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1.
Molecules ; 28(19)2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37836666

RESUMO

Fluorescent labels are key tools in a wide range of modern scientific applications, such as fluorescence microscopy, flow cytometry, histochemistry, direct and indirect immunochemistry, and fluorescence in situ hybridization (FISH). Small fluorescent labels have important practical advantages as they allow maximizing the fluorescence signal by binding multiple fluorophores to a single biomolecule. At present, the most widely used fluorescent labels available present small Stokes shifts and are too costly to be used in routine applications. In this work we present four new coumarin derivatives, as promising and inexpensive fluorescent labels for biomolecules, obtained through a cost-effective, efficient, and straightforward synthetic strategy. Density functional theory and time-dependent density functional theory calculations of the electronic ground and lowest-lying singlet excited states were carried out in order to gain insights into the observed photophysical properties.


Assuntos
Corantes Fluorescentes , Hibridização in Situ Fluorescente , Análise Custo-Benefício , Corantes Fluorescentes/química
2.
J Appl Toxicol ; 43(2): 323-334, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36000810

RESUMO

3-(3,4-Dihydroxyphenyl)-7,8-dihydroxycoumarin is a newly synthesized coumarin derivative with a potent antioxidant effect. The aim of the present study is to investigate the safety of this compound, determining the in vitro cytotoxic and genotoxic in human peripheral blood mononuclear cells (PBMC) and in HepG2/C3A cells. Cell viability has been investigated by the trypan blue staining test and MTT assay and the genotoxicity by the comet assay and micronucleus test, using concentrations between 0.01 and 10 µg/ml. The compound proved to be noncytotoxic in both cell lines, at all tested concentrations, protecting the cells from the DNA damage. In addition, this molecule does not show clastogenic/aneugenic effects when performing the micronucleus test with cytokinesis blockade. Based on the obtained data, and the conditions of the experiments, we can conclude that the 3-(3,4-dihydroxyphenyl)-7,8-dihydroxycoumarin is a safe molecule up to a concentration of 10 µg/ml, which encourages further studies aiming to explore its potential as a drug candidate.


Assuntos
Leucócitos Mononucleares , Leucócitos , Humanos , Ensaio Cometa , Umbeliferonas/toxicidade , Dano ao DNA , Testes para Micronúcleos , Mutagênicos
3.
Food Saf (Tokyo) ; 10(3): 73-82, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36237397

RESUMO

Hepatotoxicity associated with food-derived coumarin occurs occasionally in humans. We have, herein, assessed the data of existing clinical and nonclinical studies as well as those of in silico models for humans in order to shed more light on this association. The average intakes of food-derived coumarin are estimated to be 1-3 mg/day, while a ten-times higher level is expected in the worst-case scenarios. These levels are close to or above the tolerable daily intake suggested by a chronic study in dogs. The human internal exposure levels were estimated by a physiologically-based pharmacokinetic model with the use of virtual doses of coumarin in the amounts expected to derive from foods. Our results suggest that: (i) coumarin can be cleared rapidly via 7-hydroxylation in humans, and (ii) the plasma levels of coumarin and of its metabolite, o-hydroxyphenylacetic acid associated with hepatotoxicity, are considerably lower than those yielding hepatotoxicity in rats. Pharmacokinetic data suggest a low or negligible concern regarding a coumarin-induced hepatotoxicity in humans exposed to an average intake from foods. Detoxification of coumarin through the 7-hydroxylation, however, might vary among individuals due to genetic polymorphisms in CYP2A6 enzyme. In addition, the CYP1A2- and CYP2E1-mediated activation of coumarin can fluctuate as a result of induction caused by environmental factors. Furthermore, the daily consumption of food-contained coumarin was implicated in the potential risk of hepatotoxicity by the drug-induced liver injury score model developed by the US Food and Drug Administration. These results support the idea of the existence of human subpopulations that are highly sensitive to coumarin; therefore, a more precise risk assessment is needed. The present study also highlights the usefulness of in silico approaches of pharmacokinetics with the liver injury score model as battery components of a risk assessment.

