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1.
Phys Rev Lett ; 122(20): 206402, 2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31172745

RESUMO

Two-dimensional (2D) quasiparticle standing waves originate from the interference of coherent quantum states and are usually created by the scattering off edges, atomic steps, or adatoms that induce large potential barriers. We report standing waves close to the valence band maximum (E_{V}), confined by electrically neutral domain walls of newly discovered ferroelectric SnTe monolayers, as revealed by spatially resolved scanning tunneling spectroscopy. Ab initio calculations show that this novel confinement arises from the polarization lifted hole valley degeneracy and a ∼90° rotation of the Brillouin zones that render holes' momentum mismatched across neighboring domains. These results show a potential for polarization-tuned valleytronics in 2D ferroelectrics.

2.
J Pharm Biomed Anal ; 174: 367-375, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31202879

RESUMO

Fufang Danshen Dripping Pill (FDDP) and Clopidogrel Bisulfate Tablet (CBT) are usually combined for treatment of coronary artery diseases in clinical. To investigate the pharmacokinetic interaction between FDDP and CBT after oral administration of FDDP, CBT and their combination in rats, a novel LC-MS method with segmented scan modes (multiple reaction monitoring and selected ion monitoring) and polarity (positive and negative ionization) was developed. Clopidogrel and the main active ingredients of FDDP, with different chemical and ionization properties, were simultaneously quantified in plasma in a single run. The method was validated in terms of specificity, linearity, precision, accuracy, recovery, matrix effect and stability. As a result, co-administration of FDDP and CBT significantly altered the pharmacokinetic parameters of danshensu, ginsenoside Rb1, dihydrotanshinone I, tanshinone I and tanshinone IIA of FDDP, as well as clopidogrel. Mechanism studies suggested that induction of liver cytochrome P450 isozymes CYP2C11 and CYP3A1 by co-administration, as well as inhibition of carboxyl esterase 1, was partly responsible for FDDP-CBT pharmacokinetic interactions. The developed LC-MS method could be used to simultaneously quantify different types of in vivo analytes in a single run, and the results could be used for clinical medication guidance of FDDP and CBT.

3.
Phytomedicine ; 58: 152866, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30831464

RESUMO

BACKGROUND: Herbal compatibility of compound formulas can enhance therapeutic effects or reduce side effects of the monarch drugs, but majority of compatibility mechanisms are still unknown. Sangju-Yin, a well-known Chinese compound formula, is currently used to treat common cold in clinical. PURPOSE: In this study, we proposed a strategy to explore the compatibility mechanism of Sangju-Yin by investigating P450 enzymes-based metabolic interactions between monarch drugs and the other constituent herbs. METHODS: Under the guidance of traditional Chinese medicine theory, the constituent herbs of Sangju-Yin were divided into four groups, including monarch drugs, monarch drugs with addition of minister drugs, monarch drugs with addition of minister and adjuvant drugs, as well as the whole recipe, namely monarch drugs with addition of minister, adjuvant and conductant drugs. Their effects on rats in vivo P450 (CYP1A2, CYP2A3, CYP2C6, CYP2C11 and CYP3A1) activities after oral administration were evaluated using probe drug assay based on LC-MS/MS. Moreover, effects of the four groups of herbs on mRNA expression of P450 enzymes after oral administration, as well as in vitro P450 activities after co-incubation, were investigated to explore the underlying mechanisms. RESULTS: Comparing with monarch drugs, addition of different constituent herbs significantly enhanced CYP1A2 and CYP2C6 activities, and inhibited CYP2A3 and CYP3A1 activities, indicating their possible influences on plasma concentrations of active constituents in the monarch drugs. Mechanism study suggested that these herbs affected P450 activities by transcriptional regulation and/or direct interaction with the enzymes. CONCLUSION: This study clarified the compatibility mechanism of Sangju-Yin from the aspect of P450 enzymes-based metabolic interactions, which would benefit better understanding of the therapeutic basis of Sangju-Yin.


