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1.
Rapid Commun Mass Spectrom ; 38(14): e9766, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-38747108

RESUMEN

RATIONALE: Huahong tablet, a commonly used clinical Chinese patent medicine, shows good efficacy in treating pelvic inflammation and other gynaecological infectious diseases. However, the specific composition of Huahong tablets, which are complex herbal formulations, remains unclear. Therefore, this study aims to identify the active compounds and targets of Huahong tablets and investigate their mechanism of action in pelvic inflammatory diseases. METHODS: We utilised ultrahigh-performance liquid chromatography Q-Exactive-Orbitrap mass spectrometry and the relevant literature to identify the chemical components of Huahong tablets. The GNPS database was employed to further analyse and speculate on the components. Potential molecular targets of the active ingredients were predicted using the SwissTargetPrediction website. Protein-protein interaction analysis was conducted using the STRING database, with visualisation in Cytoscape 3.9.1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the DAVID database. Additionally, a traditional Chinese medicine-ingredient-target-pathway network was constructed using Cytoscape 3.10.1. Molecular docking validation was carried out to investigate the interaction between core target and specific active ingredient. RESULTS: A total of 66 chemical components were identified, and 41 compounds were selected as potential active components based on the literature and the TCMSP database. Moreover, 38 core targets were identified as key targets in the treatment of pelvic inflammatory diseases with Huahong tablets. GO and KEGG enrichment analysis revealed 986 different biological functions and 167 signalling pathways. CONCLUSION: The active ingredients in Huahong tablets exert therapeutic effects on pelvic inflammatory diseases by acting on multiple targets and utilising different pathways. Molecular docking confirmed the high affinity between the specific active ingredients and disease targets.


Asunto(s)
Medicamentos Herbarios Chinos , Farmacología en Red , Enfermedad Inflamatoria Pélvica , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Cromatografía Líquida de Alta Presión/métodos , Enfermedad Inflamatoria Pélvica/tratamiento farmacológico , Humanos , Espectrometría de Masas/métodos , Femenino , Mapas de Interacción de Proteínas/efectos de los fármacos , Comprimidos/química , Simulación del Acoplamiento Molecular
2.
BMC Biol ; 21(1): 237, 2023 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-37904147

RESUMEN

BACKGROUND: Melanin plays important roles in morphological development, survival, host-pathogen interactions and in the virulence of phytopathogenic fungi. In Verticillum dahliae, increases in melanin are recognized as markers of maturation of microsclerotia which ensures the long-term survival and stress tolerance, while decreases in melanin are correlated with increased hyphal growth in the host. The conserved upstream components of the VdCmr1-regulated pathway controlling melanin production in V. dahliae have been extensively identified, but the direct activators of this pathway are still unclear. RESULTS: We identified two genes encoding conserved C2H2-type zinc finger proteins VdZFP1 and VdZFP2 adjacent to VdPKS9, a gene encoding a negative regulator of both melanin biosynthesis and microsclerotia formation in V. dahliae. Both VdZFP1 and VdZFP2 were induced during microsclerotia development and were involved in melanin deposition. Their localization changed from cytoplasmic to nuclear in response to osmotic pressure. VdZFP1 and VdZFP2 act as modulators of microsclerotia melanization in V. dahliae, as confirmed by melanin biosynthesis inhibition and supplementation with the melanin pathway intermediate scytalone in albino strains. The results indicate that VdZFP1 and VdZFP2 participate in melanin biosynthesis by positively regulating VdCmr1. Based on the results obtained with yeast one- and two-hybrid (Y1H and Y2H) and bimolecular fluorescence complementation (BiFC) systems, we determined the melanin biosynthesis relies on the direct interactions among VdZFP1, VdZFP2 and VdCmr1, and these interactions occur on the cell walls of microsclerotia. Additionally, VdZFP1 and/or VdZFP2 mutants displayed increased sensitivity to stress factors rather than alterations in pathogenicity, reflecting the importance of melanin in stress tolerance of V. dahliae. CONCLUSIONS: Our results revealed that VdZFP1 and VdZFP2 positively regulate VdCmr1 to promote melanin deposition during microsclerotia development, providing novel insight into the regulation of melanin biosynthesis in V. dahliae.


