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2.
Nihon Yakurigaku Zasshi ; 154(5): 275-287, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31735758

RESUMO

Brexpiprazole (Rexulti®) is the second antipsychotic agent in the world with dopamine D2 receptor partial agonist which was developed by Otsuka Pharmaceutical Co. Ltd. It is categorized as 〝Serotonin- dopamine Activity Modulator (SDAM)〟 that regulates both serotoninergic and dopaminergic systems by acting as a partial agonist for serotonin 5-HT1A receptors and D2 receptors and as an antagonist for 5-HT2A receptors. In preclinical pharmacological studies, brexpiprazole showed the equivalent antipsychotic-like effects to those of other atypical antipsychotics. And it was suggested that brexpiprazole has the low potentials to induce extrapyramidal symptoms, hyperprolactinemia and tardive dyskinesia, with improvement effects on cognitive dysfunction. Furthermore, brexpiprazole has the weak effects on histamine H1 receptors which are associated with sedation and weight gain in clinical. In the clinical trials in patients with schizophrenia in both acute and maintenance phase, brexpiprazole showed improvement of antipsychotic effects against placebo, and low incidence of adverse events, e.g., extrapyramidal symptoms, hyperprolactinemia, and weight gain, as suggested in preclinical studies. Furthermore, brexpiprazole showed low incidence of metabolic abnormalities. In particular, brexpiprazole showed relatively low incidences of akathisia, insomnia and agitation which has been commonly reported with aripiprazole. This would be based on the pharmacological features of brexpiprazole that is more potent antagonism at 5-HT2A receptors and D2 receptors partial agonism with lower intrinsic activity compared to those of aripiprazole. In conclusion, brexpiprazole could be one of the antipsychotics with the most rational mechanism of action, and the better efficacy and safety/tolerability profiles would contribute to the treatment of patients with schizophrenia.


Assuntos
Antipsicóticos/farmacologia , Quinolonas/farmacologia , Tiofenos/farmacologia , Ensaios Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Humanos , Esquizofrenia/tratamento farmacológico , Comprimidos , Resultado do Tratamento
3.
Se Pu ; 37(11): 1200-1208, 2019 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-31642273

RESUMO

The control mode of standard preparation (SP) and quantitative high performance liquid chromatography (HPLC) fingerprint of Fufanggancao tablets (FFGCTs) combined with the quantification of five markers were successfully developed and applied to the precise and accurate assessment of the quality consistency of 145 FFGCTs from nine manufacturers. The profiling was determined by reversed-phase HPLC at 220 nm wavelength, where the reference fingerprint (RFP) of the FFGCTs reserved as standard preparation was established. Subsequently, the SP-RFP was considered as the evaluation standard, and a systematic quantitative fingerprint method was applied to the integrative quality discrimination of 145 batches of FFGCTs, from both qualitative and quantitative perspectives. Besides, the chromatographic systematic error of quantitative fingerprints was corrected by the double marker calibration method. The results showed that the qualities of the FFGCTs from the nine manufacturers were completely qualified. Moreover, all raw herb fingerprints and the simulated sample were determined by using the combined chromatographic conditions applied to the FFGCTs, which helped identify the source of the profiling peaks in the preparation and establish the correlation between the raw herb fingerprints and the preparation fingerprints. This eventually aided the intelligent prediction of the quality of the preparation or raw herbs and effective prevention of the inputs of inferior raw materials. In addition, we employed the ultraviolet full fingerprint dissolution method to differentiate the FFGCTs from five manufacturer dissolution, in which the rationality of the preparation process was evaluated. The method is feasible and accurate, and it can be applied to evaluate the quality and process technology consistency of FFGCTs. This paper provides a fundamental standard preparation evaluation mode and the basic operation procedure for the quality consistency assessment of traditional Chinese medicine.