4.
Int J Mol Sci ; 23(11)2022 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-35682998

RESUMO

A novel series of coumarin-thiadiazole hybrids, derived from substituted coumarin-3-carboxylic acids was isolated and fully characterized with the use of a number of spectroscopic techniques and XRD crystallography. Several of the novel compounds showed intensive fluorescence in the visible region, comparable to that of known coumarin-based fluorescence standards. Moreover, the new compounds were tested as potential antineurodegenerative agents via their ability to act as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. Compared to the commercial standards, only a few compounds demonstrated moderate AChE and BuChE activities. Moreover, the novel derivatives were tested for their antimicrobial activity against a panel of pathogenic bacterial and fungal species. Their lack of activity and toxicity across a broad range of biochemical assays, together with the exceptional emission of some hybrid molecules, highlights the possible use of a number of the novel hybrids as potential fluorescence standards or fluorescence imaging agents.


Assuntos
Anti-Infecciosos , Tiadiazóis , Acetilcolinesterase/metabolismo , Anti-Infecciosos/farmacologia , Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Cumarínicos/química , Cumarínicos/farmacologia , Simulação de Acoplamento Molecular , Estrutura Molecular , Análise Espectral , Relação Estrutura-Atividade , Tiadiazóis/farmacologia
5.
Carbohydr Res ; 518: 108597, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35617914

RESUMO

In this paper, a series of target derivatives were synthesized by introducing coumarin into inulin structure using three-step chemical modification, and their structures were characterized by FTIR, 1H NMR, and 13C NMR. At the same time, the antioxidant activities of inulin derivatives were determined, including DPPH-radical scavenging activity, superoxide-radical scavenging activity, PTIO-radical scavenging activity and reducing ability. The test results showed that the antioxidant activities of inulin derivatives containing coumarin were significantly increased. Especially, inulin derivatives showed excellent DPPH radical-scavenging ability (IC50 0.09-0.11 mg/mL). Meanwhile, the scavenging ability of PTIO-radical was increased by more than 80%, and the IC50 values were all between 0.23 and 0.26 mg/mL. At the concentration below 1 mg/mL, the scavenging rate of all inulin derivatives could even reach 100%. This study provides a feasible way to synthesize inulin derivatives with significant activity, which may be developed into new antioxidants in medicine and cosmetics.


Assuntos
Antioxidantes , Inulina , Antioxidantes/química , Antioxidantes/farmacologia , Cumarínicos/química , Cumarínicos/farmacologia , Sequestradores de Radicais Livres/química , Inulina/química
6.
Chem Biol Drug Des ; 98(5): 894-902, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34453501

RESUMO

Catalyzed peroxidation of unsaturated lipid in animals and plants intimately is linked to the activity of 15-Lipoxygenase enzymes. Lipoxygenases (LOXs) are well known to play an important role in many acute and chronic syndromes such as inflammation, asthma, cancer, and allergy. In this study, a series of mono prenyloxycarbostyrils were synthesized and evaluated as potential inhibitors of soybean 15-Lipoxygenase (SLO) and their inhibitory potencies were compared to mono prenyloxycoumarins which had been reported in the previous works. The synthetic compounds inhibit lipoxygenase enzyme by competitive mechanism like the prenyloxy coumarins. The results showed that position and length of the prenyl moiety play the important role in lipoxygenase inhibitory activity. Among all of the synthetic compounds (coumarin and carbostyril derivatives), 5-farnesyloxycoumarin and 8-farnesyloxycarbostyril demonstrated the best inhibitory activity by IC50  values of 1.1 µM and 0.53 µM, respectively.


Assuntos
Araquidonato 15-Lipoxigenase/metabolismo , Hidroxiquinolinas/síntese química , Inibidores de Lipoxigenase/síntese química , Quinolonas/síntese química , Compostos de Bifenilo/química , Cumarínicos/química , Humanos , Hidroxiquinolinas/farmacologia , Inibidores de Lipoxigenase/farmacologia , Picratos/química , Quinolonas/farmacologia , Glycine max/enzimologia , Relação Estrutura-Atividade
7.
J Enzyme Inhib Med Chem ; 35(1): 1442-1449, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32614678

