic surfactants have gained enormous attention from the scientific community. The micelle-mediated extraction and cloud-point preconcentration (CPE) methods offer a convenient alternative to the conventional extraction systems. Recently, natural deep eutectic solvents (NDESs) have emerged as green and sustainable solvents for efficient extraction of bioactive compounds or drugs. They are generally composed of neutral, acidic or basic compounds that form liquids of high viscosity when mixed in certain molar ratio. The presented work aimed to comprehensively compare and evaluate the potential and effectiveness of NDES as well as non-ionic surfactants (Genapol X-080, Triton X-100 and Triton X-114) for extraction of Amaryllidaceae alkaloids from Crinum powellii bulbs as representative example of plant material, in comparison to the conventional solvents (methanol, ethanol and water).A new validated high-performance thin-layer chromatographic (HPTLC) method has been developed for the simultaneous quantitation of three alkaloids markers, lycorine, crinine and crinamine, in the bulbs of C. powellii. Extraction efficiency of the targeted alkaloids from the bulb matrix with organic and ecofriendly (green) solvents were studied. Results revealed that NDES and surfactants were significantly more efficient in alkaloid extraction than previous methods requiring the consumption of organic solvents and water. Genapol X-80 demonstrated 138%, 149% and 145%, while choline chloride: fructose (5:2): H2O (35%) NDES mixture demonstrated 243%, 225% and 238% of the total alkaloidal extraction capacity of ethanol, methanol and water, respectively at 50 °C for extraction time 1 h using ultrasonication for all experiments. Furthermore, Box-Behnken response surface design combined with the overall desirability value were successfully employed to optimize and study the individual and interactive effect of process variables such as extraction temperature, time and surfactant %, for Genapol X-80, and sonication extraction temperature, time and water concentration, for choline chloride: fructose: H2O NDES mixture, on the alkaloidal yield from C. powellii. It was evident that parameters interacting together can act in synergism if adjusted properly according to the optimized conditions to obtain maximum alkaloids extractability. It is for the first time that the efficiency of micelle-mediated extraction has been compared to that of natural deep eutectic solvents for the extraction of alkaloids and the results thoroughly discussed.


Assuntos
Alcaloides de Amaryllidaceae/isolamento & purificação , Cromatografia em Camada Delgada , Química Verde/métodos , Solventes/química , Alcaloides/química , Alcaloides de Amaryllidaceae/análise , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Crinum/química , Fenantridinas/análise , Fenantridinas/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Tensoativos/química , Água/química
4.
Molecules ; 23(6)2018 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-29861456

RESUMO

Natural products play an important role in the development of new drugs. In this context, the Amaryllidaceae alkaloids have attracted considerable attention in view of their unique structural features and various biological activities. In this study, twenty-three alkaloids were identified from Crinum amabile by GC-MS and two new structures (augustine N-oxide and buphanisine N-oxide) were structurally elucidated by NMR. Anti-parasitic and cholinesterase (AChE and BuChE) inhibitory activities of six alkaloids isolated from this species, including the two new compounds, are described herein. None of the alkaloids isolated from C. amabile gave better results than the reference drugs, so it was possible to conclude that the N-oxide group does not increase their therapeutic potential.


Assuntos
Alcaloides/química , Crinum/química , Óxidos/química , Alcaloides/farmacologia , Alcaloides de Amaryllidaceae/química , Alcaloides de Amaryllidaceae/farmacologia , Antiprotozoários/química , Antiprotozoários/farmacologia , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Compostos Fitoquímicos , Extratos Vegetais/química
5.
Bioorg Med Chem ; 25(15): 4203-4211, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28648491

RESUMO

Antiplasmodial bioassay guided fractionation of a Madagascar collection of Crinum firmifolium led to the isolation of seven compounds. Five of the seven compounds were determined to be 2-alkylquinolin-4(1H)-ones with varying side chains. Compounds 1 and 4 were determined to be known compounds with reported antiplasmodial activities, while 5 was believed to be a new branched 2-alkylquinolin-4(1H)-one, however, it was isolated in limited quantities and in admixture and therefore was synthesized to confirm its structure as a new antiplasmodial compound. Along with 5, two other new and branched compounds 6 and 7 were synthesized as well. Accompanying the five quinolones were two known compounds 2 and 3 which are inactive against Plasmodium falciparum. The isolation, structure elucidation, total synthesis, and biological evaluation of these compounds are discussed in this article.