Asunto(s)
Ascomicetos , Verticillium , Melaninas , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Verticillium/genética , Dedos de Zinc , Enfermedades de las Plantas/microbiología
3.
Phys Chem Chem Phys ; 25(36): 24214-24233, 2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37691583

RESUMEN

Stable and efficient phosphors are highly important for light-emitting diodes (LEDs) with respect to their application in solid-state lighting, instead of conventional lamps for general lighting. However, some problems, like low stability, low photoluminescence (PL) efficiency, and serious thermal degradation, are commonly encountered in phosphors, limiting their applications in LEDs. Surface modifications for some phosphors commonly used in LED lighting, including fluoride, sulphide, silicate, oxide, nitride, and oxynitride phosphors, are presented in this review. By forming a protective surface layer, the stabilities against moisture and high temperature of fluoride- and sulphide-based phosphors were strengthened; by coating inorganic and organic materials around the particle surface, the PL efficiencies of silicate- and oxide-based phosphors were improved; by passivation treatment upon the phosphor surface, the thermal degradation of nitride- and oxynitride-based phosphors was reduced. Various technologies for surface modification are described in detail; moreover, the mechanisms of stability strengthening, PL efficiency improvement, and thermal degradation reduction are explained. In addition, embedding of phosphors in inorganic glass matrix, especially for quantum dots, is also introduced as an effective method to improve phosphor stability for LED applications. Finally, future developments of surface modification of phosphors are proposed.

4.
J Sep Sci ; 45(18): 3382-3392, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35851721

RESUMEN

Epimedium has a wide range of clinical applications; however, there have been numerous reports of adverse reactions in recent years, which has resulted in it being changed from a widely recognized "nontoxic" to a "potentially toxic" traditional Chinese medicine. The combination of Epimedium and Ligustri lucidi fructus is commonly used in the clinic. The purpose of this study was to investigate the pharmacokinetic characteristics of Epimedium and Ligustri lucidi fructus to explore the possible synergism and reduction in toxicity. Based on liquid chromatography tandem mass spectrometry, a method was established for the determination of icariin, epimedin A, epimedin B, epimedin C, baohuoside Ⅰ, and specnuezhenide in biological samples and was successfully applied to study the pharmacokinetics of the drug pair. The results showed that the five flavonoids (specnuezhenide could not be detected) could be rapidly absorbed into the blood, and the second peak time in vivo was earlier after the combination, indicating that the metabolic pathway may be changed. In addition, combination with Ligustri lucidi fructus could significantly reduce the concentration of 5 flavonoids in vivo and increase their elimination rate, which may attenuate their virulence, thus providing a reference for the rational clinical use of Epimedium.


Asunto(s)
Medicamentos Herbarios Chinos , Epimedium , Ligustrum , Cromatografía Líquida de Alta Presión , Flavonoides , Ligustrum/química , Medicina Tradicional China
5.
Biomed Chromatogr ; 36(1): e5251, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34606105

RESUMEN

Osmundacetone is a potential medicinal substance existing in ferns and has excellent antioxidant effects. This research aims to obtain the pharmacokinetic data for and metabolite products of osmundacetone. An UPLC-MS/MS quantitative method was established for the measurement of osmundacetonein in rat plasma over a linear range of 6.72-860.00 ng/ml. The signal to noise ratio of the lower limit of quantification was 60:1, the precision was <9.74% and the method had good selectivity and stability. The established method was successfully applied to the pharmacokinetic study of osmundacetone for the first time. Osmundacetone reached a peak at 0.25 h with a maximum value of 3283.33 µg/L. The apparent volume of distribution not multiplied by the bioavailability was 127.96 L/kg, and the half-life of osmundacetone was 5.20 h. At the same time, an UPLC-QE-Orbitrap-HRMS method was established to identify metabolites in plasma, urine and feces for the first time. A total of 30 metabolites were identified and the metabolic profile of osmundacetone was defined. In general, we have established a mass spectrometry quantitative method for osmundacetone for the first time and characterized its metabolic characteristics in rats.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Cetonas , Espectrometría de Masas en Tándem/métodos , Animales , Cetonas/sangre , Cetonas/química , Cetonas/farmacocinética , Límite de Detección , Modelos Lineales , Masculino , Ratas , Ratas Wistar , Reproducibilidad de los Resultados
6.
Biomed Chromatogr ; 36(4): e5341, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35045589

