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1.
Biochem Pharmacol ; 163: 416-424, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30878550

RESUMO

The therapeutic efficacy of immunosuppressive agents has been intensively studied for colitis management. We synthesized a series of andrographolide derivatives and reported their structure-activity-relationship and anti-inflammatory activity in our previous studies. Among these derivatives, compound 3b exhibited the most potent immunosuppressive activity. In the present study, we assessed the efficacy of 3b in dextran sulfate sodium (DSS)-induced model of acute colitis. Compound 3b was administered intragastrically. The therapeutic effect of 3b was evaluated using disease score and immune cell infiltration. The effect of 3b on Toll-like receptor 4/NF-κB and ß-catenin signaling was primarily determined by using immunohistochemistry staining and quantitative real-time PCR. The crosstalk between NF-κB and ß-catenin signaling was then assessed in HCT-116 cells. Treatment with 3b significantly downregulated the disease activity index and suppressed the histologic evidence of inflammation in DSS-induced model of acute colitis. Compound 3b inhibited proinflammatory cytokine expression at both the serum and transcription levels. Treatment with 3b also upregulated the number of PCNA-positive and goblet cells in the intestinal crypt and the intestinal expression of mRNA levels of ß-catenin target genes. ß-Catenin level regulation affected the antiinflammation and anti-apoptotic activities of 3b. This study demonstrated that 3b, a novel andrographolide derivative, suppressed inflammation and significantly reversed colitis pathology. The outcome of colitis treatment with an immunosuppressive agent depends upon the intestinal expression and mutation status of ß-catenin.


Assuntos
Anti-Inflamatórios/farmacologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Sulfato de Dextrana/toxicidade , Diterpenos/química , Animais , Anti-Inflamatórios/química , Células HCT116 , Humanos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Relação Estrutura-Atividade
2.
Am J Chin Med ; 43(8): 1515-24, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26621440

RESUMO

The clinical therapeutics of traditional Chinese medicine (TCM) constitutes a complicated process which involves theory, diagnosis, and formula prescription with specific herbal dosage. Zhang Zhong-Jing's classic work, Treatise on Febrile and Miscellaneous Diseases, has been influencing TCM practice for almost 2000 years. However, during this extended period of time in Chinese history, the Chinese weight measurement system experienced noticeable changes. This change in the weight measurement system inevitably, and perhaps even negatively, affected TCM herbal dosage determination and treatment outcome. Thus, in modern society, a full understanding of the accuracy of herbal dose selection has a critical importance in the TCM daily practice of delivering the best treatment to the patients suffering from different illnesses. In the 973 Project of the Chinese National Basic Research Program, expert consensus on classic TCM formula dose conversion has been reached based on extensive literature review and discussion on the dose-effect relationship of classic TCM formulas. One "liang" in classic TCM formulas is equivalent to 13.8 g. However, based on many TCM basic and clinical studies of variable herbal formula prescriptions and herbal drug preparations, the rule of one liang equals 13.8 g should be adjusted according to different disease conditions. Recommended by the committee on TCM formula dose-effect relationship of the China Association of Chinese Medicine and the World Federation of Chinese Medicine Societies, the following expert consensus has been reached: (i) One liang converts to 6-9 g for the severely and critically ill patients. (ii) One liang converts to 3-6 g for the patients suffering from chronic diseases. (iii) One liang converts to 1-3 g in preventive medicine. The above conversions should be used as a future TCM practice guideline. Using this recommended guideline should enhance the effectiveness of daily TCM practice.


Assuntos
Cálculos da Dosagem de Medicamento , Medicamentos de Ervas Chinesas/administração & dosagem , Medicina Tradicional Chinesa , Relação Dose-Resposta a Droga , Sistema Métrico , Guias de Prática Clínica como Assunto , Pesos e Medidas
3.
Zhongguo Zhong Yao Za Zhi ; 40(7): 1410-4, 2015 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-26281571

RESUMO

To analyze and discuss placebo-related information in clinical research literatures in the past 30 years, including placebo's dosage form, ingredients, preparation process and quality control. Effort were made to research the CNKI. full-text database to preliminary find 700 placebo-related clinical research literature, screen out 301 eligible articles by hand, read the literatures to extract placebo-related information and make statistics and discussions. According to the results, Chinese randomized placebo-controlled clinical studies were characterized by diverse dosage forms of placebo with lack of reports for components, as evidenced by the only 17 literatures describing placebo's preparation or specific composition among the 301 literatures. Placebo-controlled clinical trials covered a wide range of disease spectra, but with a specific tropism of diseases in terms of system classification. Although placebo plays a key role in blinded clinical studies, researchers made less records of placebo, perhaps because they paid less attention to placebo or more attention to the research process or restricted by other objective conditions. Moreover, placebo production, quality control and quality evaluation also need to be further standardized.