Assuntos
Antimaláricos/química , Antimaláricos/isolamento & purificação , Crinum/química , Plasmodium falciparum/efeitos dos fármacos , Quinolonas/química , Quinolonas/isolamento & purificação , Antimaláricos/síntese química , Espectrometria de Massas , Espectroscopia de Prótons por Ressonância Magnética , Quinolonas/síntese química , Espectrofotometria Ultravioleta
6.
J Sep Sci ; 40(5): 1150-1157, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28044411

RESUMO

A molecularly imprinted nanoshell on the surface of silica nanospheres was prepared for specific enrichment and identification of alkaloids from Crinum asiaticum L. var. sinicum. The nanoshell was synthesized by surface polymerization using lycorine as the template, acrylamide as the functional monomer, ethylene glycol dimethacrylate as the cross-linker, 2',2-azobisisobutyronitrile as the initiator and acetonitrile as the pore-forming agent. The core-shell nanospheres were characterized by transmission electron microscopy and infrared spectroscopy, and the results show that the nanoshell layer was homogeneously attached to the surface of vinyl-modified SiO2 nanospheres. The adsorption capacity of the nanospheres was estimated by binding equilibrium and adsorption kinetics experiments. The maximum adsorption amount of lycorine on the nanospheres was 6.68 µmol/g and the imprinting factor was nearly 2.5, indicating a good imprinting effect. The nanospheres were successfully applied in solid-phase extraction for lycorine from Crinum asaticum L. var. sinicum and detection of target molecule in rat metabolites. The average recoveries of lycorine in Crinum asaticum L. var. sinicum extraction and rat metabolites were 93.5 ± 0.6% (n = 3) and 91.6 ± 1.9% (n = 3), respectively. This work provides a simple approach for the fabrication of a molecularly imprinted nanoshell at the surface of silica nanospheres-based solid-phase extraction for drug analysis.


Assuntos
Alcaloides/isolamento & purificação , Crinum/química , Impressão Molecular , Nanosferas , Extração em Fase Sólida , Adsorção , Animais , Nanoconchas , Polímeros , Ratos , Dióxido de Silício
7.
J Ethnopharmacol ; 194: 421-433, 2016 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-27725241

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The leaf extract of Crinum jagus L. (Amaryllidaceae) is widely used in traditional Cameroonian medicine as antiepileptic remedy and for the treatment of convulsion, depression and mood disorders associated with epilepsy. AIM OF THE STUDY: Hence, this study was conducted to evaluate the effects of an active fraction extracted from the leaves of Crinum jagus against seizures, depression-like behaviour and oxidative stress in pentylenetetrazole (PTZ)-induced kindling in mice. MATERIALS AND METHODS: Bioactive-guided fractionation of the leaf extract of Crinum jagus by using 70mg/kg PTZ-induced convulsions in mice, afforded a potent anticonvulsant fraction (flavonol kaempferol; C4.4). The effects of C4.4 on 30mg/kg PTZ-induced kindling, kindling-induced depression like-behaviour and oxidative stress was evaluated. Mice were injected PTZ (30mg/kg, i.p.) once every alternate day (48±1h) until the development of kindling. Depression was assessed using tail suspension test and forced swim test while the oxidative stress parameters were estimated in the whole brain at the end of experiments. Mice were submitted to the rota-rod task and open-field test in order to assess any non-specific muscle-relaxant or sedative effects of C4.4. Acute toxicity of C4.4 was also assessed in mice. RESULTS: Convulsions-induced by 70mg/kg PTZ were strongly antagonized by C4.4. Oral administration of C4.4 significantly increased the latency to myoclonic jerks, clonic seizures as well as generalized tonic-clonic seizures, improved the seizure mean stage and decreased the number of myoclonic jerks in PTZ-kindled mice. The data indicated also that C4.4 significantly reduced the immobility times in the tail suspension test and the forced swim test. This active fraction has also antioxidant properties by decreasing the lipid peroxidation, and augmenting endogenous antioxidant enzymes in brain. C4.4 administered (12.5-50mg/kg) did not alter the locomotion of animals in the open-field or rotarod tests, which suggest a lack of a central depressant effect. The animals did not exhibit any acute toxicity to C4.4 at the therapeutic doses. CONCLUSION: These results suggest that pretreatment with C4.4 ameliorates convulsions-induced by PTZ, protects mice against kindling development, depression-like behaviour and oxidative stress in PTZ-kindled mice. These finding provides scientific rationale for the use of Crinum jagus extracts for the amelioration of epilepsy observed in traditional medicine in Cameroon.


