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1.
ACS Appl Mater Interfaces ; 13(33): 39100-39111, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34382406

RESUMO

In this work, a nanoplatform (FeCORM NPs) loaded with an iron-carbonyl complex was constructed. By exploiting chemodynamic therapy (CDT) and immunogenic cell death (ICD)-induced immunotherapy (IMT), the nanoparticles exhibited excellent efficacy against lung metastasis of melanoma in vivo. The iron-carbonyl compound of the nanomaterials could be initiated by both glutathione (GSH) and hydrogen peroxide (H2O2) to release CO and generate ferrous iron through ligand exchange and oxidative destruction pathways. The released CO caused mitochondria damage, whereas the generated ferrous iron led to oxidative stress via the Fenton reaction. On the other hand, the nanomaterials induced ICD-based IMT, which worked jointly with CDT to exhibit excellent effects against lung metastasis of melanoma through a mouse model. This work demonstrated how a nanoplatform, simple and stable but showing excellent efficacy against tumors, could be built using simple building blocks via a self-assembling approach. Importantly, the system took advantage of relatively high levels of GSH and H2O2 in tumors to initiate the therapeutic effects, which rendered the nanoplatform with a capability to differentiate normal cells from tumor cells. In principle, the system has great potential for future clinical applications, not only in the treatment of lung metastasis of melanoma but also in suppressing other types of tumors.


Assuntos
Antineoplásicos/química , Monóxido de Carbono/química , Compostos de Ferro/química , Neoplasias Pulmonares/tratamento farmacológico , Melanoma/metabolismo , Nanopartículas Metálicas/química , Animais , Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Monóxido de Carbono/farmacocinética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desenvolvimento de Medicamentos , Feminino , Glutationa/química , Humanos , Peróxido de Hidrogênio/química , Imunoterapia/métodos , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Endogâmicos BALB C , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/ultraestrutura , Neoplasias Experimentais , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos
2.
ACS Appl Mater Interfaces ; 11(17): 15417-15425, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30964627

RESUMO

The iridium(III)-cyanine complex (IrCy) was fabricated by conjugating an iridium(III) complex to a cyanine dye with an intense near-infrared (NIR) absorption. IrCy complex nanoparticles (NPs) with high water solubility and photostability were prepared by a solvent evaporation-induced self-assembly strategy. Considering their effective photacoustic (PA) imaging and generation of 1O2 property with 808 nm laser irradiation in aqueous solution, PA imaging guided NIR-driven photodynamic therapy in vivo was effectively conducted in the 4T1 xenograft model. We developed a real-time PA imaging methodology to investigate the pharmacokinetics, tumor targeting, and biodistribution of IrCy NPs. Taking advantage of the analysis of the PA signal of the common iliac vein, the blood circulation half-life of IrCy NPs in mice was calculated to be ∼18 h, and the enhanced permeability and retention effect of IrCy NPs offered the maximum targeting property in the tumor at about 24 h. The obvious change of PA imaging signal in kidney and bladder confirmed IrCy NPs should be excreted partially from the urine system, and the PA signal decreased from 12.5× to 2.8× in the liver, and from 28.8× to 9.4× in the spleen also confirmed the hepatic metabolic pathway.


Assuntos
Carbocianinas/química , Complexos de Coordenação/química , Irídio/química , Nanopartículas/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/metabolismo , Complexos de Coordenação/toxicidade , Meia-Vida , Humanos , Lasers , Nanopartículas/metabolismo , Nanopartículas/toxicidade , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Imagem Óptica/métodos , Técnicas Fotoacústicas , Fotoquimioterapia , Oxigênio Singlete/metabolismo , Distribuição Tecidual , Transplante Heterólogo
3.
Chemosphere ; 214: 830-838, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30300841