RESUMEN

Neurotransmitters play an important role in regulating the physiological activity of the animal, especially in emotion and sleep, whereas nucleotides are involved in almost all cellular processes. However, the characteristics of sleep-related neurochemicals under different life cycles and environments remain poorly understood. A rapid and sensitive analytical method was established with LC-MS/MS to determine eight endogenous neurochemicals in Drosophila melanogaster, and their levels in the different developmental stages of D. melanogaster were evaluated. The results indicated that there were significant discrepancies among different stages, especially from the pupal stage to the adult stage. The levels of these compounds in the caffeine-induced insomnia model of D. melanogaster were investigated. Compared with the normal group, the eight endogenous metabolites did not fluctuate significantly in insomnia D. melanogaster, which may be due to the mechanism of caffeine-induced insomnia through other pathways, such as adenosine. The results provide a reference for decoding neurochemicals involved in the development of the full cycle of mammalian life and the exploration of insomnia and even other mental diseases induced by exogenous substances in the future.


Asunto(s)
Drosophila melanogaster , Trastornos del Inicio y del Mantenimiento del Sueño , Animales , Cromatografía Liquida , Drosophila melanogaster/fisiología , Mamíferos , Sueño , Espectrometría de Masas en Tándem
7.
J Sep Sci ; 44(21): 3933-3958, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34473407

RESUMEN

Baihe Dihuang decoction is a commonly used herbal formula to treat depression and insomnia in traditional Chinese medicine. This study established a liquid chromatography-mass spectrometry method to investigate the potential active ingredients and the components absorbed in the blood and brain tissue of mice. Using a new data processing method, 94 chemical components were identified, 33 and 9 of which were absorbed in the blood and brain. More interestingly, we analyzed the substance changes during co-decoction and the characteristics of the compounds absorbed in the blood and brain. The results show that 71 newly generated chemical components were discovered from co-decoction: 38 with fragment information and five absorbed in the blood. Ultimately, the results of molecular docking show that these components have excellent performance in proteins of γ-aminobutyric acid, serotonin and melatonin receptors. The docking results of emodin with Monoamine Oxidase A and Melatonin Receptor 1A, and luteolin with Solute Carrier Family 6 Member 4, Glyoxalase I, Monoamine Oxidase B and Melatonin Receptor 1A, may explain the mechanism of action of Baihe Dihuang decoction in treating insomnia and depression. Overall, our research results may provide novel perspectives for further understanding of the effective substances in Baihe Dihuang decoction.


Asunto(s)
Cromatografía Liquida/métodos , Medicamentos Herbarios Chinos , Espectrometría de Masas/métodos , Animales , Medicamentos Herbarios Chinos/análisis , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/metabolismo , Masculino , Ratones , Ratones Endogámicos ICR , Simulación del Acoplamiento Molecular
8.
Zhongguo Zhong Yao Za Zhi ; 46(1): 237-246, 2021 Jan.
Artículo en Zh | MEDLINE | ID: mdl-33645075

RESUMEN

To systematically evaluate the clinical efficacy and safety of Danhong Injection combined with conventional therapy in improving diabetes mellitus complicated with coronary heart disease. Based on the online literature database(CNKI, Wanfang, VIP, PubMed, Web of Science, Cochran Library), the Chinese and English papers about the randomized controlled trial(RCT) of Danhong Injection in the treatment of diabetes mellitus complicated with coronary heart disease were searched comprehensively from the establishment of the databases to January 1, 2020. The papers were screened strictly according to the inclusion and exclusion criteria. Based on Jadad scale, the risk assessment of literature was carried out, and Meta-analysis was performed by STATA 12.0 software. Seventeen RCTs were included, involving 1 453 patients. The results of Meta-analysis showed that the combination of Danhong Injection and conventio-nal treatment could improve the clinical comprehensive effective rate(RR=1.47, 95%CI[1.38, 1.58], P<0.000 1), electrocardiogram(ECG) efficiency(RR=1.30, 95%CI[1.16, 1.46], P<0.000 1), efficiency of the angina pectoris(RR=1.41, 95%CI[1.25, 1.58], P<0.000 1), cholesterol level(SMD=-1.05, 95%CI[-1.95,-0.16], P=0.02), low-density lipoprotein(LDL) level(SMD=-0.50, 95%CI[-0.79,-0.21], P<0.000 1), coronary angina attack frequency(SMD=-3.71, 95%CI[-4.05,-3.36], P<0.000 1) and duration of angina pectoris(SMD=-2.96, 95%CI[-3.25,-2.66], P<0.000 1), with statistically significant differences. But the differences in fasting plasma glucose(FPG)(SMD=-0.19, 95%CI[-0.45, 0.08], P=0.16), plasma glucose of two hours after meal(2 hPG)(SMD=0.19, 95%CI[-0.11, 0.49], P=0.22), and high-density lipoprotein(HDL) level(SMD=0.10, 95%CI[-0.30, 0.49], P=0.62) after treatment were not statistically significant. Compared with the control group, there was no significant difference in adverse reactions(SMD=-2.96, 95%CI[-3.25,-2.66], P=0.75). The existing evidence shows that the combination of Western medicine and Danhong Injection can improve the clinical effect for diabetes mellitus complicated with coronary heart disease and has no obvious adverse reactions. However, due to the low level of overall literature evidence, high risk and some kind of publication bias, it still needs more high-quality randomized controlled trials and low-bias studies for further verification.