Assuntos
Pesquisa Biomédica/história , Efeito Placebo , Ensaios Clínicos Controlados Aleatórios como Assunto/história , Pesquisa Biomédica/normas , China , História do Século XX , História do Século XXI , Humanos , Controle de Qualidade , Ensaios Clínicos Controlados Aleatórios como Assunto/normas
4.
Guang Pu Xue Yu Guang Pu Fen Xi ; 33(5): 1392-6, 2013 May.
Artigo em Chinês | MEDLINE | ID: mdl-23905359

RESUMO

Aiming at forecasting elemental contents in geological samples accurately, a principal component analysis and improved BP (PCA-BP) neural network theory is proposed in the present work. The samples from west Tianshan were measured through X-ray fluorescence measurement method, and the X-Ray fluorescence counts of each element such as Fe, Ti, V, Pb, Zn, etc. were input to the PCA-BP neural network as input variables to forecast Fe and Ti contents in uncertified geological samples quantitatively. The results show that the PCA-BP neural network can give an ideal result, and the relative error between the forecast data and chemical analysis data is less than 3%. This method provides a new and effective approach to forecasting elemental contents in geological samples.

5.
Bioorg Med Chem Lett ; 23(3): 654-7, 2013 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-23290052

RESUMO

Two new quassinoids, altissinol A (1) and B (7), together with 12 known quassinoids, were isolated from the 95% ethanol extract of the barks of Ailanthus altissima. The structures of the new compounds (1 and 7) were determined on the basis of the spectroscopic methods including UV, IR, HR-ESI-MS, 1D and 2D NMR. The cytotoxic potential of all isolates were evaluated in vitro against three human hepatoma cell lines. Quassinoids 1-7 displayed potent cytotoxic activities against human hepatoma Hep3B and HepG2 cell lines. Interestingly, compounds 2, 3, and 5 exhibited cytotoxic activity against multidrug resistance HepG2/ADM cell line with IC(50) value 4.3-fold more sensitive to Doxorubicin (DOX).


Assuntos
Ailanthus/química , Casca de Planta/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Quassinas/química , Quassinas/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/farmacologia , Células Hep G2 , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Estrutura Molecular
6.
Am J Chin Med ; 41(1): 33-42, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23336505

RESUMO

A prospective multicenter clinical trial was conducted to compare the beneficial effects of a Chinese herbal medicine formula Jiangzhuoqinggan (JZQG) and western antihypertension drug irbesartan. JZQG is mainly composed of rhubarb, coptis, cassia, and uncaria. A total of 240 patients with mild to moderate hypertension were enrolled in the trial. Patients were assigned into two groups after screening: JZQG group and the irbesartan group. After four weeks of treatment, we compared the changes in routine blood pressure, 24 h ambulatory blood pressure, and waist circumference. There was a significant reduction in systolic blood pressure and diastolic blood pressure in the JZQG group (both p < 0.01). There were no significant differences between the reduction of systolic and diastolic blood pressures in the two treatment groups. From the 24 h ambulatory blood pressure measurement, the JZQG group showed a greater reduction in both systolic and diastolic blood pressures (in both daytime and nighttime) than the irbesartan group. Furthermore, there was a significant difference in waist circumference in the JZQG group (1.51 cm reduction; P < 0.05) but not the irbesartan group (0.42 cm). Thus, the JZQG formula may have therapeutic value in patients with both hypertension and metabolic syndrome.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Hipertensão/tratamento farmacológico , Adolescente , Adulto , Idoso , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Compostos de Bifenilo/farmacologia , Compostos de Bifenilo/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Humanos , Irbesartana , Masculino , Síndrome Metabólica/tratamento farmacológico , Pessoa de Meia-Idade , Estudos Prospectivos , Tetrazóis/farmacologia , Tetrazóis/uso terapêutico , Circunferência da Cintura/efeitos dos fármacos , Adulto Jovem
7.
Toxicon ; 47(2): 241-8, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16386281

RESUMO

A novel metalloproteinase, recombinant fibrinogenase IV (rFIV(a)), was expressed and purified from Deinakistrodon acutus venom. It was a single chain protein with an apparent molecular weight 27 kDa and an isoeletric point of pH 7.1. RFIV(a) cleaved preferentially the Aalpha-chain and also cleaved Bbeta, gamma-chains of fibrinogen when the incubation time was prolonged. The proteolytic activity was inhibited by EDTA, l-cysteine, and DTT, indicating rFIV(a) was a metalloproteinase requiring disulfide bonds for its activity. It kept above 85% of the initial activity from pH 4.5-11, showed an equal maximum activity at the temperature range from 30 to 50 degrees C, and was inactivated by Zn2+, Cu2+ and Cd2+. Homology modeling of rFIV(a) showed that two highly conserved disulfide bonds (Cys159-Cys164 and Cys117-Cys197) was maintained from its structure, and it exhibited the characteristic conserved motif H142E143XXH146XXGXXH152, whose three histidine residues were involved in binding of the catalytically essential zinc ion. This work demonstrates the expression, purification and characterization of recombinant fibrinogenase IV, which belongs to class P-I metalloproteinase from D. acutus venom.