RESUMO

Coumarins are widely diffused secondary metabolites possessing a plethora of biological activities. It has been established that coumarins represent a peculiar class of human carbonic anhydrase (hCA) inhibitors having a distinct mechanism of action involving a non-classical binding with amino acid residues paving the entrance of hCA catalytic site. Herein, we report the synthesis of a small series of new coumarin derivatives 7-11, 15, 17 prepared via classical Pechmann condensation starting from resorcinol derivatives and suitable ß-ketoesters. The evaluation of inhibitory activity revealed that these compounds possessed nanomolar affinity and high selectivity towards tumour-associated hCA IX and XII over cytosolic hCA I and hCA II isoforms. To investigate the binding mode of these new coumarin-inspired inhibitors, the most active compounds 10 and 17 were docked within hCA XII catalytic cleft.


Assuntos
Anidrase Carbônica IX/antagonistas & inibidores , Inibidores da Anidrase Carbônica/farmacologia , Anidrases Carbônicas/metabolismo , Simulação de Acoplamento Molecular , Neoplasias/enzimologia , Umbeliferonas/farmacologia , Antígenos de Neoplasias/metabolismo , Anidrase Carbônica IX/metabolismo , Inibidores da Anidrase Carbônica/síntese química , Inibidores da Anidrase Carbônica/química , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Umbeliferonas/síntese química , Umbeliferonas/química
8.
Sensors (Basel) ; 20(3)2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-32046240

RESUMO

Detection of an environmental contaminant requires the use of expensive measurement equipment, which limits the realization of in situ tests because of their high cost, their limited portability, or the extended time duration of the tests. This paper presents in detail the development of a portable low-cost spectrophotometer which, by using a specialized chemosensor, allows detection of mercuric ions (Hg2+), providing effective and accurate results. Design specifications for all the stages assembling the spectrophotometer and the elements selected to build them are presented along with the process to synthesize the chemosensor and the tests developed to validate its performance in comparison with a high-precision commercial laboratory spectrophotometer.

9.
Turk J Chem ; 44(4): 1148-1163, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33488219

RESUMO

A fluorogenic probe based on a coumarin-derivative for Cu2+ sensing in CH3CN/H2O media (v/v, 95/5, 5.0 µM) was developed and applied in real samples. 3-(4-chlorophenyl)-6,7-dihydroxy-coumarin (MCPC) probe was obtained by synthetic methodologies and identified by spectral techniques. The probe MCPC showed remarkable changes with a "turn-off" fluorogenic sensing approach for the monitoring of Cu2+ at 456 nm under an excitation wavelength of 366 nm. The response time of the probe MCPC was founded as only 1 min. The detection limit of the probe MCPC was recorded to be 1.47 nM. The binding constant and possible stoichiometric ratio (1:1) values were determined by Benesi-Hildebrand and Job's plot systems, respectively. The mechanism of the probe MCPC with Cu2+ was further confirmed by ESI-MS and FT-IR analyses, as well as supported by theoretical calculations. Furthermore, the probe MCPC was successfully employed for the practical applications to sense Cu2+ in different herbal and black tea samples. The proposed sensing method was also verified by ICP-OES method.

10.
Appl Radiat Isot ; 151: 265-273, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31228735

RESUMO

Combination of the calculation of reactivity descriptors and the cold iodine test for some coumarin derivatives was used in order to optimize the radioiodination reaction. The strongly nucleophilic predicted coumarins were subjected to the action of cold iodine. With two coumarins substituted at 3 by the 2-hydroxybenzoyl group, iodination did not occur but a product of intramolecular heterocyclization was obtained. This strategy is useful for economic and environmentally friendly radioiodination.


