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1.
Fitoterapia ; 137: 104189, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31158429

RESUMO

Seventeen lignans (1-17) were obtained from the roots of Isatis indigotica (I. indigotica). Among them, isatindigosesquilignans A-C (1-3) were deduced as three undescribed sesquilignans, which possess unusual carbon skeleton of aryltetralin unit connected with a C6-C3 moiety via a five-membered ring of C-3-C-8″-C-7″-O-C-4. Isatindigosesquilignans B and C were determined as the first examples of its glycosides from a natural source and a plausible biosynthetic pathway was proposed. Moreover, all of the isolated lignans were assayed regarding their inhibitory effects on nitric oxide (NO) production in RAW 264.7 cells and compounds 1, 2 and 7 showed inhibitory effects with IC50 values ranging from 19.46 µM to 64.82 µM.


Assuntos
Isatis/química , Lignanas/farmacologia , Macrófagos/efeitos dos fármacos , Óxido Nítrico/metabolismo , Animais , China , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Lignanas/isolamento & purificação , Camundongos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Raízes de Plantas/química , Células RAW 264.7
2.
Phytochemistry ; 163: 89-98, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31035058

RESUMO

The pharmacologically active dichloromethane extracts of dried woad leaves (Isatis tinctoria L.), and the methanol extracts of comparable fresh leaves of the same plants, were analyzed by LC-MSn. The fresh leaf metabolite profile revealed a complex pattern of indolic compounds. Besides the known indigo precursors, isatan A, isatan B and indican, seven previously unreported indole derivatives were characterized: acetylindican, malonylindican, two dioxindole glucosides, dioxindole malonylglucoside, 6-hydroxyindole-3-carboxylic acid 6-O-glucoside and 6-hydroxyindole-3-carboxylic acid glucose ester. The integration of 122 compounds in fresh leaves and of five selected compounds (indoxyl, isatin, indigo, indirubin, and tryptanthrin) in dried leaves, formed the input data for a stepwise modelling procedure generating five predictive linear models. The structure of the predictive models and a cross validation provide evidence that the models could predict well or moderately well the accumulation of the selected lipophilic compounds, and were simple enough to be used in a woad cultivation program. PLS regression models relating each of the five selected dry leaf indolics to the fresh leaf metabolome were then fitted in order to deduct potential precursors and mechanisms leading to the formation of these lipophilic indolics in drying woad leaves. The models suggested glucobrassicin, isatan A and isatan B as the main candidate precursors of these compounds, besides a minor contribution of other fresh leaf indolics, including malonylindican, actylindican and dioxindole malonylglucoside. Dioxindole malonylglucoside was identified here as isatan C. The models further suggested that the accumulation of phenylpropanoid antioxidants in woad leaves has a negative impact on the formation of indoxyl, isatin, indigo, indirubin and tryptanthrin.


Assuntos
Alcaloides Indólicos/metabolismo , Isatis/química , Folhas de Planta/química , Biomarcadores/análise , Biomarcadores/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Alcaloides Indólicos/análise , Isatis/metabolismo , Estrutura Molecular , Folhas de Planta/metabolismo
3.
J Exp Clin Cancer Res ; 38(1): 49, 2019 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-30717771