Assuntos
Anticonvulsivantes/farmacologia , Crinum/química , Depressão/prevenção & controle , Modelos Animais de Doenças , Excitação Neurológica/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Pentilenotetrazol/toxicidade , Extratos Vegetais/farmacologia , Convulsões/prevenção & controle , Animais , Masculino , Camundongos , Folhas de Planta/química
8.
Bioorg Med Chem ; 24(21): 5418-5422, 2016 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-27624525

RESUMO

Antimalarial bioassay-guided fractionation of the swamp lily Crinum erubescens led to the isolation of four compounds with potent antiplasmodial activity. Compounds 1 and 2 were determined from their spectroscopic data to be the known pesticidal compound cripowellin A and the known pesticidal and antiproliferative compound cripowellin B. 1D and 2D-NMR techniques were used to determine the identities of 3 and 4 as the new compounds cripowellin C and D. A fifth compound was identified as the known alkaloid hippadine, which was inactive against Plasmodium falciparum. The antiplasmodial IC50 values of compounds 1-4 were determined to be 30±2, 180±20, 26±2, and 260±20nM, respectively, and their antiproliferative IC50 values against the A2780 human ovarian cancer cell line were 11.1±0.4, 16.4±0.1, 25±2, and 28±1nM.


Assuntos
Alcaloides/farmacologia , Antimaláricos/farmacologia , Crinum/química , Plasmodium falciparum/efeitos dos fármacos , Alcaloides/química , Alcaloides/isolamento & purificação , Antimaláricos/química , Antimaláricos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Testes de Sensibilidade Parasitária , Relação Estrutura-Atividade
9.
Biomed Pharmacother ; 82: 35-43, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27470336

RESUMO

This study determined the anti-obesity effect of Crinum asiaticum var. japonicum Baker extract (CAE) on adipocytes and obese mice. The inhibitory effects of CAE on adipocyte differentiation and adipogenesis were determined using differentiation induction medium in 3T3-L1 cells. To get an insight into underlying molecular actions of CAE, we investigated the changes in the expression levels of genes involved in lipogenesis by CAE treatment using qRT-PCR. CAE strongly suppressed adipocyte differentiation through downregulation of PPARγ, C/EBPα, C/EBP ß, and aP2. CAE treatment could also suppress the expression levels of ACC, FAS, LPL and HMGCR gene in 3T3-L1 cells. Male C57BL/6 strain and C57BL/6J-ob/ob strain mice were fed with HFD containing 60% fat and normal diet in the presence or absence of 25, 50, and 100mg/kg CAE for 7 weeks. CAE supplementation could highly suppress the body weight gain and epididymal fat accumulation without changes in food uptake in both obese models. Increases in total cholesterol, LDL-cholesterol and triglyceride were highly suppressed in the presence of CAE. In summary, CAE has an anti-obesity effect and this anti-obesity potential might be associated with downregulation of genes involved in adipocyte differentiation and lipogenesis.


Assuntos
Crinum/química , Dieta Hiperlipídica/efeitos adversos , Obesidade/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipogenia/efeitos dos fármacos , Adipogenia/genética , Animais , Peso Corporal/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Modelos Animais de Doenças , Comportamento Alimentar/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Gotículas Lipídicas/metabolismo , Lipídeos/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/sangue , Obesidade/patologia , Tamanho do Órgão/efeitos dos fármacos , PPAR gama/metabolismo , Fitoterapia , Extratos Vegetais/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Transcrição/metabolismo , Ganho de Peso/efeitos dos fármacos
10.
Anal Chim Acta ; 932: 60-8, 2016 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-27286770