Assuntos
Fibrinogênio/metabolismo , Metaloproteases/química , Metaloproteases/isolamento & purificação , Modelos Moleculares , Venenos de Serpentes/enzimologia , Serpentes , Sequência de Aminoácidos , Animais , Estabilidade Enzimática , Expressão Gênica , Concentração de Íons de Hidrogênio , Metaloproteases/metabolismo , Conformação Proteica , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Temperatura
8.
Appl Microbiol Biotechnol ; 72(1): 72-76, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16429282

RESUMO

A novel metalloproteinase, recombinant fibrinogenase IV (rFIVa), was expressed and purified from Agkistrodon acutus venom. It is a single-chain protein with an apparent molecular weight of 27 kDa. Western blot showed that it had a good immunological reaction against anti-FIVa rabbit serum. The kinetic parameters Km and Kcat of rFIVa on the substrate T6140 were 7.471 x 10(-4) mol/l and 5.103 x 10(-5) s(-1). RFIVa cleaved preferentially the alpha-chain, and the beta- and gamma-chains of fibrinogen were also cleaved when the incubation time was prolonged. The administration of rFIVa (1.8 and 5.4 mg/kg) to animals with acute blood-stasis model produced a decrease in fibrinogen to control values. To our knowledge, this is the first report of the expression, purification, and evaluation of recombinant fibrinogenase IV, which belongs to class P-I metalloproteinase from A. acutus venom.


Assuntos
Agkistrodon , Venenos de Crotalídeos/enzimologia , Serina Endopeptidases/biossíntese , Animais , Western Blotting , Clonagem Molecular , Fibrinogênio/metabolismo , Cinética , Modelos Animais , Peso Molecular , Ratos , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Serina Endopeptidases/química , Serina Endopeptidases/genética , Leveduras/genética , Leveduras/metabolismo
9.
Sheng Li Xue Bao ; 56(3): 313-20, 2004 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-15224143

RESUMO

To investigate the inhibition of cyclosporin A (CsA) on neutrophil adhesion to human umbilical vein endothelial cells (HUVECs, ECV-304) induced by hypoxia/reoxygenation and further explore its mechanism, a 1 h hypoxia/4 h reoxygenation model was reproduced using ECV-304. The adhesion rate of neutrophils to ECV-304 was determined by measuring the activity of endogenous hexosaminidase. The expression of endothelial cell adhesion molecules of E-selectin and ICAM-1 was measured by flow cytometry. The expression of cyclophilin A (CyPA) and the activation of ERK1/2 was compared among experimental groups by Western blot. The content of reactive oxygen species (ROS) was measured by Fenton reaction. After being stimulated with 1 h hypoxia/4 h reoxygenation, ECV-304 showed an enhanced neutrophil adhensiveness in association with an increased surface expression of E-selectin and ICAM-1. In parallel, the content of ROS was also increased. These effects were significantly suppressed by the addition of CsA. Most importantly, the expression of CyPA was significantly increased following 1 h hypoxia/4 h reoxygenation, which was accompanied with an increased activation of ERK1/2. Treatment with CyPA inhibitor CsA and CyPA antisense oligonucleotides significantly inhibited the activation of ERK1/2 and decreased the adhesion of neutrophils to ECV-304. The specific ERK1/2 inhibitor PD98059 caused an inhibition of neutrophil adhesion to hypoxia/reoxygenation-stimulated ECV-304. Our data confirm that CsA inhibits neutrophil adhesion to hypoxia/reoxygenation stimulated ECV-304 by a mechanism involving inhibition of the signal transduction of ROS, CyPA and ERK1/2.


Assuntos
Ciclofilinas/biossíntese , Ciclosporina/farmacologia , Endotélio Vascular/citologia , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Neutrófilos/citologia , Adesão Celular , Hipóxia Celular , Células Cultivadas , Ciclofilinas/genética , Humanos , Molécula 1 de Adesão Intercelular/biossíntese , Molécula 1 de Adesão Intercelular/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/fisiopatologia , Transdução de Sinais , Veias Umbilicais/citologia
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