RESUMO

BACKGROUND: The JAK2-STAT signaling pathway plays a critical role in myeloproliferative neoplasms (MPN). An activating mutation in JAK2 (V617F) is present in ~ 95% of polycythemia vera, essential thrombocythemia, and primary myelofibrosis cases. This study aims to explore the selective JAK2V617F inhibitor, evaluate the efficacy and possible mechanism of ZT55 on MPN. METHODS: HTRF assays were conducted to evaluate the selective inhibition of ZT55 for JAKs. Cell apoptosis, proliferation, and cycle arrest assays were performed to examine the effect of ZT55 on HEL cell line with JAK2V617F mutation in vitro. Western analysis was used to monitor the expression and activity of proteins on JAK2/STAT pathway. A mice xenograft model was established to evaluate the antitumor efficacy of ZT55 in vivo. Peripheral blood samples from patients with the JAK2V617F mutation were collected to estimate the effect of ZT55 on erythroid colony formation by colony-forming assay. RESULTS: We found that ZT55 showed a selective inhibition of a 0.031 µM IC50 value against JAK2. It exhibited potent effects on the cellular JAK-STAT pathway, inhibiting tyrosine phosphorylation in JAK2V617F and downstream STAT3/5 transcription factors. ZT55 inhibited the proliferation of the JAK2V617F-expressing HEL cell line, leading to cell cycle arrest at the G2/M phase and induction of caspase-dependent apoptosis. Notably, ZT55 also significantly suppressed the growth of HEL xenograft tumors in vivo. Further evaluation indicated that ZT55 blocked erythroid colony formation of peripheral blood hematopoietic progenitors from patients carrying the JAK2V617F mutation. CONCLUSION: These results suggest that ZT55 is a highly-selective JAK2 inhibitor that can induce apoptosis of human erythroleukemia cells by inhibiting the JAK2-STAT signaling.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Janus Quinase 2/antagonistas & inibidores , Transtornos Mieloproliferativos/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Humanos , Isatis/química , Janus Quinase 2/sangue , Janus Quinase 2/genética , Masculino , Camundongos , Camundongos Nus , Transtornos Mieloproliferativos/sangue , Transtornos Mieloproliferativos/genética , Células-Tronco Neoplásicas/efeitos dos fármacos , Mutação Puntual , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacologia , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT5/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Chem Biodivers ; 16(3): e1800579, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30557446

RESUMO

Leaves of the plant species Isatis indigotica Fortune ex Lindl. (Chinese woad) produce the metabolites tryptanthrin, indirubin and N-formylanthranilic acid upon spraying with an aqueous solution of copper chloride but not after spraying with water. The antifungal activities of these metabolites against the phytopathogens Alternaria brassicicola, Leptosphaeria maculans and Sclerotinia sclerotiorum established that tryptanthrin is a much stronger growth inhibitor of L. maculans than the phytoalexin camalexin. The biosynthetic precursors of tryptanthrin and N-formylanthranilic acid are proposed based on the deuterium incorporations of isotopically labeled compounds. The overall results suggest that tryptanthrin is a phytoalexin and indirubin and N-formylanthranilic acid are phytoanticipins in the plant species I. indigotica and that chemical diversity and biodiversity are intimately connected.


Assuntos
Alternaria/efeitos dos fármacos , Antifúngicos/farmacologia , Ascomicetos/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Isatis/química , Quinazolinas/farmacologia , ortoaminobenzoatos/farmacologia , Antifúngicos/química , Antifúngicos/isolamento & purificação , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Indóis/química , Indóis/isolamento & purificação , Indóis/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Quinazolinas/química , Quinazolinas/isolamento & purificação , Relação Estrutura-Atividade , ortoaminobenzoatos/química , ortoaminobenzoatos/isolamento & purificação
5.
Fitoterapia ; 128: 169-174, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29787805

RESUMO

Seven new N-acylanthranilic acid derivatives (1-3, 4a/4b, 5a/5b) including two pairs of enantiomers (4a/4b and 5a/5b) were isolated from the leaves of Isatis indigotica Fortune. Their chemical structures were elucidated by extensive spectroscopic data analyses. The absolute configurations of compounds 4a/4b and 5a/5b were determined by comparison of the experimental and calculated ECD spectra. All compounds were tested for their anti-Aß1-42 aggregation activity. As a result, compounds 1 (72.1%), 2 (79.8%) and 5a (81.8%) showed stronger inhibitory activity than the positive control curcumin (67.0%). By the comparison between 5a (81.8%) and 5b (63.1%), it was found that stereochemical configurations may affect Aß1-42 aggregation activity, which was discussed through the molecular docking results of compounds 5a and 5b.


Assuntos
Peptídeos beta-Amiloides/antagonistas & inibidores , Isatis/química , Fragmentos de Peptídeos/antagonistas & inibidores , Folhas de Planta/química , ortoaminobenzoatos/isolamento & purificação , Simulação de Acoplamento Molecular , Estereoisomerismo
6.
Chem Biodivers ; 15(7): e1800152, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29696796

RESUMO

Four natural compounds were obtained by concentrating, separating and purifying from the Folium isatidis. These natural compounds have been characterized by elemental analysis, IR spectrum, NMR and single-crystal X-ray diffraction analysis. The results show that these natural compounds are 4(3H)-quinazolinone (I), 2,4(1H,3H)-quinazolinedione (II), methyl 3,4-dihydro-4-oxoquinazoline-2-carboxylate (III) and ethyl 3,4-dihydro-4-oxoquinazoline-2-carboxylate (IV). The antibacterial activity experiment showed that I and II had better activity against Staphylococcus aureus, Escherichia coli, Bacillus subtilis and Salmonella than III, IV and other multiple components, because III and IV have long branches and steric hindrance effect. Compounds I and II have planar structure, which can more easily combine with these bacteria and kill them. The above results have good guiding significance for studying the antibacterial activity for single components or mixtures from natural origin.