RESUMO

The current widely utilized polymer or C8, C18 end-capped material-based sorbents for solid-phase extraction could not capture alkaloids well only based on "like dissolves like" principle. In this paper, a layer-by-layer functionalized porous Zinc sulfide nanospheres-based solid-phase extraction (SPE) combined with liquid chromatography time-of-flight/mass spectrometry (LC-TOF/MS) and gas chromatography-mass spectrometry (GC-MS) was developed for the specific enrichment and identification of alkaloids from complex matrixes, Crinum asiaticum var. sinicum crude extracts. The functionalized porous Zinc sulfide nanospheres were prepared by the amidation reaction of poly-(acrylic acid) (PAA) homopolymer with amino groups onto the porous ZnS nanospheres. Tandem LC-TOF/MS spectrometry presented that the almost all of the twenty-three main peaks in elution fraction from the SPE could be inferred as alkaloids with ion of mass according to the nitrogen rule and hit formula with Peak View1.2@software from AB SCIEX, and seven alkaloids including two new found chemical entities were directly identified from their GC-MS spectra and retention indices. We believe that this SPE protocol can also be utilized in the future to selectively enrich alkaloids from extracts of other plant species.


Assuntos
Alcaloides/química , Alcaloides/isolamento & purificação , Crinum/química , Cromatografia Gasosa-Espectrometria de Massas/métodos , Nanosferas/química , Extração em Fase Sólida/métodos , Sulfetos/química , Compostos de Zinco/química , Porosidade
11.
J Nat Med ; 69(4): 538-42, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26026497

RESUMO

The inhibition of the hedgehog (Hh) signaling pathway has emerged as an attractive anti-cancer strategy. As part of our continuing search for natural inhibitors of the Hh/GLI1 signaling pathway, we isolated three alkaloids (1-3) from Crinum asiaticum. Compounds 1 and 3 showed potent Hh/GLI1-mediated transcriptional inhibitory activity and exhibited cytotoxicity against human pancreatic (PANC1) and prostate (DU145) cancer cells. Our data revealed that compounds 1 and 3 clearly inhibited the Hh signaling pathway by down-regulating the expression of GLI-related proteins (PTCH and BCL2) in DU145 cells.


Assuntos
Crinum/química , Proteínas Hedgehog/química , Plantas Medicinais/química , Fatores de Transcrição/química , Regulação para Baixo , Humanos , Transdução de Sinais , Ativação Transcricional , Proteína GLI1 em Dedos de Zinco
12.
J Ethnopharmacol ; 158 Pt A: 123-31, 2014 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-25456427

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Hippadine is an alkaloid isolated from Crinum macowanii. Crinum macowanii is used in South Africa to treat oedema, 'heart disease', rheumatic fever, cancer and skin diseases, and belongs to the plant family Amaryllidaceae, assumed to have originated in the South African region. The aim of this study was to evaluate the effect of hippadine, an alkaloid extracted from Crinum macowanii, on the blood pressure (BP) and heart rate (HR) in anaesthetized male spontaneously hypertensive Wistar rats (SHR); and to find out if α1 and⧸or ß1 adrenoceptors contribute to its effects. MATERIALS AND METHODS: Hippadine (2.5-12.5mg/kg), adrenaline (0.05-0.20mg/kg), atenolol (0.5-40mg/kg) and prazosin hydrochloride (100-500µg/kg) were infused intravenously, and the BP and HR measured via a pressure transducer connecting the femoral artery and the PowerLab. Adrenaline increased the systolic, diastolic and mean arterial BP, while hippadine, atenolol and prazosin respectively decreased the systolic, diastolic and mean arterial BP. Increases in HR were observed with both adrenaline and prazosin, while reductions in HR were observed with atenolol and hippadine. Infusion of adrenaline in rats pre-treated with atenolol (30mg/kg), prazosin (400µg/kg), and hippadine (10mg/kg) led to similar increases in BP and HR in all groups. All changes in HR or BP were significant (p<0.05) and dose dependent. CONCLUSION: Hippadine decreases the BP and HR in SHR, and these effects may be due to α1 and ß1 adrenoceptor inhibition.