Asunto(s)
Enfermedad Coronaria , Diabetes Mellitus , Medicamentos Herbarios Chinos , Angina de Pecho , Enfermedad Coronaria/complicaciones , Enfermedad Coronaria/tratamiento farmacológico , Humanos
9.
Electrophoresis ; 41(13-14): 1253-1260, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32350876

RESUMEN

In this work, we utilized adsorbed BSA and multiwalled carbon nanoparticles (BSA/MWCNTs) as a stationary phase in open tubular (OT) capillary for separation of chiral drugs. (3-Aminopropyl)triethoxysilane was used to assist fabrication of BSA/MWCNTs-coated OT column by covalent bonding. Incorporation of MWCNTs nanomaterials into a polymer matrix could increase the phase ratio and take advantage of the easy preparation of an open tubular CEC column. SEM was carried out to characterize the BSA/MWCNTs OT columns. The electrochromatographic performance of the OT columns was evaluated by separation of ketoprofen, ibuprofen, uniconazole, and hesperidin. The effects of MWCNTs concentration, background solution pH and concentration, and applied voltage on separation were investigated. Chiral separations of ketoprofen, ibuprofen, uniconazole, and hesperidin were achieved using the BSA/MWCNTs-coated OT column with resolutions of 24.20, 12.81, 1.50, and 1.85, respectively. Their optimas were found in the 30 mM phosphate buffers at pH 5.0, 6.5, 7.0, and 6.5, respectively. In addition, the columns demonstrated good repeatability and stability with the run-to-run, day-to-day, and batch-to-batch RSDs of migration times less than 3.5%.


Asunto(s)
Electrocromatografía Capilar/métodos , Nanotubos de Carbono/química , Albúmina Sérica Bovina/química , Electrocromatografía Capilar/instrumentación , Preparaciones Farmacéuticas/análisis , Preparaciones Farmacéuticas/química , Preparaciones Farmacéuticas/aislamiento & purificación , Estabilidad Proteica , Reproducibilidad de los Resultados , Estereoisomerismo
10.
Future Oncol ; 16(18): 1269-1287, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32356461

RESUMEN

Aim: Based on metabonomics, the metabolic markers of lung cancer patients were analyzed, combined with bioinformatics to explore the underlying disease mechanism. Materials & methods: Based on case-control design, using UPLC-Q-TOF/MS, urine metabolites were detected in discovery and validation set. Multivariate statistical analysis were performed to identify potential markers for lung cancer. A network analysis was constructed to integrate lung cancer disease targets with the above metabolic markers, and its possible mechanism and biological significance were explained. Results: A total of 35 potential markers were identified, 11 of which overlapped. Five key markers have a good linear correlation with serum biochemical indicators. Conclusion: The occurrence and development of lung cancer are closely related to disturbance of D-Glutamine and D-glutamate metabolism, amino acid imbalance. This test was registered on China clinical trial registration center (www.chictr.org.cn/index.aspx), registration number was ChiCTR1900025543.