Assuntos
Antibacterianos/farmacologia , Produtos Biológicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Isatis/química , Antibacterianos/química , Antibacterianos/isolamento & purificação , Bacillus subtilis/efeitos dos fármacos , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Cristalografia por Raios X , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Folhas de Planta/química , Salmonella/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos
7.
Phytochemistry ; 149: 132-139, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29499466

RESUMO

Six undescribed alkaloids, indiforine A-F, together with four known ones, were isolated from the leaves of Isatis indigotica Fortune. Their structures were elucidated on the basis of extensive spectroscopic analyses. The absolute configurations of indiforine A and B were determined by comparison of the experimental and calculated electronic circular dichroism spectra, as well as experimental and calculated optical rotations. The isolated alkaloids were evaluated for their neuroprotective activities against H2O2-induced cell injury in human neuroblastoma SH-SY5Y cells. The results showed that in H2O2-induced SH-SY5Y cell injury models, indiforine A and B exhibited potent neuroprotective activities. Further investigation of the most potent indiforine A by Hoechst 33258 staining and Annexin V/PI analysis demonstrated that it could protect SH-SY5Y cells from oxidative damage through inhibiting cell apoptosis.


Assuntos
Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Alcaloides Indólicos/isolamento & purificação , Isatis/química , Fármacos Neuroprotetores/isolamento & purificação , Fármacos Neuroprotetores/farmacologia , Folhas de Planta/química , Apoptose/efeitos dos fármacos , China , Medicamentos de Ervas Chinesas/química , Humanos , Peróxido de Hidrogênio/farmacologia , Alcaloides Indólicos/química , Alcaloides Indólicos/farmacologia , Estrutura Molecular , Fármacos Neuroprotetores/química , Raízes de Plantas/química
8.
Phytochemistry ; 144: 127-140, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28930667

RESUMO

The brassicaceous herb, Isatis tinctoria, is an ancient medicinal plant whose rosette leaf extracts have anti-inflammatory and anti-allergic activity. Brassicaceae are known to accumulate a variety of phenylpropanoids in their rosette leaves acting as antioxidants and a UV-B shield, and these compounds often have pharmacological potential. Nevertheless, knowledge about the phenylpropanoid content of I. tinctoria leaves remains limited to the characterization of a number of flavonoids. In this research, we profiled the methanol extracts of I. tinctoria fresh leaf extracts by liquid chromatography - mass spectrometry (LC-MS) and focused on the phenylpropanoid derivatives. We report the structural characterization of 99 compounds including 18 flavonoids, 21 mono- or oligolignols, 2 benzenoids, and a wide spectrum of 58 hydroxycinnamic acid esters. Besides the sinapate esters of malate, glucose and gentiobiose, which are typical of brassicaceous plants, these conjugates comprised a large variety of glucaric acid esters that have not previously been reported in plants. Feeding with 13C6-glucaric acid showed that glucaric acid is an acyl acceptor of an as yet unknown acyltransferase activity in I. tinctoria rosette leaves. The large amount of hydroxycinnamic acid derivatives changes radically our view of the woad metabolite profile and potentially contributes to the pharmacological activity of I. tinctoria leaf extracts.