RESUMO

ZnO nanoparticle toxicity on aquatic organisms has been extensively studied, but its concentration-and time-dependent effects on ecosystem functioning are remain uncertain. Here we assessed the harmful effects of nano-ZnO (10, 100, 1000 mg L-1) on the stream functioning by using a microcosm system simulating poplar leaf decomposition for 50 days. The 100 mg L-1 ZnO nanoparticles had significantly and stably inhibitory effect on the litter decomposition during the exposure period. The inhibition was not detected in the 10 mg L-1 treatment until 43 d. In contrast, the significant and continuous inhibition started to disappear from 43 d in the 1000 mg L-1 treatment. The varied consequences on litter decomposition might be directly affected by the different ZnO nanoparticle homogeneity of the different treatments. ZnO nanoparticles led to significant decreases in pH value of the decomposition environment, which had significant and positive relationships to the activities of dehydrogenase, glycine-aminopeptidase, N-acetylglucosaminidase, and acid phosphatase. Besides, 10 and 1000 mg L-1 ZnO nanoparticles led to lower fungal diversity, which was negatively related to the variability of decomposition. In conclusion, fungal decomposers showed different responses to the different concentrations of ZnO nanoparticle, and ultimately affected the stability of ecosystem functions.


Assuntos
Ecossistema , Poluentes Ambientais/química , Água Doce/química , Nanopartículas/efeitos adversos , Óxido de Zinco/química , Poluentes Ambientais/análise , Nanopartículas/química , Rios
4.
J Agric Food Chem ; 65(4): 993-994, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-28106387

RESUMO

Oleracimine and oleracimine A were isolated from Portulaca oleracea L. and described in the J. Agric. Food Chem, but the alternative structures of the two compounds are proposed on the basis of NMR analyses.


Assuntos
Alcaloides/química , Anti-Inflamatórios/química , Extratos Vegetais/química , Portulaca/química , Alcaloides/farmacologia , Anti-Inflamatórios/farmacologia , Estrutura Molecular , Extratos Vegetais/farmacologia
5.
Braz. J. Pharm. Sci. (Online) ; 53(2): e16093, 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-839470

RESUMO

ABSTRACT Hydroxydihydrobovolide (HDB) was for the first time isolated from Portulaca oleracea L. and then its cytotoxicity against SH-SYTY cells was studied. Moreover, a rapid and sensitive ultra-high performance liquid chromatographic (UHPLC) method with bergapten as internal standard (IS) was developed and validated to investigate the pharmacokinetics of HDB in rats after intravenous and oral administrations of extract (POE). The UHPLC analysis was performed on a Diamonsil C18 analytical column, using acetonitrile-water (35:65, v/v) as the mobile phase with UV detection at 220 nm. The calibration curve was linear over the range of 0.2-25 µg/mL in rat plasma. The average extraction recovery was from 90.1 to 98.9%, and the relative standard deviations (RSDs) of the intra- and inter-day precisions were less than 4.7 and 4.1%, respectively. The results showed that 50 µM HDB had significant cytotoxicity on the SH-SY5Y cells, which was rapidly distributed with a Tmax of 11 min after oral administration and presented a low absolute bioavailability, 4.12%.


Assuntos
Animais , Masculino , Farmacocinética , Portulaca/classificação , Extratos Vegetais/análise , Cromatografia Líquida de Alta Pressão/métodos
6.
J Agric Food Chem ; 64(29): 5837-44, 2016 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-27396870

RESUMO

Three novel carbon skeleton alkaloids, named oleracimine (1), oleracimine A (2), and oleracone A (3), with one novel azulene carbon skeleton compound, oleracone B (4), and one known compound, ß-carboline (5), were first isolated from Portulaca oleracea L. The structures were determined using spectroscopic methods, including one- and two-dimensional nuclear magnetic resonance and high-resolution electrospray ionization time-of-flight mass spectrometry techniques. In addition, oleracimine (1) was used to investigate the anti-inflammatory effects on lipopolysaccharide-stimulated macrophages. The results of enzyme-linked immunosorbent assay, western blot, and real-time polymerase chain reaction showed that oleracimine (1) remarkably inhibited nitric oxide production and could dose-dependently decrease the secretions of interleukin 6, tumor necrosis factor α, nitric oxide, and prostaglandin E2 in cell culture supernatants as well as the mRNA of cyclooxygenase-2 and inducible nitric oxide synthase.