Assuntos
Sistema Enzimático do Citocromo P-450/efeitos dos fármacos , Composição de Medicamentos , Interações de Medicamentos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicina Tradicional Chinesa , Animais , Cromatografia Líquida , Sistema Enzimático do Citocromo P-450/metabolismo , Medicamentos de Ervas Chinesas/química , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem
4.
J Ethnopharmacol ; 234: 189-196, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-30703494

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Clopidogrel is the recommended treatment by current clinical practice guidelines to prevent adverse cardiovascular events in patients with coronary heart disease (CHD), but this treatment regimen still fails and 5-40% patients display inadequate antiplatelet responses. Fufang Danshen Dripping Pill (FDDP), a Chinese patient drug, was used as the combination with clopidogrel to improve the therapeutic effect. However, the mechanism of the interaction between clopidogrel and FDDP has not been elucidated. MATERIALS AND METHODS: We have used non-targeted metabolism method based on GC-MS and LC-MS for the investigation of drug interactions between clopidogrel and FDDP. 63 patients were divided into four groups with different dosage regimen and the serum samples were collected for the analysis. RESULTS: We have found 5 and 55 differential metabolites between health volunteer group and CHD patients group, respectively. The contents of these differential metabolites had diverse changes in clopidogrel group, FDDP group, and drug combination group, indicating that the clopidogrel and FDDP combination can adjust the glycometabolism, lipid metabolism, and phospholipid metabolism, sequentially made the content of downstream related metabolites towards to the health volunteer group. CONCLUSION: This work has explained the mechanism of the interaction between clopidogrel and FDDP from the point of view of metabolic product change, and revealed the potential metabolic pathways it affects, which provided the new ideas for clinical medication.


Assuntos
Clopidogrel/administração & dosagem , Doença das Coronárias/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Cromatografia Líquida , Clopidogrel/farmacologia , Doença das Coronárias/metabolismo , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Interações Ervas-Drogas , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Espectrometria de Massas , Metabolômica/métodos , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/farmacologia , Adulto Jovem
5.
Artigo em Inglês | MEDLINE | ID: mdl-30690396

RESUMO

Ginkgo biloba leaves extract (GBE), one of the most widely used traditional Chinese medicines worldwide, can be used for the treatment of diabetes mellitus (DM). However, its biotransformation in liver is not fully known under the state of DM. In this study, an off-line hydrophilic interaction × reversed-phase two-dimensional liquid chromatography (HILIC × RP 2D-LC) system coupled with diode array detection (DAD) and quadrupole time-of-flight mass spectrometry (q/TOF-MS) was established for the qualification and quantification of the biotransformation of GBE in normal and diabetic rat liver microsomes (RLMs). 6 metabolites were tentatively identified according to the exact molecular weights and the characteristic fragment ions provided by q/TOF-MS data. The results of metabolic stability showed that the metabolic ratio of four target compounds including quercetin, genistein, kaempferol and isorhamnetin in diabetic RLMs were significantly enhanced when comparing with normal RLMs. The results of enzyme kinetics showed that compared with normal RLMs, the Michaelis-Menten constant (Km) value of genistein was obvious increased while its maximal velocity (Vmax) and intrinsic clearance (CLint) values were significantly decreased by diabetic RLMs, and the Vmax and CLint values of kaempferol and isorhamnetin were notably enhanced while their Km values were markedly reduced. For the half-time (t1/2) values of four target compounds and the Km, Vmax and CLint values of quercetin, there were not statistically significant changes between normal and diabetic RLMs. The results suggest that the developed off-line 2D LC-DAD-q/TOF-MS method is an easy and accurate approach for the study of GBE biotransformation in RLMs and may provide the essential data for further pharmacological and clinical studies of GBE.


Assuntos
Cromatografia de Fase Reversa/métodos , Espectrometria de Massas/métodos , Microssomos Hepáticos/metabolismo , Extratos Vegetais/análise , Extratos Vegetais/farmacocinética , Animais , Biotransformação , Limite de Detecção , Modelos Lineares , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes
6.
J Pharm Biomed Anal ; 166: 30-39, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30599279