Assuntos
Alcaloides de Amaryllidaceae/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Crinum/química , Frequência Cardíaca/efeitos dos fármacos , Alcaloides de Amaryllidaceae/administração & dosagem , Alcaloides de Amaryllidaceae/isolamento & purificação , Animais , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/isolamento & purificação , Anti-Hipertensivos/farmacologia , Atenolol/administração & dosagem , Atenolol/farmacologia , Relação Dose-Resposta a Droga , Epinefrina/administração & dosagem , Epinefrina/farmacologia , Hipertensão/tratamento farmacológico , Masculino , Medicina Tradicional Africana , Prazosina/administração & dosagem , Prazosina/farmacologia , Ratos , Ratos Endogâmicos SHR , Ratos Wistar , África do Sul
13.
Nat Prod Res ; 28(10): 704-10, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24444026

RESUMO

In the search for novel antibacterial agents against multidrug-resistant bacteria, an alkaloid extract obtained from whole plants of Crinum angustum Steud., containing six different groups of alkaloids, was analysed by using gas chromatography/mass spectrometry, and its in vitro activity against American Type Culture Collection bacterial strains and clinical isolates was evaluated. The antimicrobial activity of the extract was tested against nine standard strains of microorganisms and two drug-resistant clinical isolates, methicillin-resistant Staphylococcus aureus and carbapenemase-producing Klebsiella pneumoniae. The extract exhibited a significant activity against six of the examined strains of microorganisms. Antibacterial activity was more pronounced on Gram-positive bacteria than on Gram-negative bacteria, and IC50 values ranged from 156 to 625 µg/mL. Mycostatic activity against Candida albicans was also found, with an IC50 of 78 µg/mL after 48 h of incubation . Promising results were also obtained from tests carried out on both clinical isolates investigated.


Assuntos
Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Antifúngicos/isolamento & purificação , Antifúngicos/farmacologia , Crinum/química , Alcaloides/química , Antibacterianos/química , Antifúngicos/química , Proteínas de Bactérias/metabolismo , Candida albicans/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Concentração Inibidora 50 , Itália , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/enzimologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , beta-Lactamases/metabolismo
14.
J Ethnopharmacol ; 149(1): 75-83, 2013 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-23769983

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Crinum latifolium L. (CL) leaf extracts have been traditionally used in Vietnam and are now used all over the world for the treatment of prostate cancer. However, the precise cellular mechanisms of the action of CL extracts remain unclear. AIM OF THE STUDY: To examine the effects of CL samples on the anti-tumour activity of peritoneal murine macrophages. MATERIALS AND METHODS: The properties of three extracts (aqueous, flavonoid, alkaloid), one fraction (alkaloid), and one pure compound (6-hydroxycrinamidine) obtained from CL, were studied (i) for redox capacities (DPPH and bleaching beta-carotene assays), (ii) on murine peritoneal macrophages (MTT assay) and on lymphoma EL4-luc2 cells (luciferine assay) for cytotoxicity, (iii) on macrophage polarization (production of ROS and gene expression by PCR), and (iv) on the tumoricidal functions of murine peritoneal macrophages (lymphoma cytotoxicity by co-culture with syngeneic macrophages). RESULTS: The total flavonoid extract with a high antioxidant activity (IC50=107.36 mg/L, DPPH assay) showed an inhibitory action on cancer cells. Alkaloid extracts inhibited the proliferation of lymphoma cells either by directly acting on tumour cells or by activating of the tumoricidal functions of syngeneic macrophages. The aqueous extract induced mRNA expression of tumour necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin 6 (IL-6) indicating differentiation of macrophages into pro-inflammatory M1 polarized macrophages. The total flavonoid, alkaloid extracts and an alkaloid fraction induced the expression of the formyl peptide receptor (FPR) on the surface of the polarized macrophages that could lead to the activation of macrophages towards the M1 phenotype. Aqueous and flavonoid extracts enhanced NADPH quinine oxido-reductase 1 (NQO1) mRNA expression in polarized macrophages which could play an important role in cancer chemoprevention. All the samples studied were non-toxic to normal living cells and the pure alkaloid tested, 6-hydroxycrinamidine, was not active in any of the models investigated. CONCLUSIONS: Our results indicate that CL extracts and alkaloid fraction (but not pure 6-hydroxycrinamidine) inhibit the proliferation of lymphoma cells in multiple pathways. Our results are in accordance with traditional usage and encourage further studies and in vivo assays.