Assuntos
Custos e Análise de Custo , Cumarínicos/química , Radioisótopos do Iodo/química , Cromatografia Líquida de Alta Pressão , Ciclização , Espectrofotometria Ultravioleta
11.
Front Pharmacol ; 9: 992, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30233371

RESUMO

Epilepsy is a brain disorder characterized by sudden recurrent seizures. Considering the fact that epileptogenesis is a process that affects the quality of life, our goal is to delay the process of epileptogenesis and to increase the latency of epileptic attacks, offering better quality of life to patients. Traditional system of medicines has a promise in some of the medicines, which have been used for the treatment of epilepsy. One such medicinal plant is Eclipta alba (EA). According to Ayurvedic philosophy, the juice of leaves of EA is pounded with garlic and pepper for the treatment of epilepsy. Taking clue from the Ayurvedic system of medicines, we formulated coumarin fraction of EA, namely, coumarin nasal formulation (CNF) for its nasal delivery. CNF was analyzed by using high performance liquid chromatography (HPLC) and ultraviolet absorption spectroscopy for its drug content determination. In vitro drug release studies were performed in simulated nasal electrolyte solution (SNES) maintaining constant pH of 5.5 at 37°C. Irritation by CNF was evaluated using hen's egg test chorioallantoic membrane (HET-CAM) assay. Formulation was found to be non-irritant in HET-CAM assay. CNF was further assessed in vivo by measuring the progress and attainment of pentylenetetrazole (PTZ) kindling in mice. Neuronal changes were assessed by hematoxylin and eosin (H&E) and Nissl staining technique. Glial fibrillary acidic protein (GFAP) a neuroinflammatory marker and tumor necrosis factor alpha (TNF-α) an inflammatory marker were also measured. CNF (10 mg/kg, nasal route) when given as a pretreatment lowered seizure score and delayed the progression of seizure similar to diazepam. CNF decreased the PTZ induced oxidative damage, TNF-α as well as GFAP levels in the midbrain tissue particularly in hippocampus region. The results suggest that CNF may be a promising therapeutic approach to offer protection from sudden recurrent seizures alone or in combination with current drugs in management of epilepsy.

12.
Drug Metab Pharmacokinet ; 33(1): 82-89, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29342418

RESUMO

Cytochrome P450 2A13 (CYP2A13) is responsible for the metabolism of chemical compounds such as nicotine, coumarin, and tobacco-specific nitrosamine. Several of these compounds have been recognized as procarcinogens activated by CYP2A13. We recently showed that CYP2A13*2 contributes to inter-individual variations observed in bladder cancer susceptibility because CYP2A13*2 might cause a decrease in enzymatic activity. Other CYP2A13 allelic variants may also affect cancer susceptibility. In this study, we performed an in vitro analysis of the wild-type enzyme (CYP2A13.1) and 8 CYP2A13 allelic variants, using nicotine and coumarin as representative CYP2A13 substrates. These CYP2A13 variant proteins were heterologously expressed in 293FT cells, and the kinetic parameters of nicotine C-oxidation and coumarin 7-hydroxylation were estimated. The quantities of CYP2A13 holoenzymes in microsomal fractions extracted from 293FT cells were determined by measuring reduced carbon monoxide-difference spectra. The kinetic parameters for CYP2A13.3, CYP2A13.4, and CYP2A13.10 could not be determined because of low metabolite concentrations. Five other CYP2A13 variants (CYP2A13.2, CYP2A13.5, CYP2A13.6, CYP2A13.8, and CYP2A13.9) showed markedly reduced enzymatic activity toward both substrates. These findings provide insights into the mechanism underlying inter-individual differences observed in genotoxicity and cancer susceptibility.


Assuntos
Alelos , Hidrocarboneto de Aril Hidroxilases/genética , Cumarínicos/metabolismo , Variação Genética/genética , Imidazóis/metabolismo , Nicotina/metabolismo , Hidrocarboneto de Aril Hidroxilases/química , Células HEK293 , Humanos , Hidroxilação , Oxirredução , Estrutura Secundária de Proteína
13.
Thromb Res ; 157: 126-133, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28738274