RESUMO

Diabetic nephropathy (DN) is one of the leading causes of death in diabetes mellitus (DM). Early warning and therapy has significant clinical value for DN. This research sought to find biomarkers to predict the occurrence and development of DN and the intervention of Ginkgo biloba leaves extract (GBE) by quantifying fatty acids, amino acids, and nucleosides and nucleobases in rat plasma. Samples were respectively collected at the weekend of 5-10 weeks after diabetic rats induced by streptozotocin were defined. Plasma fasting blood-glucose, kidney index, blood urea nitrogen, creatinine, urine albumin excretion and ultrastructural morphology of kidney were measured or observed. Fatty acids, amino acids and nucleosides and nucleobases in rat plasma were analyzed by gas chromatography or liquid phase chromatography and mass spectrometry, respectively. From the biochemical index and morphological change of kidney, the rats from the 5th to 7th week were in the stage of DM while from the begin of 8th week the rats were suggested in the early stage of DN. The results of quantitative metabolomics showed that 16 differential metabolites were related to the progression of DN, and oleic acid, glutamate and guanosine might be the potential biomarkers of kidney injury. 14 differential metabolites were related to GBE against the progression of DN, while oleic acid and glutamate might be the potential biomarkers of GBE against kidney injury. Those findings potentially promote the understanding of the pathogenic progression of DN and reveal the therapeutic mechanism of GBE against DN.


Assuntos
Aminoácidos/sangue , Nefropatias Diabéticas/sangue , Ácidos Graxos/sangue , Metabolômica , Nucleosídeos/sangue , Extratos Vegetais/uso terapêutico , Albuminúria , Animais , Biomarcadores/sangue , Glicemia/metabolismo , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/tratamento farmacológico , Rim/patologia , Rim/ultraestrutura , Masculino , Ratos
7.
Biosci Biotechnol Biochem ; 83(4): 666-674, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30585123

RESUMO

Asparagus (Asparagus officinalis) has several traits that make it a useful model for cytogenetic studies, however, few studies of the meiosis process have been made in asparagus. Here, we present in detail an atlas of male meiosis in asparagus, from preleptotene to telophase II. The meiosis process in asparagus is largely similar to those of the well-characterized model plants Arabidopsis thaliana, Zea mays, and Oryza sativa. However, most asparagus prophase I meiotic chromosomes show a strongly aggregated morphology, and this phenotype persists through the pachytene stage, highlighting a property in the control of chromosome migration and distribution in asparagus. Further, we observed no obvious banding of autofluorescent dots between divided nuclei of asparagus meiocytes, as one would expect in Arabidopsis. This description of wild-type asparagus meiosis will serve as a reference for the analyses of meiotic mutants, as well as for comparative studies among difference species. Abbreviations: DAPI: 4',6-diamidino-2-phenylindole; FISH: fluorescence in situ hybridization; PBS: phosphate-buffered saline; PMC: pollen mother cell; SEM: Scanning Electron Microscope.


Assuntos
Asparagus (Planta)/ultraestrutura , Cromossomos de Plantas/ultraestrutura , Meiose , Células Vegetais/ultraestrutura , Pólen/ultraestrutura , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/ultraestrutura , Asparagus (Planta)/genética , Asparagus (Planta)/crescimento & desenvolvimento , Núcleo Celular/metabolismo , Núcleo Celular/ultraestrutura , Cromossomos de Plantas/química , Flores/genética , Flores/crescimento & desenvolvimento , Flores/ultraestrutura , Hibridização in Situ Fluorescente , Microscopia Eletrônica de Varredura , Células Vegetais/metabolismo , Pólen/genética , Pólen/crescimento & desenvolvimento
8.
Front Pharmacol ; 9: 1167, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30386241

RESUMO

Sangju Ganmao tablet (SGT), a well-known Chinese patent medicine used to treat cold symptoms, is made from eight herbal medicines. In this study, an off-line hydrophilic interaction × reversed-phase two-dimensional liquid chromatography (HILIC × RP 2D-LC) method was developed to comprehensively separate the chemical constituents of SGT. Through optimization of the experimental conditions, a total of 465 peaks were finally detected in SGT, and the structures of 54 selected compounds were fully identified or tentatively characterized by quadrupole time-of-flight mass spectrometry (qTOF-MS) analysis. The established 2D-LC analysis showed high orthogonality (63.62%) and approximate 11-fold improvement in peak capacity (2399 and 1099, obtained by two calculation methods), in contrast to conventional one-dimensional RPLC separation. The eight component herbs of SGT were also respectively separated by using the 2D-LC system, and we found that a total of 12 peaks detected in SGT were not discovered in any component herbs. These newly generated chemical constituents would benefit better understanding of the compatibility mechanism of the component herbs. The strategy established in this study could be used for systematic chemical comparison of SGT and its component herbs, which contributes to exploration of herbal compatibility mechanism.