Assuntos
Alcaloides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Crinum/química , Etnofarmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Extratos Vegetais/farmacologia , Alcaloides/isolamento & purificação , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Cocultura , Crinum/crescimento & desenvolvimento , Humanos , Macrófagos Peritoneais/citologia , Macrófagos Peritoneais/imunologia , Medicina Tradicional do Leste Asiático , Camundongos , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Espécies Reativas de Oxigênio/metabolismo , Vietnã
15.
Niger J Physiol Sci ; 28(2): 135-40, 2013 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-24937387

RESUMO

Tuberculosis (TB) is of great public health burden globally especially in developing countries of Africa and Asia . Current TB regimen involves multiple therapies and of long duration leading to poor patient adherence. There is also the challenge of multidrug resistant TB. Hence, there is a need for discovery of new anti- TB drugs. This study was designed to investigate the in -vitro activity of the crude methanolic extract and chromatographic fractions of the bulb of Crinum jagus against Mycobacterium tuberculosis isolates. The extracts were screened for anti- TB activity against three different M. tuberculosis isolates and a drug susceptible reference strain H37Rv using Lowenstein Jensen (L-J) medium and Middlebrook 7H10agar. The crude extract was prepared using soxhlet extraction apparatus while the purified fractions were obtained by column chromatography. The two media were inoculated with M. tuberculosis strains, after which the crude and purified extracts were added. After 4-6 weeks incubation, colony forming units were counted and percentage inhibition calculated. The crude extract and the purified fractions showed inhibitory activity on all the isolates tested including the reference strain. Fraction 3 showed the highest inhibitory percentage (86%) among the extracts. At a concentration of 1.0mg/ml, the percentage inhibition of fraction 3, rifampicin and isoniazid against M. tuberculosis strain 3 were 83%, 95% and 86% in L-J medium respectively while 86%, 96% and 89% were obtained respectively in Middle brook medium. Results showed that the crude methanolic extract and the purified fractions of the bulb of Crinum jagus exhibited anti-mycobacterial activity which is an indication of promising potential of this plant for the development of anti-tuberculosis agent.


Assuntos
Antituberculosos/farmacologia , Crinum , Metanol/química , Mycobacterium tuberculosis/efeitos dos fármacos , Extratos Vegetais/farmacologia , Solventes/química , Antituberculosos/química , Antituberculosos/isolamento & purificação , Cromatografia em Camada Delgada , Contagem de Colônia Microbiana , Crinum/química , Relação Dose-Resposta a Droga , Mycobacterium tuberculosis/crescimento & desenvolvimento , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Raízes de Plantas , Plantas Medicinais
16.
Chem Pharm Bull (Tokyo) ; 59(12): 1545-8, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22130378

RESUMO

Two new alkaloids (1, 2) were isolated from the whole plants of Crinum asiaticum var. sinicum together with seven known alkaloids. The structures of the new alkaloids were elucidated by spectroscopic analyses and chemical conversions from known alkaloids. New alkaloid 1 was isolated for the first time as a natural product, although it has been prepared as a synthetic product.


Assuntos
Alcaloides/química , Crinum/química , Extratos Vegetais/química , Alcaloides/isolamento & purificação , Oxirredução , Extratos Vegetais/isolamento & purificação , Análise Espectral
17.
Blood Cells Mol Dis ; 47(2): 129-32, 2011 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-21742519

RESUMO

Several anticoagulants, anti-platelet and thrombolytic medications are used for the treatment of thrombotic disorders. Anti-coagulants and anti-platelet agents prevent the formation of blood clots but do not dissolve existing clots, whereas thrombolytic agents are able to dissolve a clot but emboli can form even after successful treatment. Thus, none of them provide a permanent and complete solution. In this regard a single molecule that could both dissolve the clot and prevent the formation of new clots would be useful in the treatment of thrombotic diseases. Crinumin, a stable and active (in many adverse conditions) serine protease, shows plasmin-like fibrinolytic activity and inhibits platelet aggregation and P-selectin exposure, as established by photography, phase contrast microscopy, whole blood optical Lumi-aggregometry and flow cytometry. Crinumin could be an efficient and inexpensive therapeutic agent for the treatment and prevention of thromboembolic diseases.