RESUMO

Over the last decade, the coagulation factor XIIa (FXIIa) has seen renewed interest as a therapeutic target. Indeed, its inhibition could offer a protection against thrombosis without increasing the risk of bleeding. Moreover, it could answer the need for a safe prevention of blood-contacting medical devices-related thrombosis. Among the FXII and FXIIa inhibitors already described in literature, organic small-molecular-weight inhibitors are rather left behind. In this study, we were focused on the discovery and assessment of water soluble small molecules. First, a search within our library of compounds flagged two promising hits. Indeed, enzymes and plasma assays suggested they have a greater activity on the contact factors (FXIa, plasma kallikrein and FXIIa) than on the TF pathway. Then, simple pharmacomodulations were undertaken with the aim to design more selective FXIIa inhibitors. This afforded compounds having different degrees of selectivity. All compounds were finally screened in whole blood using an 8-channel microfluidic model and thromboelastometry measurements. Interestingly, all molecules interfered with the thrombus formation and one of them could be considered as a small organic contact inhibitor.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Cumarínicos/uso terapêutico , Cumarínicos/farmacologia , Humanos
14.
Eur J Med Chem ; 107: 219-32, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26588065

RESUMO

A series of fused tricyclic coumarin derivatives bearing iminopyran ring connected to various amido moieties were developed as potential multifunctional anti-Alzheimer agents for their cholinesterase inhibitory and radical scavenging activities. In vitro studies revealed that most of these compounds exhibited high inhibitory activity on acetylcholinesterase (AChE), with IC50 values ranging from 0.003 to 0.357 µM which is 2-220 folds more potent than the positive control, galantamine. Their inhibition selectivity against AChE over butyrylcholinesterase (BuChE) has increased about 194 fold compared with galantamine. The developed compounds also showed potent ABTS radical scavenging activity (IC50 7.98-15.99 µM). Specifically, the most potent AChE inhibitor 6n (IC50 0.003 ± 0.0007 µM) has an excellent antioxidant profile as determined by the ABTS method (IC50 7.98 ± 0.77 µM). Moreover, cell viability studies in SK N SH cells showed that the compounds 6m-q have significant neuroprotective effects against H2O2-induced cell death, and are not neurotoxic at all concentrations except 6n and 6q. The kinetic analysis of compound 6n proved that it is a mixed-type inhibitor for EeAChE (Ki1 0.0103 µM and Ki2 0.0193 µM). Accordingly, the molecular modeling study demonstrated that 6m-q with substituted benzyl amido moiety possessed an optimal docking pose with interactions at catalytic active site (CAS) and peripheral anionic site (PAS) of AChE simultaneously and thereby they might prevent aggregation of Aß induced by AChE. Furthermore, in silico ADMET prediction studies indicated that these compounds satisfied all the characteristics of CNS acting drugs. Most active inhibitor 6n is permeable to BBB as determined in the in vivo brain AChE activity. To sum up, the multipotent therapuetic profile of these novel tricyclic coumarins makes them promising leads for developing anti-Alzheimer agents.


Assuntos
Cumarínicos/química , Cumarínicos/farmacologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Sítios de Ligação , Butirilcolinesterase/metabolismo , Técnicas de Química Sintética , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Simulação por Computador , Cumarínicos/síntese química , Avaliação Pré-Clínica de Medicamentos/métodos , Galantamina/farmacologia , Humanos , Peróxido de Hidrogênio/toxicidade , Masculino , Camundongos Endogâmicos BALB C , Modelos Moleculares , Fármacos Neuroprotetores/síntese química , Síndromes Neurotóxicas/etiologia
15.
Expert Opin Drug Metab Toxicol ; 11(1): 67-79, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25345887

RESUMO

INTRODUCTION: Coumarin vitamin K antagonists are the mainstay of anticoagulant therapy in atrial fibrillation, prosthetic heart valves and thromboembolic conditions. Concerns with these drugs include large inter-individual variability in dose requirements, narrow therapeutic index and need to monitor prothrombin time repeatedly. AREAS COVERED: Pharmacogenetic studies and dosing algorithms for warfarin and phenprocoumon. EXPERT OPINION: Gene candidate studies in Brazilian patients verified consistently the association of warfarin and pheprocoumon stable dose requirements with CYP2C9 and VKORC1 polymorphisms, and minor or no influence of other pharmacogenes (e.g., CYP4F2 and F7). The predictive power of warfarin and phenprocoumon dosing algorithms developed for Brazilians compares favorably with those reported for other populations. A warfarin dosing algorithm derived for an admixed cohort performed equally well in self-reported White and Black patients, in marked contrast with the considerably poorer performance of other warfarin algorithms in patients of African descent compared to those of European ancestry. This discrepancy is ascribed to the extensive European/African admixture among Brazilians. Prospective studies of clinical utility of coumarin dosing algorithms, in the context of the Brazilian Public Health System, would represent an important counterpart to recently published trials in European and North American cohorts with predominant or exclusive European ancestry.