Assuntos
Ácido Glucárico/isolamento & purificação , Isatis/química , Folhas de Planta/química , Propanóis/isolamento & purificação , Ácido Glucárico/química , Ácido Glucárico/metabolismo , Isatis/metabolismo , Conformação Molecular , Folhas de Planta/metabolismo , Propanóis/química , Propanóis/metabolismo
9.
Chem Biodivers ; 14(8)2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28622440

RESUMO

The present work focused on the evaluation of the antioxidant and cytotoxic activities of the phenolic-rich fraction (ItJ-EAF) obtained from cauline leaves collected in January from Isatis tinctoria L. (Brassicaceae) growing wild around Acireale (Sicily, Italy). The total phenolic, flavonoid, and condensed tannin contents of the fraction were determined spectrophotometrically, whereas the phenolic profile was assessed by HPLC-PDA/ESI-MS analysis. A total of 20 compounds were positively identified and twelve out of them were never previously reported in I. tinctoria leaves. The fraction exhibited good radical scavenging activity in DPPH test (IC50  = 0.6657 ± 0.0024 mg/ml) and reducing power (3.87 ± 0.71 ASE/ml), whereas, it neither showed chelating activity nor was able to counteract H2 O2 induced oxidative stress damage in Escherichia coli. The antiproliferative effect was evaluated in vitro on two human anaplastic thyroid carcinoma cell lines (CAL-62 and 8505C) by MTT assay. At the highest tested concentration ItJ-EAF significantly reduced (80%) the growth of CAL-62 cells. No cytotoxicity against Artemia salina was observed. It can be concluded that I. tinctoria cauline leaves represent a source of phenolic compounds which could be potentially used as chemopreventive or adjuvant agents against cancer.


Assuntos
Isatis/química , Fenóis/química , Fenóis/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Humanos , Peróxido de Hidrogênio/toxicidade , Isatis/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fenóis/isolamento & purificação , Folhas de Planta/química , Folhas de Planta/metabolismo , Sicília , Espectrometria de Massas por Ionização por Electrospray
10.
J Asian Nat Prod Res ; 19(6): 529-540, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28475367

RESUMO

Six new indole alkaloid diglycosides named isatigotindolediosides A-F (1-6), along with three known analogs (7-9), were isolated from an aqueous extract of the Isatis indigotica roots (ban lan gen). Their structures including the absolute configurations were determined by comprehensive spectroscopic data analysis, combined with enzyme or acid hydrolysis, and comparison of experimental circular dichroism (CD) and calculated electronic circular dichroism (ECD) spectra. In the preliminary assays, compounds 3, 5, and 8 showed antiviral activity against Coxsackie virus B3.


Assuntos
Glicosídeos/isolamento & purificação , Alcaloides Indólicos/isolamento & purificação , Isatis/química , Raízes de Plantas/química , Antivirais/química , Antivirais/isolamento & purificação , Antivirais/farmacologia , Dicroísmo Circular , Enterovirus Humano B/efeitos dos fármacos , Glicosídeos/química , Glicosídeos/farmacologia , Alcaloides Indólicos/química , Alcaloides Indólicos/farmacologia , Estrutura Molecular , Água
11.
J Ind Microbiol Biotechnol ; 44(7): 997-1004, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28246965

RESUMO

The bacterial diversity in fermenting dye vats with woad (Isatis tinctoria L.) prepared and maintained in a functional state for approximately 12 months was examined using a combination of culture-dependent and -independent PCR-DGGE analyses and next-generation sequencing of 16S rRNA amplicons. An extremely complex ecosystem including taxa potentially contributing to both indigo reduction and formation, as well as indigo degradation was found. PCR-DGGE analyses revealed the presence of Paenibacillus lactis, Sporosarcina koreensis, Bacillus licheniformis, and Bacillus thermoamylovorans, while Bacillus thermolactis, Bacillus pumilus and Bacillus megaterium were also identified but with sequence identities lower than 97%. Dominant operational taxonomic units (OTUs) identified by pyrosequencing included Clostridium ultunense, Tissierella spp., Alcaligenes faecalis, Erysipelothrix spp., Enterococcus spp., Virgibacillus spp. and Virgibacillus panthothenicus, while sub-dominant OTUs included clostridia, alkaliphiles, halophiles, bacilli, moderately thermophilic bacteria, lactic acid bacteria, Enterobacteriaceae, aerobes, and even photosynthetic bacteria. Based on the current knowledge of indigo-reducing bacteria, it is considered that indigo-reducing bacteria constituted only a small fraction in the unique microcosm detected in the natural indigo dye vats.