Assuntos
Anticoagulantes/farmacologia , Plaquetas/metabolismo , Crinum/química , Fibrinolíticos/farmacologia , Proteínas de Plantas/farmacologia , Ativação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Tromboembolia , Trombose , Anticoagulantes/isolamento & purificação , Anticoagulantes/uso terapêutico , Plaquetas/citologia , Cromatografia por Troca Iônica , Relação Dose-Resposta a Droga , Eletroforese em Gel de Poliacrilamida , Fibrinólise/efeitos dos fármacos , Fibrinolíticos/isolamento & purificação , Fibrinolíticos/uso terapêutico , Citometria de Fluxo , Humanos , Selectina-P/análise , Selectina-P/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Proteínas de Plantas/isolamento & purificação , Proteínas de Plantas/uso terapêutico , Tromboembolia/sangue , Tromboembolia/tratamento farmacológico , Tromboembolia/patologia , Tromboembolia/prevenção & controle , Trombose/sangue , Trombose/tratamento farmacológico , Trombose/patologia , Trombose/prevenção & controle
18.
Phytother Res ; 25(11): 1686-92, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21442675

RESUMO

Crinum zeylanicum is used in folk medicine as a rubefacient in rheumatism, a treatment for malaria or as a poison. Complex alkaloid profiles in C. zeylanicum plant organs were revealed by GC-MS analysis, including several bioactive compounds. Crinine, lycorine, 11-O-acetoxyambelline, ambelline, 6-hydroxybuphanidrine and 6-ethoxybuphanidrine (an artefact of the isolation procedure) were isolated. Crinine, 6-hydroxybuphanidrine and 6-ethoxybuphanidrine showed antiproliferative effects against human tumor cell lines, crinine being the most active (IC50 14.04 µM against HL-60/Dox). The latter compound induced apoptosis in a dose-dependent manner in HL-60 and MDA-MB-231 cell lines. Structure-activity relationships in the studied molecules indicated that the hydrogenation of the double bond at C1-C2 leads to a loss of activity, whereas substitutions at C6, C8 and C11 affect their cytotoxicity.


Assuntos
Alcaloides de Amaryllidaceae/farmacologia , Apoptose/efeitos dos fármacos , Crinum/química , Alcaloides de Amaryllidaceae/isolamento & purificação , Cromatografia Gasosa-Espectrometria de Massas , Células HL-60/efeitos dos fármacos , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
19.
J Nat Prod ; 74(3): 411-9, 2011 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-21314165

RESUMO

A comprehensive study of the alkaloids presentin the leaves of Crinum asiaticum var. sinicum, assisted by HPLC-SPE-NMR, led to the characterization of 21 compounds of similar polarity on an analytical scale. Thirteen of these were isolated for further structural confirmation. Seven are proved to be new, namely, (+)-siculine (4), 1-epijosephinine (11), 7-methoxycrinamabine (10), 2-O-acetylcrinamabine (16), 3-O-acetyl-8-O-demethylmaritidine (17), 2-O-acetylbulbisine (18), and 1-O-acetylbulbisine (19). In addition, dihydrovittatine (6) and 8-O-demethyloxomaritidine (21) were isolated for the first time from Nature, although they have been prepared previously as synthetic products. Their structures were established by spectroscopic analysis.


Assuntos
Alcaloides/isolamento & purificação , Crinum/química , Alcaloides/química , Cromatografia Líquida de Alta Pressão , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Folhas de Planta/química , Estereoisomerismo
20.
Chem Biodivers ; 6(10): 1751-7, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19842135

RESUMO

A phytochemical investigation of the bulbs of Crinum asiaticum L. var. sinicum Baker resulted in the isolation of two new alkaloids, asiaticumines A and B (1 and 2, resp.), together with 21 known compounds, including nine alkaloids, four amides, five phenolic compounds, and three flavonoids. All 23 compounds were isolated for the first time from Crinum asiaticum L. var. sinicum Baker. Their structures were elucidated by spectroscopic methods. In addition, ten alkaloids, 1-10, were evaluated for their cytotoxic activities against human tumor cell lines A549, LOVO, HL-60, and 6T-CEM. Compounds 3, 4, and 7-10 selectively showed remarkable inhibition against one or more of the tested cell lines.


Assuntos
Alcaloides/química , Alcaloides/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Crinum/química , Flavonoides/química , Flavonoides/farmacologia , Alcaloides/isolamento & purificação , Alcaloides/toxicidade , Amidas/química , Amidas/isolamento & purificação , Amidas/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/toxicidade , Linhagem Celular Tumoral , Flavonoides/isolamento & purificação , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Fenóis/química , Fenóis/isolamento & purificação , Fenóis/farmacologia , Extratos Vegetais/química , Análise Espectral
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