Asunto(s)
Biología Computacional , Metabolismo Energético , Neoplasias Pulmonares/metabolismo , Metaboloma , Metabolómica , Anciano , Biomarcadores , Estudios de Casos y Controles , Cromatografía Líquida de Alta Presión , Biología Computacional/métodos , Bases de Datos Factuales , Femenino , Humanos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/orina , Masculino , Metabolómica/métodos , Persona de Mediana Edad , Curva ROC , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción
11.
Can J Physiol Pharmacol ; 98(1): 15-22, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31574240

RESUMEN

The present research was to assess the relationship between ABCB1 (G2677T/A, C3435T) polymorphisms and lipid homeostasis as well as risk of liver injury induced by atorvastatin in in-patients from China. The lipid levels (total cholesterol, high-density lipoprotein, triglycerides) as well as metabolic enzymes of hepar (glutamic-pyruvic transaminase, glutamic-oxalacetic transaminase, alkaline phosphatase, γ-glutamyl transpeptidase) in plasma for 162 patients were measured at baseline and after approximately 6 months of atorvastatin treatment. Polymorphisms of the ABCB1 gene were determined using the Snapshot technique. The associations between genetic polymorphisms and lipid levels as well as hepar indexes were evaluated at the end of medical treatment. Based on one-way ANOVA analysis, patients with the 2677GG or 3435TT genotypes showed a remarkable decrease in percentage when the level of TC was above 4.00 mmol·L-1, separately (P < 0.05). There was a significant decrease in percentage in the frequency of patients with the 2677GG genotype (low-density lipoprotein > 2.00 mmol·L-1) (P < 0.05). The level of glutamic-pyruvic transaminase in patients with the 2677GG or 3435CC genotype displayed a significantly increase in percentage, respectively (P < 0.05). The ABCB1 G-C haplotype carriers were associated with an increased risk of AILI. The results provide evidence for clinically individualised utilisation of atorvastatin for lipid homeostasis as well as risk of induced liver injury in the Chinese population.


Asunto(s)
Pueblo Asiatico/genética , Atorvastatina/efectos adversos , Homeostasis/genética , Metabolismo de los Lípidos/genética , Polimorfismo de Nucleótido Simple/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Anciano , Colesterol/genética , Femenino , Genotipo , Humanos , Lipoproteínas HDL/genética , Lipoproteínas LDL/genética , Hígado/efectos de los fármacos , Masculino , Transaminasas/genética , Triglicéridos/genética
12.
J Sep Sci ; 43(5): 946-953, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31802622

RESUMEN

Enantioselective open tubular capillary electrochromatography with carboxymethyl-ß-cyclodextrin conjugated gold nanoparticles as stationary phase was developed. This novel open tubular column was fabricated through layer-by-layer self-assembly of gold nanoparticles on a 3-mercaptopropyl-trimethoxysilane-modified fused-silica capillary and subsequent surface functionalization of the gold nanoparticles through self-assembly of 6-mercapto-ß-cyclodextrin. The 6-mercapto-ß-cyclodextrin was firstly synthesized and determined by extensive spectroscopic data. Scanning electron microscopy, energy dispersive X-ray analysis spectroscopy, and electroosmotic flow experiments were carried out to characterize the prepared open tubular column. Then, the separation effectiveness of the open tubular column was verified by two pairs of ɑ-tetralones derivatives enantiomers and two pairs of basic drug enantiomers (tramadol hydrochloride and zopiclone) as mode analytes. Factors that influence the enantioseparation were optimized, and under the optimized conditions, satisfactory separation results were obtained for the four enantiomers: compound A, compound B, tramadol hydrochloride, and zopiclone with resolutions of 3.79, 1.56, 1.03, 1.60, respectively. For the combination of gold nanoparticles and negatively charged carboxymethyl-ß-cyclodextrin, the open tubular column exhibited wider separation range for neutral and basic drugs. Moreover, the repeatability and stability of the column were studied through the run-to-run and day-to-day investigations.


Asunto(s)
Compuestos de Azabiciclo/aislamiento & purificación , Electrocromatografía Capilar/métodos , Oro/química , Nanopartículas del Metal/química , Piperazinas/aislamiento & purificación , Tetralonas/aislamiento & purificación , Tramadol/aislamiento & purificación , beta-Ciclodextrinas/química , Compuestos de Azabiciclo/química , Estructura Molecular , Tamaño de la Partícula , Piperazinas/química , Estereoisomerismo , Propiedades de Superficie , Tetralonas/química , Tramadol/química
13.
J Sep Sci ; 43(16): 3333-3348, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32496008