Assuntos
Bacillus/isolamento & purificação , Fermentação , Isatis/microbiologia , Paenibacillus/isolamento & purificação , Sporosarcina/isolamento & purificação , Bacillus/classificação , Bacillus/metabolismo , Clostridium/isolamento & purificação , Clostridium/metabolismo , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Enterobacteriaceae/classificação , Enterobacteriaceae/isolamento & purificação , Enterobacteriaceae/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , Índigo Carmim/metabolismo , Isatis/química , Lactobacillales/classificação , Lactobacillales/isolamento & purificação , Lactobacillales/metabolismo , Paenibacillus/metabolismo , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/isolamento & purificação , Análise de Sequência de DNA , Sporosarcina/metabolismo
12.
BMC Complement Altern Med ; 16(1): 503, 2016 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-27919254

RESUMO

BACKGROUND: Qingdaisan (Formulated Indigo powder, QDS) are widely used for treatment of aphtha, sore throat and bleeding gums in China. The aim of the study is to evaluate the anti-inflammatory, antibacterial and dental ulcer therapeutic effects of QDS. METHODS: Dimethylbenzene-induced ear edema test and cotton pellet-induced granuloma test were used to evaluate anti-inflammatory activities of QDS on acute and chronic inflammatory. The healing time and local pathologic changes were used to assess the therapeutic effects of QDS on dental ulcer. The antibacterial activities of each component and the whole formulation of QDS were determined by agar well diffusion assay. High-dose and low-dose QDS were tested in this experiment and Gui Lin Watermelon Frost Powder (GLWFP) was used as positive control. RESULTS: Oral treatment with QDS significantly accelerated the healing of ulcerative lesions induced by phenol injury. The dental ulcers of high-dose QDS group were all healed within 6 days. It was shorter than those of low-dose QDS group and GLWFP group. Less quantity of inflammatory cells and plenty fibroblasts were observed in pathological section of QDS groups. QDS also exhibited significant anti-inflammatory activity both in acute and chronic animal models. Although some of the components exhibited antibacterial activities, the whole formulation of QDS didn't show any significant antibacterial activity in vitro. CONCLUSION: The study showed that QDS has obviously anti-inflammatory activity for both acute and chronic inflammatory, also has a remarkable effect for healing dental ulcer caused by phenol. QDS didn't have antibacterial activity to selected strains in vitro.


Assuntos
Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Animais , Medicamentos de Ervas Chinesas/uso terapêutico , Isatis/química , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Úlceras Orais/tratamento farmacológico , Úlceras Orais/patologia , Coelhos
13.
Planta Med ; 82(13): 1192-201, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27420350

RESUMO

Tryptanthrin and (E,Z)-3-(4-hydroxy-3,5-dimethoxybenzylidene)indolinone (indolinone) were recently isolated from Isatis tinctoria as potent anti-inflammatory and antiallergic alkaloids, and shown to inhibit COX-2, 5-LOX catalyzed leukotriene synthesis, and mast cell degranulation at low µM to nM concentrations. To assess their suitability for oral administration, we screened the compounds in an in vitro intestinal permeability assay using human colonic adenocarcinoma cells. For exact quantification of the compounds, validated UPLC-MS/MS methods were used. Tryptanthrin displayed high permeability (apparent permeability coefficient > 32.0 × 10(-6) cm/s) across the cell monolayer. The efflux ratio below 2 (< 1.12) and unchanged apparent permeability coefficient values in the presence of the P-glycoprotein inhibitor verapamil (50 µM) indicated that tryptanthrin was not involved in P-glycoprotein interactions. For indolinone, a low recovery was found in the human colon adenocarcinoma cell assay. High-resolution mass spectrometry pointed to extensive phase II metabolism of indolinone (sulfation and glucuronidation). Possible cardiotoxic liability of the compounds was assessed in vitro by measurement of an inhibitory effect on human ether-a-go-go-related gene tail currents in stably transfected HEK 293 cells using the patch clamp technique. Low human ether-a-go-go-related gene inhibition was found for tryptanthrin (IC50 > 10 µM) and indolinone (IC50 of 24.96 µM). The analysis of compounds using various in silico methods confirmed favorable pharmacokinetic properties, as well as a slight inhibition of the human ether-a-go-go-related gene potassium channel at micromolar concentrations.