Assuntos
Anticoagulantes/farmacologia , Cumarínicos/farmacologia , Etnicidade/genética , Farmacogenética/métodos , Anticoagulantes/efeitos adversos , Brasil/etnologia , Cumarínicos/efeitos adversos , Etnicidade/etnologia , Humanos , Polimorfismo Genético/efeitos dos fármacos , Polimorfismo Genético/genética
16.
Toxicol Rep ; 2: 268-274, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-28962359

RESUMO

6,7-Dihydroxycoumarin (6,7-HC) (aesculetin) is a natural and synthetic coumarin derivative of great interest for use by humans due to their potent antioxidant properties. Considering that there are no reports that assess the in vivo genetic toxicity of 6,7-HC, the aim of the present study was to investigate its genotoxic potential in terms of DNA damage in peripheral blood, liver, bone marrow and testicular cells of Swiss albino mice by the comet assay, and its clastogenic/aneugenic potential in bone marrow cells using the micronucleus test. In addition, the ability of 6,7-HC to modulate the genotoxic effects induced by doxorubicin (DXR) was also preliminarily evaluated. Cytotoxicity was assessed by scoring polychromatic (PCE) and normochromatic (NCE) erythrocytes' ratio. The test compound was administered orally at doses of 25, 50 and 500 mg kg-1 isolated and also simultaneously to DXR (80 mg kg-1). The results showed that 6,7-HC did not induce significant DNA damage in any of the analyzed cells, and also did not show any significant increase in micronucleated PCE at the three tested doses. The PCE/NCE ratio indicated no cytotoxicity. Moreover, the extent of DNA damage induced by DXR decreased significantly only in peripheral blood and testicular cells, and only at the lowest dose of 6,7-HC.

17.
J Ethnopharmacol ; 155(2): 1353-61, 2014 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-25068578

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The roots of Angelica decursiva Fr. Et Sav (Umbelliferae) have been frequently used in traditional medicine as anti-inflammatory, antitussive, analgesic agents and expectorant, especially for treating cough, asthma, bronchitis and upper respiratory tract infections. To establish the scientific rationale for the clinical use of Angelica decursiva and to identify new agents for treating inflammatory lung disorders, pharmacological evaluation of the roots of Angelica decursiva and the isolated constituents was performed. METHODS: In vitro study was carried out using two lung cells, lung epithelial cells (A549) and alveolar macrophages (MH-S). The inflammatory markers such as IL-6 and nitric oxide (NO) for each cell line were examined. For in vivo study, a mouse model of lipopolysaccharide (LPS)-induced acute lung injury was used and the effects on lung inflammation were established by measuring the cell numbers in bronchoalveolar lavage fluid (BALF) and by histological observation. RESULTS: Water and 70% ethanol extracts of the roots of Angelica decursiva showed considerable inhibitory activity against LPS-induced lung inflammation in mice following oral administration at a dose of 400 mg/kg. Five coumarin derivatives including columbianadin, umbelliferone, umbelliferone 6-carboxylic acid, nodakenin and nodakenetin were isolated. Among the isolated compounds, columbianadin was found to possess strong inhibitory activity against the inflammatory response of IL-1ß-treated A549 cells and LPS-treated MH-S cells. Columbianadin was found to inhibit NO production by down-regulation of inducible NO synthase. Moreover, columbianadin was also proved to possess significant inhibitory activity against LPS-induced lung inflammation following oral administration at a dose of 20-60 mg/kg. CONCLUSIONS: The roots of Angelica decursiva were proved to be effective in the treatment of lung inflammation. Columbianadin can be a potential new agent for treating inflammatory lung disorders.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Angelica , Anti-Inflamatórios/farmacologia , Cumarínicos/farmacologia , Pulmão/efeitos dos fármacos , Macrófagos Alveolares/efeitos dos fármacos , Extratos Vegetais/farmacologia , Raízes de Plantas , Pneumonia/tratamento farmacológico , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/metabolismo , Angelica/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular Tumoral , Cumarínicos/química , Cumarínicos/isolamento & purificação , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Endotoxinas , Etanol/química , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-6/metabolismo , Pulmão/imunologia , Pulmão/metabolismo , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/metabolismo , Masculino , Camundongos Endogâmicos ICR , Óxido Nítrico/imunologia , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/metabolismo , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química , Plantas Medicinais , Pneumonia/induzido quimicamente , Pneumonia/imunologia , Pneumonia/metabolismo , Solventes/química , Fatores de Tempo , Água/química
18.
Rev. cuba. plantas med ; 18(4): 543-554, oct.-dic. 2013.
Artigo em Inglês | LILACS | ID: lil-695050