RESUMEN

In recent years, direct and indirect evidence has been found of the efficacy of the traditional Chinese medicine Bergenia purpurascens in treating arthritis and osteoarthritis. Several major components, such as bergenin and 11-O-galloylbergenin, have good anti-inflammatory activity. Since research on the chemical components of Bergenia purpurascens and related mechanisms for the treatment of osteoarthritis has never been performed, this study aimed to analyze the chemical components of Bergenia purpurascens through ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry technology and the UNIFI screening platform to predict the underlying mechanisms in treating osteoarthritis by analyzing the network pharmacology. In total, 43 chemical constituents were identified, mainly flavonoids (18), phenolic glycosides (13), and organic acids (7). Among them, 16 components were found in Bergenia purpurascens for the first time. Through the analysis of network pharmacology, several potential candidate targets and pathways were initially predicted, including AKT1, MAPK1, and MAPK3, as well as the apoptosis, estrogen, and MAPK signaling pathways. Bergenin, 11-O-galloylbergenin, arbutin, catechin-3-O-gallate, and other components play a synergistic role in treating osteoarthritis. This study analyzed the chemical components of Bergenia purpurascens and preliminarily revealed potential mechanisms of treating osteoarthritis, providing a basis for further evaluating the drug's efficacy.


Asunto(s)
Antiinflamatorios/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Osteoartritis/tratamiento farmacológico , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Humanos , Espectrometría de Masas , Medicina Tradicional China , Simulación del Acoplamiento Molecular , Estructura Molecular , Osteoartritis/metabolismo , Factores de Tiempo
14.
Ecotoxicol Environ Saf ; 190: 110073, 2020 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-31851898

RESUMEN

Dysosma Versipellis (DV), a traditional Chinese medicine, has the functions of eliminating phlegm, detoxification, dispersing knots . However, its serious toxicity limits its further use. Therefore, it is necessary to conduct a comprehensive toxicity study of DV, screen the basis of potential toxic substances and understand its toxic mechanism. Based on the concept of toxicological evidence chain (TEC), this study utilizes the technologies and means of chemomics, metabolomics, molecular docking and network toxicology flexibly, step by step to find the evidence of potential toxic components in the development of hepatotoxicity induced by DV, evidence of critical toxicity events, evidence of adverse outcomes, thus, a chain of toxicity evidence with reference and directivity can be organized. It further confirmed the toxic damage and potential molecular mechanism of DV. 5 potential toxic components were identified, namely, Podophyllotoxin-4-O-D-glucoside, Podorhizol, Podophyllotoxin, Podophyllotoxone and 3',4'-O,O-Didemethylpophyllotoxin. These chemical constituents affect phenylalanine metabolism, glycerophospholipid metabolism, energy metabolism and other related pathways by regulating PAH, SOD1, SOD2 and other related targets, then it induces oxidative stress, cell apoptosis, inflammatory reaction and energy consumption, which ultimately induces the occurrence of liver injury. The results of this study provide some reference for the follow-up analysis of toxicity mechanism of DV.


Asunto(s)
Berberidaceae , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Fitoquímicos/toxicidad , Animales , Apoptosis/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Masculino , Medicina Tradicional China , Metabolómica , Simulación del Acoplamiento Molecular , Estrés Oxidativo/efectos de los fármacos , Fitoquímicos/análisis , Ratas Wistar
15.
Toxicol Appl Pharmacol ; 383: 114785, 2019 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-31629732

RESUMEN

Celastrol (CS), an active triterpene derived from traditional Chinese medicine Tripterygium wilfordii Hook. f, has been used to treat chronic inflammation, arthritis and other diseases. However, it has been reported that CS can trigger cardiotoxicity and the molecular mechanism of heart injury induced by CS is not clear. Considering the wide application of Tripterygium wilfordii Hook. f in clinics, it is necessary to develop an accurate and reliable method to assess the safety of CS, and to elucidate as much as possible the mechanism of cardiotoxicity induced by CS. In this study, Ultra-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS)-based metabolomics revealed clues to the mechanism of CS-induced heart injury. Palmitic acid significantly increased in plasma from CS-treated rats, and this increase resulted in oxidative stress response in vivo. Excessive ROS further activate TNF signaling pathway and caspase family, which were obtained from the KEGG enrichment analysis of network toxicology strategy. Protein expression level of caspase-3, caspase-8, bax were significantly increased by western blot. Q-PCR also showed the similar results as western blot. It means that apoptosis plays a key role in the process of celastrol induced cardiotoxicity. Blocking this signal axis may be a potential way to protect myocardial tissue.