Assuntos
Antialérgicos/farmacocinética , Anti-Inflamatórios não Esteroides/farmacocinética , Indóis/farmacocinética , Pirogalol/análogos & derivados , Quinazolinas/farmacocinética , Células CACO-2 , Permeabilidade da Membrana Celular , Cromatografia Líquida de Alta Pressão/métodos , Células HEK293 , Humanos , Absorção Intestinal , Isatis/química , Pirogalol/farmacocinética , Espectrometria de Massas em Tandem
14.
J Photochem Photobiol B ; 161: 17-24, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27203567

RESUMO

After malaria, Leishmaniasis is the most prevalent infectious disease in terms of fatality and geographical distribution. The availability of a limited number of antileishmanial agents, emerging resistance to the available drugs, and the high cost of treatment complicate the treatment of leishmaniasis. To overcome these issues, critical research for new therapeutic agents with enhanced antileishmanial potential and low treatment cost is needed. In this contribution, we developed a green protocol to prepare biogenic silver nanoparticles (AgNPs) and amphotericin B-bound biogenic silver nanoparticles (AmB-AgNPs). Phytochemicals from the aqueous extract of Isatis tinctoria were used as reducing and capping agents to prepare silver nanoparticles. Amphotericin B was successfully adsorbed on the surface of biogenic silver nanoparticles. The prepared nanoparticles were characterized by various analytical techniques. UV-Visible spectroscopy was employed to detect the characteristic localized surface plasmon resonance peaks (LSPR) for the prepared nanoparticles. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) studies revealed the formation of spherical silver nanoparticles with an average particle size of 10-20nm. The cubic crystalline structure of the prepared nanoparticles was confirmed by X-ray diffraction (XRD) study. FTIR spectroscopic analysis revealed that plant polyphenolic compounds are mainly involved in metal reduction and capping. Under visible light irradiation, biogenic silver nanoparticles exhibited significant activity against Leishmania tropica with an IC50 value of 4.2µg/mL. The leishmanicidal activity of these nanoparticles was considerably enhanced by conjugation with amphotericin B (IC50=2.43µg/mL). In conclusion, the findings of this study reveal that adsorption of amphotericin B, an antileishmanial drug, to biogenic silver nanoparticles, could be a safe, more effective and economic alternative to the available antileishmanial strategies.


Assuntos
Anfotericina B/química , Antiprotozoários/síntese química , Isatis/química , Nanopartículas Metálicas/química , Prata/química , Anfotericina B/farmacologia , Antiprotozoários/química , Antiprotozoários/farmacologia , Química Verde , Isatis/metabolismo , Leishmania tropica/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Tamanho da Partícula , Extratos Vegetais/química , Folhas de Planta/química , Folhas de Planta/metabolismo , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
15.
Planta Med ; 82(11-12): 1021-9, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27093249

RESUMO

The indolo[2,1-b]quinazoline alkaloid tryptanthrin was previously identified as a potent anti-inflammatory compound with a unique pharmacological profile. It is a potent inhibitor of cyclooxygenase-2, 5-lipooxygenase-catalyzed leukotriene synthesis, and nitric oxide production catalyzed by the inducible nitric oxide synthase. To characterize the pharmacokinetic properties of tryptanthrin, we performed a pilot in vivo study in male Sprague-Dawley rats (2 mg/kg bw i. v.). Moreover, the ability of tryptanthrin to cross the blood-brain barrier was evaluated in three in vitro human and animal blood-brain barrier models. Bioanalytical UPLC-MS/MS methods used were validated according to current international guidelines. A half-life of 40.63 ± 6.66 min and a clearance of 1.00 ± 0.36 L/h/kg were found in the in vivo pharmacokinetic study. In vitro data obtained with the two primary animal blood-brain barrier models showed a good correlation with an immortalized human monoculture blood-brain barrier model (hBMEC cell line), and were indicative of a high blood-brain barrier permeation potential of tryptanthrin. These findings were corroborated by the in silico prediction of blood-brain barrier penetration. P-glycoprotein interaction of tryptanthrin was assessed by calculation of the efflux ratio in bidirectional permeability assays. An efflux ratio below 2 indicated that tryptanthrin is not subjected to active efflux.