RESUMO

Introducción: Justicia pectoralis Jacq. (Acanthaceae) es una especie medicinal nativa de la América tropical. En Cuba es usada en la medicina tradicional en el tratamiento de afecciones nerviosas. La industria farmacéutica cubana trabaja en el desarrollo de procesos tecnológicos para la obtención de materias primas de calidad farmacéutica a partir de productos naturales. Objetivo: desarrollar un proceso tecnológico para la obtención de extractos secos a partir de extractos acuosos de Justicia pectoralis. Métodos: se desarrolló un proceso para la obtención de extracto seco por spray drying a partir de extracto acuoso de Justicia pectoralis. La influencia que sobre el contenido de cumarina tenían la relación sólido-líquido y el tiempo de extracción fue estudiada aplicando un diseño superficie respuesta. Se estudió el proceso de secado y la posterior evaluación farmacológica del polvo seco. Resultados: estos mostraron que la relación sólido-líquido tenía una fuerte influencia estadísticamente significativa sobre la extracción de la cumarina en las condiciones de trabajo experimentadas. El tiempo de extracción y la interacción entre ambos factores no fueron significativos para el modelo de regresión estudiado. Por otro lado, la evaluación de la influencia de aditivos inertes en el proceso de secado mostró que los mejores rendimientos se alcanzaban cuando se empleaba almidón soluble 30 por ciento, y no se afectaba la actividad sedante del producto. Conclusiones: una relación sólido-líquido de 1:20 y un tiempo de extracción de 15 min resultaron las condiciones óptimas para la extracción de cumarina


Introduction: Justicia pectoralis Jacq. (Acanthaceae), is a medicinal species native to the American tropics. In Cuba it is used in folk medicine in the treatment of nervous disorders. The Cuban Pharmaceutical Industry is working on the development of technological processes for the obtention of pharmaceutical quality raw materials from natural products.Objectives: develop a technological process to obtain dry extract from aqueous extracts of J. pectoralis.Methods: a process to obtain dry extract by spray drying from aqueous extract of J. pectoralis was developed. The influence of solid-liquid r ratio and extraction time on coumarin content was evaluated by applying a response surface methodology (RSM). The drying process and later pharmacological evaluation of the dry powder were studied. Results: results show that solid-liquid ratio was the statistically significant main effect, having a strong positive influence on coumarin extraction in our working conditions. Extraction time and interaction between both factors were not significant for regression models. On the other hand, evaluation of the influence of inert additives on drying s showed that the best results were obtained with the use of 30 percent soluble starch, which did not affect sedative activity. Conclusions: a solid-liquid ratio of 1:20 and an extraction time of 15 minutes were suggested as optimum parameters for coumarin extraction


Assuntos
Cumarínicos , Avaliação de Medicamentos , Extratos Vegetais , Tranquilizantes
19.
Artigo em Inglês | MEDLINE | ID: mdl-23832227