9.
Adv Mater ; : e1804428, 2018 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-30387192

RESUMO

2D SnTe films with a thickness of as little as 2 atomic layers (ALs) have recently been shown to be ferroelectric with in-plane polarization. Remarkably, they exhibit transition temperatures (Tc ) much higher than that of bulk SnTe. Here, combining molecular beam epitaxy, variable temperature scanning tunneling microscopy, and ab initio calculations, the underlying mechanism of the Tc enhancement is unveiled, which relies on the formation of γ-SnTe, a van der Waals orthorhombic phase with antipolar inter-layer coupling in few-AL thick SnTe films. In this phase, 4n - 2 AL (n = 1, 2, 3…) thick films are found to possess finite in-plane polarization (space group Pmn21 ), while 4n AL thick films have zero total polarization (space group Pnma). Above 8 AL, the γ-SnTe phase becomes metastable, and can convert irreversibly to the bulk rock salt phase as the temperature is increased. This finding unambiguously bridges experiments on ultrathin SnTe films with predictions of robust ferroelectricity in GeS-type monochalcogenide monolayers. The observed high transition temperature, together with the strong spin-orbit coupling and van der Waals structure, underlines the potential of atomically thin γ-SnTe films for the development of novel spontaneous polarization-based devices.

10.
J Pharm Biomed Anal ; 160: 301-313, 2018 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-30114608

RESUMO

Herbal medicines are complicated chemical systems containing hundreds of small molecules of various polarities, structural types, and contents. Thus far, the chromatographic separation of herbal extracts is still a big challenge. Two-dimensional liquid chromatography (2DLC) has become an attractive separation tool in the past few years. Particularly, a lot of attention has been paid to on-line 2DLC. In this review, we aim to give an overview on applications of on-line 2DLC in the chemical analysis of herbal medicines since 2010. Firstly, classification and general configurations of on-line 2DLC were briefly introduced. Then, we summarized main applications in herbal medicines of heart-cutting 2DLC (LC-LC), comprehensive 2DLC (LC × LC), and their combinations, with emphasis on LC × LC. Mass spectrometry is the most popular detector coupled with 2DLC, which allows sensitive and accurate structural characterization of herbal compounds. Finally, future developments in on-line 2DLC techniques were also discussed.

12.
World J Gastroenterol ; 23(39): 7168-7173, 2017 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-29093625

RESUMO

AIM: To investigate the expression of annexin A5 in serum and tumor tissue of patients with colon cancer and to analyze its clinical significance. METHODS: Ninety-three patients with colon cancer treated at our hospital between February 2013 and March 2016 were included in an observation group, and 40 healthy individuals were included in a control group. Enzyme-linked immunosorbent assay was performed to determine the serum level of annexin A5, while immunohistochemistry was performed to determine the expression of annexin A5 in cancer tissues. RESULTS: The serum level of annexin A5 was 0.184 ± 0.043 ng/mL in the observation group, which was significantly higher than that in the control group (P < 0.05). Annexin A5 expression was detected in 79.31% of the patients with lymph node metastasis, which was significantly higher than that in patients without lymph node metastasis (P < 0.05). Moreover, annexin A5 expression was detected in 86.96% of the patients with stage III to IV disease, which was significantly higher than that in patients with stage I to II disease (P < 0.05). The serum level of annexin A5 was 0.215 ± 0.044 ng/mL in patients whose tumors were positive for annexin A5 expression, which was significantly higher than that in patients whose tumors were negative for annexin A5 expression (P < 0.05). The serum level of annexin A5 was correlated with annexin A5 expression in colon cancer tissues (r = 0.312, P < 0.05). When a cutoff value of > 0.148 ng/mL for serum level of annexin A5 was used in the diagnosis of colon cancer, the sensitivity was 83.90%, and the specificity was 57.50%. CONCLUSION: For patients with colon cancer, annexin A5 expression in cancer tissues is related to lymph node metastasis and tumor grade. Serum level of annexin A5 is related to annexin A5 expression in cancer tissues and is of diagnostic relevance.