Assuntos
Alcaloides/química , Alcaloides/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Portulaca/química , Alcaloides/isolamento & purificação , Animais , Anti-Inflamatórios/isolamento & purificação , Ciclo-Oxigenase 2/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Estrutura Molecular , Óxido Nítrico/imunologia , Extratos Vegetais/isolamento & purificação , Células RAW 264.7
7.
J Pharm Pharmacol ; 68(3): 397-405, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26888212

RESUMO

OBJECTIVES: This study was to elucidate the pharmacokinetics of a novel alkaloid, 6-acetyl-2,2,5-trimethyl-2,3-dihydrocyclohepta[b]pyrrol-8(1H)-one, named oleracone isolated from Portulaca oleracea L., and to examine the anti-inflammatory ability with lipopolysaccharide (LPS) stimulated macrophages. METHODS: The novel alkaloid, oleracone, was isolated from Portulaca oleracea L., and its structure was determined by spectroscopic analysis including HRESIMS, 2D NMR spectroscopic data and single-crystal X-ray diffraction. The activity of anti-inflammation was assayed via the test with RAW 264.7 activated by LPS, and the pharmacokinetics of oleracone in rat plasma after intravenous and oral administration at dose of 2.5 mg/kg was, respectively, investigated by a rapid and sensitive ultra high-performance liquid chromatography (UHPLC) method with bergapten as internal standard. KEY FINDINGS: Oleracone was a novel alkaloid first isolated from Portulaca oleracea L. and possessed unique structure in natural products, whose anti-inflammatory effecting on nitrite oxide production and several pivotal pro-inflammatory cytokines was found at the concentration of 50 µm, and the pharmacokinetic results indicated that oleracone was rapidly distributed with Tmax of 15.7 min after oral administration and presented a higher oral absolute bioavailability to be 74.91 ± 10.7%. CONCLUSIONS: Oleracone as novel alkaloid presented remarkably anti-inflammatory effect, which was rapid distributed in rat with high bioavailability of 74.91 ± 10.7%.


Assuntos
Alcaloides/farmacologia , Alcaloides/farmacocinética , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/farmacocinética , Extratos Vegetais/farmacologia , Extratos Vegetais/farmacocinética , Portulaca/química , Administração Oral , Animais , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão/métodos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Ratos , Ratos Wistar , Espectrometria de Massas em Tandem/métodos , Difração de Raios X/métodos
8.
Biomed Chromatogr ; 30(2): 111-6, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26031900

RESUMO

Previous research in our laboratory found that the absolute bioavailability of vitexin-2''-O-rhamnoside (VR) was quite low at 4.89%. A rapid and sensitive UHPLC method using hesperidin as an internal standard was therefore developed and validated to investigate the reasons for this by determining VR in rat plasma after administering intravenously, intraportally (5 mg/kg), intraduodenally and intragastrically (40 mg/kg) to the rat model of the hepatic, gastric and intestinal first-pass effects. As only a high intestinal first-pass effect of VR was found, that is, there existed a low bioavailability of VR (2.40%), inhibitors of P-glycoprotein (P-gp) and cytochrome P450 3A (CYP3A), including verapamil, cyclosporin A and midazolam, and absorption enhancers, including bile salts and borneol, combined with VR, were instilled into duodenum to evaluate the effects on bioavailability of VR. The results demonstrated that area under the concentration-time curve (AUC) values of VR slightly increased after administration of verapamil, cyclosporin A and midazolam, indicating that CYP3A and P-gp do not play an important role in the first-pass effect in the intestine. AUC values of VR significantly increased after administering bile salts or borneol, indicating that the low bioavailability of VR was mainly related to its poor absorption in the intestine.