RESUMO

This paper deals with the use of some natural pigments as well as synthetic dyes to act as sensitizers in dye-sensitized solar cells (DSSCs). Anthocyanin dye extracted from rosella (Hibiscus sabdariffa L.) flowers, the commercially available textile dye Remazole Red RB-133 (RR) and merocyanin-like dye based on 7-methyl coumarin are tested. The photostability of the three dyes is investigated under UV-Vis light exposure. The results show a relatively high stability of the three dyes. Moreover, the photostability of the solid dyes is studied over the TiO2 film electrodes. A very low decolorization rates are recorded as; rate constants k=1.6, 2.1 and 1.9×10(-3)min(-1) for anthocyanin, RR and coumarin dyes, respectively. The stability results favor selecting anthocyanin as a promising sensitizer candidate in DSSCs based on natural products. Dyes-sensitized solar cells are fabricated and their conversion efficiency (η) is 0.27%, 0.14% and 0.001% for the anthocyanin, RR and coumarin dyes, respectively. Moreover, stability tests of the sealed cells based on anthocyanin and RR dyes are done under continuous light exposure of 100mWcm(-2), reveals highly stable DSSCs.


Assuntos
Corantes/química , Corantes/economia , Luz , Energia Solar/economia , Absorção , Antocianinas/química , Antocianinas/economia , Cor , Custos e Análise de Custo , Cumarínicos/química , Cumarínicos/economia , Eletrodos , Cinética , Microscopia Eletrônica de Transmissão , Titânio/química , Difração de Raios X
20.
Rev. bras. plantas med ; Rev. bras. plantas med;14(spe): 159-162, 2012. ilus, tab
Artigo em Português | LILACS | ID: lil-648541

RESUMO

Este estudo objetivou avaliar a resposta do crescimento e do metabolismo secundário de Justicia pectoralis, expresso em produção de cumarina, a crescentes dinamizações de A. montana. O experimento foi conduzido na Universidade Federal de Viçosa. O delineamento estatístico foi inteiramente casualizado, com seis repetições e cinco tratamentos, totalizando 30 parcelas experimentais, sendo cada parcela constituída de uma planta por vaso. Os tratamentos foram as dinamizações 3CH, 30CH, 60CH, 100CH e 200CH do preparado homeopático A. montana. Os tratamentos foram aplicados às plantas via pulverização, em intervalos semanais, iniciando logo após o plantio. Após quatro meses do plantio as plantas foram colhidas. As características de crescimento avaliadas foram matérias fresca e seca de folhas e caules, matérias fresca e seca de inflorescências e matérias fresca e seca total. No estudo fitoquímico foi avaliada a produção da cumarina (1-2 benzopirona). Não houve resposta nas variáveis de crescimento aos tratamentos. As dinamizações de A. montana causaram alterações no metabolismo secundário das plantas. Os conteúdos de cumarina das plantas com A. montana 3CH e 30CH foram próximos e mais baixos, aumentando progressivamente a partir de 60CH, chegando ao máximo em 100CH, seguido de redução em 200CH. A preparação homeopática A. montana causa alterações no metabolismo secundário de chambá, sendo as repostas dependentes da dinamização.


Were evaluated the responses to dynamizations of Arnica montana in the growth and in the secondary metabolism of Justicia pectoralis expressed as coumarin production. The studies were carried out at the Universidade Federal de Viçosa. The statistical design was completely randomized, with six replicates and five treatments, 30 experimental plots, one plant per pot. The treatments were dynamizations 3CH, 30CH, 60CH, 100CH and 200CH homeopathic preparation of A. montana. The application the treatments begun are planting seedlings, the aerial part being sprayed, at weekly intervals. After four months of planting, the plants were harvested. The evaluated growth characteristics were: fresh and dry matter of leaves and stems, fresh and dry matter of inflorecenses, and fresh and dry matter total. In the phytochemistry study, the production of the coumarin 1,2-benzopyrone was evaluated. Were no responses of growth characteristics. The dynamizations of A. montana caused changes in secondary metabolism of plants. The coumarin production with A. montana plants 3CH and 30CH were lower, increasing progressively from 60CH, and coming to increased in 100CH, followed by a large reduction in the 200CH. The homeopathic preparation A. montana cause change in secondary metabolism of chambá, and the responses depend on dynamizations.


Assuntos
Justiça Social/metabolismo , Metabolismo Secundário/fisiologia , Arnica/crescimento & desenvolvimento , Cumarínicos/efeitos adversos , Homeopatia
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