Assuntos
Anexina A5/sangue , Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/química , Área Sob a Curva , Estudos de Casos e Controles , Neoplasias Colorretais/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Curva ROC , Reprodutibilidade dos Testes
13.
Phytomedicine ; 34: 59-66, 2017 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-28899510

RESUMO

BACKGROUND: Licorice and its constituents, especially licorice flavonoids have been reported to possess significant hepatoprotective activities. However, previous studies mainly focus on the extract and major compounds, and few reports are available on other licorice compounds. PURPOSE: This work aims to evaluate the in vitro hepatoprotective activities of licorice compounds and screen active compounds, and to establish the structure-activity relationship. METHODS: A compound library consisting of 180 compounds from three medicinal licorice species, Glycyrrhiza uralensis, G. glabra and G. inflata was established. HepG2 cells were incubated with the compounds, together with the treatment of 0.35% CCl4 for 6 h and 14 mM APAP for 24 h, respectively. RESULTS: A total of 62 compounds at 10 µM showed protective effects against CCl4 to improve cell viability from 52.5% to >60%, and compounds 5 (licoflavone A), 104 (3,4-didehydroglabridin), 107 (isoliquiritigenin), 108 (3,4,3',4'-tetrahydroxychalcone), and 111 (licochalcone B) showed the most potent activities, improving cell viability to >80%. And 64 compounds showed protective effects against APAP to improve cell viability from 52.0% to >60%, and compounds 47 (derrone), 76 (xambioona), 77 ((2S)-abyssinone I), 107 (isoliquiritigenin), 118 (licoagrochalcone A), and 144 (2'-O-demethybidwillol B) showed the most potent activities, improving cell viability to >80%. Preliminary structure-activity analysis indicated that free phenolics compounds especially chalcones showed relatively stronger protective activities than other types of compounds. CONCLUSION: Compounds 5, 76, 104, 107, 111, 118 and 144 possess potent activities against both CCl4 and APAP, and 5, 76 and 118 were reported for the first time. They could be the major active compounds of licorice for the treatment of liver injury.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Glycyrrhiza/química , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Acetaminofen/toxicidade , Tetracloreto de Carbono/toxicidade , Chalconas , Flavonoides , Células Hep G2 , Humanos , Fígado/efeitos dos fármacos , Estrutura Molecular , Relação Estrutura-Atividade
14.
Bioorg Med Chem ; 25(20): 5522-5530, 2017 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-28835349

RESUMO

Glycyrrhiza inflata (licorice) has been used to treat liver diseases for a long history. However, the bioactive compounds are still not clear. In this work, 77 compounds, including 9 new ones, were isolated from the EtOAc extract of the roots and rhizomes of G. inflata. The Nrf2 activation activities of all compounds were screened using ARE-luciferase reporter assay on HepG2C8 cells. The results indicated a number of chalcones were potent Nrf2 activators, including 11 (licochalcone A, 4.07-fold), 12 (licochalcone B, 5.17-fold), and 19 (echinatin, 4.09-fold). Further studies indicated that 11, 12 and 19 remarkably attenuated CCl4-induced acute liver injury in mice (10 or 50mg/kg, 7days, ig.). These compounds could be promising hepatoprotective natural agents.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Glycyrrhiza/química , Fator 2 Relacionado a NF-E2/metabolismo , Extratos Vegetais/farmacologia , Administração Oral , Animais , Tetracloreto de Carbono , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Células Hep G2 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Estrutura Molecular , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química , Ratos , Ratos Sprague-Dawley
15.
J Pharm Biomed Anal ; 146: 68-78, 2017 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-28854404