Asunto(s)
Cardiotoxinas/toxicidad , Redes y Vías Metabólicas/efectos de los fármacos , Metabolómica/métodos , Tripterygium/toxicidad , Triterpenos/toxicidad , Animales , Cardiotoxicidad/metabolismo , Cardiotoxinas/metabolismo , Masculino , Redes y Vías Metabólicas/fisiología , Triterpenos Pentacíclicos , Ratas , Ratas Wistar , Tripterygium/metabolismo , Triterpenos/metabolismo
16.
Drug Metab Rev ; 49(2): 105-138, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28266877

RESUMEN

Glucuronidation is a well-recognized phase II metabolic pathway for a variety of chemicals including drugs and endogenous substances. Although it is usually the secondary metabolic pathway for a compound preceded by phase I hydroxylation, glucuronidation alone could serve as the dominant metabolic pathway for many compounds, including some with high aqueous solubility. Glucuronidation involves the metabolism of parent compound by UDP-glucuronosyltransferases (UGTs) into hydrophilic and negatively charged glucuronides that cannot exit the cell without the aid of efflux transporters. Therefore, elimination of parent compound via glucuronidation in a metabolic active cell is controlled by two driving forces: the formation of glucuronides by UGT enzymes and the (polarized) excretion of these glucuronides by efflux transporters located on the cell surfaces in various drug disposition organs. Contrary to the common assumption that the glucuronides reaching the systemic circulation were destined for urinary excretion, recent evidences suggest that hepatocytes are capable of highly efficient biliary clearance of the gut-generated glucuronides. Furthermore, the biliary- and enteric-eliminated glucuronides participate into recycling schemes involving intestinal microbes, which often prolong their local and systemic exposure, albeit at low systemic concentrations. Taken together, these recent research advances indicate that although UGT determines the rate and extent of glucuronide generation, the efflux and uptake transporters determine the distribution of these glucuronides into blood and then to various organs for elimination. Recycling schemes impact the apparent plasma half-life of parent compounds and their glucuronides that reach intestinal lumen, in addition to prolonging their gut and colon exposure.


Asunto(s)
Glucurónidos/metabolismo , Glucuronosiltransferasa/metabolismo , Animales , Hepatocitos/enzimología , Hepatocitos/metabolismo , Humanos , Farmacocinética
17.
AAPS PharmSciTech ; 18(8): 3258-3273, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28584898

RESUMEN

The aim of this study was to investigate the influence of factors such as carrier type, drug/carrier ratio, binary carriers, and preparation method on the dissolution of an insoluble drug, indomethacin (IM), under supersaturation conditions. Using a solvent evaporation (SE) method, poloxamer 188 and PVP K30 showed better dissolution among the selected carriers. Furthermore, as the ratio of carriers increased (drug/carrier ratio from 1:0.5 to 1:2), the dissolution rate increased especially in almost two times poloxamer 188 solid dispersions (SDs), while the reverse results were observed for PVP K30 SDs. For the binary carrier SD, a lower dissolution was found. Under hot melt extrusion (HME), the dissolution of poloxamer 188 SD and PVP K30 SD was 0.83- and 0.94-folds lower than that using SE, respectively, while the binary carrier SD showed the best dissolution. For poloxamer 188 SDs, the drug's crystal form changed when using SE, while no crystal form change was observed using HME. IM was amorphous in PVP K30 SDs prepared by both methods. For binary carrier systems, amorphous and crystalline drugs coexisted in SD using SE, and negligible amorphous IM was in SD using HME. This study indicated that a higher amorphous proportion in SD did not correlate with higher dissolution rate, and other factors, such as carrier type, particle size, and density, were also critical.