Assuntos
Apigenina/sangue , Apigenina/farmacocinética , Cromatografia Líquida de Alta Pressão/métodos , Animais , Apigenina/administração & dosagem , Área Sob a Curva , Disponibilidade Biológica , Duodeno/irrigação sanguínea , Duodeno/metabolismo , Mucosa Gástrica/metabolismo , Fígado/irrigação sanguínea , Fígado/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Sensibilidade e Especificidade , Estômago/irrigação sanguínea
9.
Braz. j. pharm. sci ; 51(3): 643-651, July-Sept. 2015. tab, graf
Artigo em Inglês | LILACS | ID: lil-766304

RESUMO

The aim of the present study was to investigate the tissue distribution and excretion of five components of Portulaca oleracea L. extract (POE) in rat following oral administration. A rapid, sensitive and specific ultra-high performance liquid chromatography (UHPLC) method with puerarin as the internal standard was used for the quantitative analysis of five components of POE, including caffeic acid (CA), p-coumaric acid (p-CA), ferulic acid (FA), quercitrin (QUER) and hesperidin (HP) in rat tissues including the liver, intestine, stomach, muscle, heart, lung, brain, kidney and spleen, urine and feces. The results show that onlyp-CA and FA were found in nearly all tissues with low cumulative ratios, and CA was higher in the intestine and stomach with a slightly higher cumulative ratio in the urine and feces after 24 h. HP and QUER were found at low levels in the tissues with low cumulative ratios.


O objetivo do presente estudo foi investigar a distribuição tecidual e excreção de cinco componentes de extrato Portulaca oleracea L. (POE) em ratos após administração oral. Um método analítico rápido, sensível e específico para quantificação de cinco componentes de POE (ácido cafeico (CA), ácidop-cumárico (p-CA), ácido ferúlico (FA), quercitrina (QUER) e hesperidina (HP)) por cromatografia líquida de ultra eficiência (UHPLC), empregando puerarina como padrão interno de referência. Os compostos foram quantificados em diferentes tecidos dos animais, sendo eles fígado, intestino, estômago, músculo, coração, pulmão, cérebro, rim e baço, urina e fezes. Os resultados mostraram que apenas p-CA e FA foram encontradas em todos os tecidos com baixas taxas cumulativas e CA apresentou níveis mais altos no intestino e estômago com a taxa cumulativa um pouco mais elevada na urina e nas fezes após 24 h. HP e QUER apresentaram baixas concentrações nos tecidos com baixas taxas cumulativas.


Assuntos
Ratos , Cromatografia Líquida/estatística & dados numéricos , Portulaca/classificação , Ratos , Compostos Fenólicos , Distribuição Tecidual
10.
Biomed Chromatogr ; 28(5): 637-47, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24254959

RESUMO

Hawthorn leaves, a well-known traditional Chinese medicine, have been widely used for treating cardiovascular and fatty liver diseases. The present study aimed to investigate the therapeutic basis treating fatty liver disease by comparing the tissue distribution of six compounds of hawthorn leaf extract (HLE) in fatty liver rats and healthy rats after oral administration at first day, half month and one month, separately. Therefore, a sensitive and specific HPLC method with internal standard was developed and validated to determine chlorogenic acid, vitexin-4''-O-glucoside, vitexin-2''-O-rhamnoside, vitexin, rutin and hyperoside in the tissues including heart, liver, spleen, kidney, stomach and intestine. The results indicated that the six compounds in HLE presented some bioactivity in treating rat fatty liver as the concentrations of the six compounds varied significantly in inter- and intragroup comparisons (healthy and/or fatty liver group).


Assuntos
Crataegus/química , Fígado Gorduroso/tratamento farmacológico , Extratos Vegetais/farmacocinética , Administração Oral , Animais , Humanos , Masculino , Extratos Vegetais/administração & dosagem , Folhas de Planta/química , Ratos , Ratos Wistar , Distribuição Tecidual
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