RESUMO

Ginkgo biloba extract (GBE), derived from the leaves of Ginkgo biloba L., is one of the most widely used traditional Chinese medicines worldwide. Due to high structural diversity and low abundance of chemical constituents in GBE, conventional reversed-phase liquid chromatography has limited power to meet the needs of its quality control. In this study, an off-line hydrophilic interaction×reversed-phase two-dimensional liquid chromatography (HILIC×RP 2D-LC) system coupled with diode array detection (DAD) and quadrupole time-of-flight mass spectrometry (qTOF-MS) was established to comprehensively analyze the chemical constituents of GBE. After optimizing the chromatographic columns and mobile phase of 2D-LC, a Waters XBridge Amide column using acetonitrile/water/formic acid as the mobile phase was selected as the first dimension to fractionate GBE, and the obtained fractions were further separated on an Agilent Zorbax XDB-C18 column with methanol/water/formic acid as the mobile phase. As a result, a total of 125 compounds were detected in GBE. The orthogonality of the 2D-LC system was 69.5%, and the practical peak capacity was 3864 and 2994, respectively, calculated by two different methods. The structures of 104 compounds were tentatively characterized by qTOF-MS analysis, and 21 of them were further confirmed by comparing with reference standards. This established HILIC×RP 2D-LC-qTOF/MS system can greatly improve the separation and characterization of natural products in GBE or other complicated herbal extracts.


Assuntos
Medicamentos de Ervas Chinesas/química , Ginkgo biloba/química , Extratos Vegetais/química , Acetonitrilos/química , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia de Fase Reversa/métodos , Flavonoides/química , Formiatos/química , Interações Hidrofóbicas e Hidrofílicas , Medicina Tradicional Chinesa/métodos , Folhas de Planta/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Água/química
16.
Toxicol Appl Pharmacol ; 326: 25-33, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28416456

RESUMO

Licorice (Glycyrrhiza uralensis Fisch.) possesses significant anti-cancer activities, but the active ingredients and underlying mechanisms have not been revealed. By screening the cytotoxic activities of 122 licorice compounds against SW480 human colorectal adenocarcinoma cells, we found that licoricidin (LCD) inhibited SW480 cell viability with an IC50 value of 7.2µM. Further studies indicated that LCD significantly induced G1/S cell cycle arrest and apoptosis in SW480 cells, accompanied by inhibition of cyclins/CDK1 expression and activation of caspase-dependent pro-apoptotic signaling. Meanwhile, LCD promoted autophagy in SW480 cells, and activated AMPK signaling and inhibited Akt/mTOR pathway. Overexpression of a dominant-negative AMPKα2 abolished LCD-induced inhibition of Akt/mTOR, autophagic and pro-apoptotic signaling pathways, and significantly reversed loss of cell viability, suggesting activation of AMPK is essential for the anti-cancer activity of LCD. In vivo anti-tumor experiments indicated that LCD (20mg/kg, i.p.) significantly inhibited the growth of SW480 xenografts in nude mice with an inhibitory rate of 43.5%. In addition, we obtained the glycosylated product LCDG by microbial transformation, and found that glycosylation slightly enhanced the in vivo anti-cancer activities of LCD. This study indicates that LCD could inhibit SW480 cells by inducing cycle arrest, apoptosis and autophagy, and is a potential chemopreventive or chemotherapeutic agent against colorectal cancer.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Benzopiranos/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Relação Dose-Resposta a Droga , Glicosilação , Humanos , Concentração Inibidora 50 , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Fatores de Tempo , Transfecção , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
17.
J Nat Prod ; 80(2): 334-346, 2017 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-28140583

RESUMO

In an attempt to discover bioactive agents from the herbal medicine Glycyrrhiza glabra (widely known as licorice), 11 new phenolic compounds, glycybridins A-K (1-11), along with 47 known phenolics (12-58) were isolated. Their structures were elucidated on the basis of extensive NMR and MS analyses as well as experimental and computed ECD data. According to the clinical therapeutic effects of licorice, enzyme or cell-based bioactivity screenings of 1-58 were conducted. A number of compounds significantly activate Nrf2, inhibit tyrosinase or PTP1B, inhibit LPS-induced NO production and NF-κB transcription, and inhibit the proliferation of human cancer cells (HepG2, SW480, A549, MCF7). Glycybridin D (4) showed moderate cytotoxic activities against the four cancer cell lines, with IC50 values ranging from 4.6 to 6.6 µM. Further studies indicated that 4 (10 mg/kg, ip) decreased tumor mass by 39.7% on an A549 human lung carcinoma xenograft mice model, but showed little toxicity.