Assuntos
Barreira Hematoencefálica/metabolismo , Quinazolinas/farmacocinética , Animais , Linhagem Celular , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Isatis/química , Masculino , Estrutura Molecular , Extratos Vegetais/farmacocinética , Quinazolinas/síntese química , Quinazolinas/química , Ratos , Ratos Sprague-Dawley
16.
Int J Biol Macromol ; 87: 7-15, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26875535

RESUMO

Adjuvants can enhance vaccine immunogenicity and induce long-term enhancement of immune responses. Thus, adjuvants are important for vaccine research. Polysaccharides isolated from select Chinese herbs have been demonstrated to possess various beneficial functions and excellent adjuvant abilities. In the present study, the polysaccharides IIP-A-1 and IIP-2 were isolated from Isatis indigotica root and compared with the common vaccine adjuvant aluminum hydroxide via intramuscular co-administration of inactivated rabies virus rCVS-11-G into mice. Blood was collected to determine virus neutralizing antibody (VNA) titers and B and T lymphocyte activation status. Inguinal lymph node samples were collected and used to measure B lymphocyte proliferation. Splenocytes were isolated, from which antigen-specific cellular immune responses were detected via ELISpot, ELISA and intracellular cytokine staining. The results revealed that both types of polysaccharides induce more rapid changes and higher VNA titers than aluminum hydroxide. Flow cytometry assays revealed that the polysaccharides activated more B lymphocytes in the lymph nodes and more B and T lymphocytes in the blood than aluminum hydroxide. Antigen-specific cellular immune responses showed that IIP-2 strongly induced T lymphocyte proliferation in the spleen and high levels of cytokine secretion from splenocytes, whereas aluminum hydroxide induced proliferation in only a small number of lymphocytes and the secretion of only small quantities of cytokines. Collectively, these data suggest that the polysaccharide IIP-2 exhibits excellent adjuvant activity and can enhance both cellular and humoral immunity.


Assuntos
Adjuvantes Imunológicos/farmacologia , Isatis/química , Raízes de Plantas/química , Polissacarídeos/farmacologia , Vacinas Antirrábicas/imunologia , Animais , Anticorpos Neutralizantes/sangue , Antígenos Virais/imunologia , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Citocinas/metabolismo , Feminino , Imunidade Celular/efeitos dos fármacos , Imunidade Humoral/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Vírus da Raiva/efeitos dos fármacos , Vírus da Raiva/imunologia , Vírus da Raiva/patogenicidade , Baço/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Vacinas de Produtos Inativados/imunologia
17.
J Asian Nat Prod Res ; 18(1): 1-12, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26651370

RESUMO

Five new indole alkaloid glucosides named isatindigotindolosides A-E (1-5), along with three known analogs (6-8), were isolated from an aqueous extract of the Isatis indigotica roots. Their structures including the absolute configurations were determined based on comprehensive spectroscopic data analysis, combined with chemical methods and electronic circular dichroism spectra calculations. In the preliminary assays, compounds 1, 6 and 7 showed antiviral activity against influenza virus A/Hanfang/359/95 (H3N2) with IC50 values of 14.6-33.3 µM. Compound 1 also exhibited inhibitory effect against nitric oxide (NO) production in microglial cell BV2 with an inhibition ratio of 93.0% at 10 µM.


Assuntos
Antivirais/isolamento & purificação , Glucosídeos/isolamento & purificação , Alcaloides Indólicos/isolamento & purificação , Isatis/química , Animais , Antivirais/química , Antivirais/farmacologia , Glucosídeos/química , Glucosídeos/farmacologia , Alcaloides Indólicos/química , Alcaloides Indólicos/farmacologia , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Concentração Inibidora 50 , Camundongos , Microglia/citologia , Estrutura Molecular , Raízes de Plantas/química
18.
Biol Trace Elem Res ; 171(1): 224-34, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26432450

RESUMO

Epimedium polysaccharide (EPS) and isatis root polysaccharide (IRPS) were extracted, purified, and selenizingly modified by nitric acid-sodium selenite method to obtain nine selenizing EPSs (sEPSs), sEPS1-sEPS9 and nine selenizing IRPSs (sIRPSs), sIRPS1-sIRPS9, respectively. Their effects on chicken peripheral lymphocyte proliferation in vitro were compared by MTT assay. The results showed that selenium polysaccharides at appropriate concentration could promote lymphocyte proliferation more significantly than unmodified polysaccharides, sEPS5 and sIRPS5 with stronger actions were picked out and injected into the chickens vaccinated with Newcastle disease vaccine in vivo tests. The peripheral lymphocyte proliferation and serum antibody titer were determined. The results showed that sEPS5 and sIRPS5 could elevate serum antibody titer and promote lymphocyte proliferation more significantly than unmodified polysaccharides, sEPS5 possessed the strongest efficacy. These results indicate that selenylation modification can significantly enhance the immune-enhancing activity of EPS and IRPS, and sEPS5 can be as a new-type immunopotentiator of chickens.