Asunto(s)
Química Farmacéutica/métodos , Indometacina/química , Indometacina/metabolismo , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/metabolismo , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Tamaño de la Partícula , Poloxámero/química , Poloxámero/metabolismo , Solubilidad , Solventes/química , Solventes/metabolismo , Difracción de Rayos X
18.
Phys Chem Chem Phys ; 18(18): 12494-504, 2016 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-27086764

RESUMEN

A red phosphor of Sr2Si5N8:Eu(2+) powder was synthesized by a solid state reaction. The synthesized phosphor was thermally post-treated in an inert and reductive N2-H2 mixed-gas atmosphere at 300-1200 °C. The main phase of the resultant phosphor was identified as Sr2Si5N8. A passivation layer of ∼0.2 µm thickness was formed around the phosphor surface via thermal treatment. Moreover, two different luminescence centers of Eu(SrI) and Eu(SrII) in the synthesized Sr2Si5N8:Eu(2+) phosphor were proposed to be responsible for 620 nm and 670 nm emissions, respectively. More interestingly, thermal- and moisture-induced degradation of PL intensity was effectively reduced by the formation of a passivation layer around the phosphor surface, that is, the relative PL intensity recovered 99.8% of the initial intensity even after encountering thermal degradation; both moisture-induced degraded external and internal QEs were merely 1% of the initial QEs. The formed surface layer was concluded to primarily prevent the Eu(2+) activator from being oxidized, based on the systemic analysis of the mechanisms of thermal- and moisture-induced degradation.

19.
Metab Brain Dis ; 31(3): 653-61, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-26847610

RESUMEN

The aim of this study was to explore the neuroprotective effects of active compounds from Schisandra chinensis (Trucz.) Baill. (Magnoliaceae) against the D-galactose (D-gal)-induced neurotoxicity in rat. The Wistar rats were subcutaneously injected with D-gal (150 mg/(kg day)) for six weeks and orally administered with water extract or 95 % ethanol extract (partitioned with petroleum ether (PE), chloroform (CF), ethyl acetate (EA) and n-Butanol (NB), respectively) of the fruits of Schisandra chinensis simultaneously. The alteration of cognitive functions was assessed by using Morris water maze and Step-down type passive avoidance test. The results demonstrated that PE fraction was the most effective fraction to ameliorate cognitive deficits. Further biochemical examination indicated that PE could attenuate the activities decreasing of superoxide dismutase (SOD), catalase (CAT), the total antioxidant (T-AOC) induced by D-gal, and maintain the normal levels of glutathione (GSH), malondialdehyde (MDA) and nitric oxide (NO) in the serum, prefrontal cortex, striatum and hippocampus of the brain of related rat, selectively. Meanwhile, the compounds of PE fraction were also identified as mainly lignans, thus, these results suggest that lignans from the PE fraction of Schisandra chinensis represented a potential source of medicine for the treatment of the aging-associated neurodegenerative diseases.


Asunto(s)
Antioxidantes/farmacología , Encéfalo/efectos de los fármacos , Lignanos/farmacología , Fármacos Neuroprotectores/farmacología , Extractos Vegetales/farmacología , Schisandra , Animales , Reacción de Prevención/efectos de los fármacos , Encéfalo/metabolismo , Catalasa/metabolismo , Galactosa , Glutatión/metabolismo , Masculino , Malondialdehído/metabolismo , Aprendizaje por Laberinto/efectos de los fármacos , Óxido Nítrico/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo
20.
Inorg Chem ; 54(11): 5556-65, 2015 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-25993116

RESUMEN

A series of Eu(2+)- and Mn(2+)-codoped γ-AlON (Al1.7O2.1N0.3) phosphors was synthesized at 1800 °C under 0.5 MPa N2 by using the gas-pressure sintering method (GPS). Eu(2+) and Mn(2+) ions were proved to enter into γ-AlON host lattice by means of XRD, CL, and EDS measurements. Under 365 nm excitation, two emission peaks located at 472 and 517 nm, resulting from 4f(6)5d(1) → 4f(7) and (4)T1(4G) → (6)A1 electron transitions of Eu(2+) and Mn(2+), respectively, can be observed. Energy transfer from Eu(2+) to Mn(2+) was evidenced by directly observing appreciable overlap between the excitation spectrum of Mn(2+) and the emission spectrum of Eu(2+) as well as by the decreased decay time of Eu(2+) with increasing Mn(2+) concentration. The critical energy-transfer distance between Eu(2+) and Mn(2+) and the energy-transfer efficiency were also calculated. The mechanism of energy transfer was identified as a resonant type via a dipole-dipole mechanism. The external quantum efficiency was increased 7 times (from 7% for γ-AlON:Mn(2+) to 49% for γ-AlON:Mn(2+),Eu(2+) under 365 nm excitation), and color-tunable emissions from blue-green to green-yellow were also realized with the Eu(2+) → Mn(2+) energy transfer in γ-AlON.

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