Assuntos
Glycyrrhiza/química , Fenóis/isolamento & purificação , Fenóis/farmacologia , Plantas Medicinais/química , Animais , Antioxidantes/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos , Estrutura Molecular , Monofenol Mono-Oxigenase/antagonistas & inibidores , NF-kappa B/antagonistas & inibidores , Óxido Nítrico/biossíntese , Fenóis/química , Raízes de Plantas/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Rizoma/química
18.
Anal Chem ; 89(5): 3146-3153, 2017 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-28192986

RESUMO

Secondary metabolites are usually the bioactive components of medicinal plants. The difference in the secondary metabolisms of closely related plant species and their hybrids has rarely been addressed. In this study, we conducted a holistic secondary metabolomics analysis of three medicinal Glycyrrhiza species (G. uralensis, G. glabra, and G. inflata), which are used as the popular herbal medicine licorice. The Glycyrrhiza species (genotype) for 95 batches of samples were identified by DNA barcodes of the internal transcribed spacer and trnV-ndhC regions, and the chemotypes were revealed by LC/UV- or LC/MS/MS-based quantitative analysis of 151 bioactive secondary metabolites, including 17 flavonoid glycosides, 24 saponins, and 110 free phenolic compounds. These compounds represented key products in the biosynthetic pathways of licorice. For the 76 homozygous samples, the three Glycyrrhiza species showed significant biosynthetic preferences, especially in coumarins, chalcones, isoflavanes, and flavonols. In total, 27 species-specific chemical markers were discovered. The 19 hybrid samples indicated that hybridization could remarkably alter the chemical composition and that the male parent contributed more to the offspring than the female parent did. This is hitherto the largest-scale targeted secondary metabolomics study of medicinal plants and the first report on uniparental inheritance in plant secondary metabolism. The results are valuable for biosynthesis, inheritance, and quality control studies of licorice and other medicinal plants.

19.
Science ; 353(6296): 274-8, 2016 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-27418506

RESUMO

Stable ferroelectricity with high transition temperature in nanostructures is needed for miniaturizing ferroelectric devices. Here, we report the discovery of the stable in-plane spontaneous polarization in atomic-thick tin telluride (SnTe), down to a 1-unit cell (UC) limit. The ferroelectric transition temperature T(c) of 1-UC SnTe film is greatly enhanced from the bulk value of 98 kelvin and reaches as high as 270 kelvin. Moreover, 2- to 4-UC SnTe films show robust ferroelectricity at room temperature. The interplay between semiconducting properties and ferroelectricity in this two-dimensional material may enable a wide range of applications in nonvolatile high-density memories, nanosensors, and electronics.

20.
J Chromatogr A ; 1454: 15-25, 2016 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-27262372

RESUMO

The quality evaluation of patent drugs derived from traditional Chinese medicine (TCM) compound formulas has been challenging due to their complex chemical composition. In this study, we developed a solution to evaluate the quality of Gegen-Qinlian Decoction (GQD), an ancient four-herb TCM formula for the treatment of diarrhea and diabetes, together with its derived patent drugs by simultaneously quantifying 50 bioactive compounds. The samples were extracted by 100% methanol (for hydrophobic compounds) and 50% methanol in water (for hydrophilic compounds), respectively, and were separated on a Waters Acquity charged surface hybrid C18 column (2.1×100mm, 1.7µm) eluted with gradients of acetonitrile and water containing 0.1% formic acid at a flow rate of 400µL/min. The analytes were determined by ultra-high performance liquid chromatography coupled with tandem mass spectrometry in the selected reaction monitoring mode. The 50 compounds (including acidic and alkaline, hydrophilic and hydrophobic) were well resolved within 14min, and were determined using an internal standard method. The method was fully validated for precision, repeatability, and recovery. The limits of detection were 0.3-10.0ng/mL. Finally, this method was used to analyze 24 batches of GQD samples, including water decoction, pills, tablets, and oral solutions. Principal component analysis indicated significantly varied chemical compositions among these formulations. The tablets and pills contained higher concentrations of Scutellaria and Coptis compounds than the oral solutions, and the water decoction contained abundant glycosides and saponins. Moreover, the contents of flavanones and flavone O-glucuronides varied remarkably. This study provides a feasible solution for the comprehensive quality control of TCM patent drugs.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/química , Espectrometria de Massas em Tandem/métodos , Flavanonas , Glicosídeos , Limite de Detecção , Saponinas
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