Assuntos
Galinhas/imunologia , Epimedium/química , Isatis/química , Raízes de Plantas/química , Polissacarídeos/química , Polissacarídeos/imunologia , Selenito de Sódio/química , Animais , Proliferação de Células/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Masculino , Polissacarídeos/administração & dosagem , Polissacarídeos/isolamento & purificação , Selenito de Sódio/farmacologia
19.
Drug Des Devel Ther ; 9: 5601-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26491261

RESUMO

Sepsis, which is caused by severe infection, is an important cause of mortality, but effective clinical treatment against sepsis is extremely limited. As the main component of the outer membrane of Gram-negative bacteria, lipopolysaccharide (LPS) plays a major role in inflammatory responses. Studies have shown beneficial pharmacological effects for Folium isatidis. The present study further illuminated the effects of n-butanol extract from Folium isatidis in LPS-induced septic shock and identified the main active chemical components. Our study showed that pretreatment with n-butanol extract from Folium isatidis not only significantly inhibited LPS-induced tumor necrosis factor-α and interleukin-6 production but also markedly and dose dependently enhanced the recruitment of MyD88, the phosphorylation of extracellular signal-regulated kinase, and the degradation of IκB-α. Additionally, the extract exhibited dramatic protective effects against lung injury and death in mice with septic shock. Eight main active compounds were identified, including organic acids, glycoside, indolinones, and flavonoids. These findings provide a perspective on the respiratory protection offered by n-butanol extract from Folium isatidis in LPS-induced sepsis and outline a novel therapeutic strategy for the treatment of sepsis.


Assuntos
1-Butanol/química , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Mediadores da Inflamação/metabolismo , Isatis/química , Lipopolissacarídeos , Macrófagos Peritoneais/efeitos dos fármacos , Choque Séptico/prevenção & controle , Solventes/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Citocinas/imunologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas I-kappa B/metabolismo , Mediadores da Inflamação/imunologia , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/imunologia , Lesão Pulmonar/metabolismo , Lesão Pulmonar/prevenção & controle , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Fator 88 de Diferenciação Mieloide/metabolismo , Inibidor de NF-kappaB alfa , Fosforilação , Fitoterapia , Folhas de Planta , Plantas Medicinais , Proteólise , Choque Séptico/induzido quimicamente , Choque Séptico/imunologia , Choque Séptico/metabolismo , Transdução de Sinais/efeitos dos fármacos , Espectrometria de Massas em Tandem , Fatores de Tempo
20.
J Asian Nat Prod Res ; 17(7): 689-704, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26123248

RESUMO

Seven new glycosidic bisindole alkaloids, isatindigobisindolosides A-G (1-7), were isolated from an aqueous extract of the Isatis indigotica roots. Their structures including absolute configurations were determined by spectroscopic and chemical methods, together with calculations of electronic circular dichroism (ECD) spectra based on the quantum-mechanical time-dependent density functional theory. In the NMR spectra of 1-3, it is found that integration of H-2 and intensity of C-2 are affected not only by a substitution group at C-2 but also by solvents. Influences of the glucopyranosyloxy on the calculated ECD spectra of the glycosidic bisindole alkaloids are discussed. Compounds 2, 5, and 6 showed antiviral activity against both the influenza virus A/Hanfang/359/95 (H3N2) and Coxsackie virus B3 with IC50 values of 8.4-100.0 µM.


Assuntos
Antivirais/isolamento & purificação , Glicosídeos/isolamento & purificação , Alcaloides Indólicos/isolamento & purificação , Isatis/química , Antivirais/química , Antivirais/farmacologia , Glicosídeos/química , Glicosídeos/farmacologia , Alcaloides Indólicos/química , Alcaloides Indólicos/farmacologia , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Estrutura Molecular , Raízes de Plantas/química
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