Assuntos
Medicamentos de Ervas Chinesas/análise , Controle de Qualidade , Cromatografia Líquida de Alta Pressão , Medicina Tradicional Chinesa , Comprimidos
4.
Se Pu ; 37(11): 1209-1214, 2019 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-31642274

RESUMO

Radial thin-layer chromatography (RTLC) is a form of chromatography in which the sample and developing agent/solvent are applied at the edge of a circle on the silica-layered TLC plate. The sample components are radially transported from the center of the circle toward the periphery by the solvent flow. RTLC is an efficient separation and semi-preparation method, with the advantages of fast separation, low diffusion, and absence of tailing at a certain distance. Although RTLC isolation has been well documented in the literature, there are only a few qualitative and quantitative reports on this technique. In this study, a self-programming module combined with image processing software was adopted for digital processing of RTLC images, and a digital atlas was created. Qualitative and quantitative verification of RTLC was then conducted. With the aid of computer technology, qualitative and quantitative methods of radially expanded TLC for Yiqing tablets were investigated. The results showed that the qualitative RTLC method has good reliability, but the quantitative RTLC method has inherent drawbacks, which may be associated with the experimental environment. We strongly believe that better separation and data acquisition equipment, as well as the combination of computer image processing and programming methods, will open up infinite possibilities of analysis/separation using RTLC-based techniques. We also believe that TLC will take a new step in the future with the assistance of computer technology.


Assuntos
Cromatografia em Camada Delgada/instrumentação , Medicamentos de Ervas Chinesas/análise , Processamento de Imagem Assistida por Computador , Reprodutibilidade dos Testes , Solventes , Comprimidos
5.
Se Pu ; 37(11): 1235-1240, 2019 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-31642278

RESUMO

A gas chromatographic fingerprint combined with chemical pattern recognition was successfully developed and applied to assess the quality consistency of 20 Chenxianghuaqi tablets. Volatile components from the 20 Chenxianghuaqi tablets were extracted with ethanol under ultrasonic conditions. n-Octadecane was used as the internal standard to calculate the amounts of the three main components and to confirm the relative peak areas of the other components. Gas chromatographic fingerprints of the 20 Chenxianghuaqi tablets were established. There were 11 common peaks in the fingerprints, and the similarity of each batch of samples was obtained. Ten common peaks were identified by gas chromatography-mass spectrometry, with reference comparison. The obtained fingerprints were used for the chemical pattern recognition, including hierarchical cluster analysis and the principal component analysis. Different batches of Chenxianghuaqi tablets could be differentiated effectively, and major markers that led to differences among the sample batches were identified. The method proposed in this study is comprehensive and reliable, and it can be used as a valuable reference to evaluate and control the quality of Chenxianghuaqi tablets.


Assuntos
Medicamentos de Ervas Chinesas/análise , Controle de Qualidade , Cromatografia Gasosa-Espectrometria de Massas , Comprimidos
6.
Zhongguo Zhong Yao Za Zhi ; 44(14): 2943-2946, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31602837

RESUMO

Hugan Tablets is a Chinese patent medicine,it has the function of anti-inflammation and reducing transaminase. Based on questionnaire investigation of doctors and a systematic review of research literature on Hugan Tablets,using international clinical practice guidelines' developing methods,with the best available evidence and fully combining expert experience,and following the principle of " evidence-based,consensus-based and experience-based",Expert consensus statement on Hugan Tablets in clinical practice was developed by more than 30 multidisciplinary experts from the nationwide,aimed at guiding and standardizing the rational use of Hugan Tablets by clinicians and to improve clinical efficacy and safety. The expert consensus adopts internationally recognized recommendation criteria for classification of evidence: GRADE. The formation of expert consensus adopts the nominal group technique. Six main considerations are quality of evidence,curative effect,safety,economical efficiency,patient acceptability and other factors. If there is sufficient evidence,a " recommendation" is formed,using GRADE grid voting rule. If there isn' t sufficient evidence,a " consensus opinion" is formed,using majority counting rule. Focus on the indication,usage and dosage,drug use in special population and safety of Hugan Tablets,two recommendations and eight consensus opinions were put forward. Through expert meetings and correspondence,a nationwide consultation and peer review was conducted. This consensus applies to clinicians in hospitals and grass-roots health services,to provide guidance and reference for the rational use of Hugan Tablets.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Inflamação/tratamento farmacológico , Consenso , Humanos , Medicamentos sem Prescrição , Comprimidos
7.
Zhongguo Zhong Yao Za Zhi ; 44(14): 3035-3041, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31602850

RESUMO

The taste is the key to the research and design for formulation prescription of traditional Chinese medicine buccal tablets( TCMBTs). TCMBTs are dissolved in the oral cavity in parallel with the release of the drug,providing a sufficient " time window" for the perception of various basic taste,tactile and retention. The overall taste is the result of competitive inhibition,comprehensive superposition and dynamic change of multiple tastes. Traditional evaluation methods rely mostly on recalled experience score,difficult to reflect the dynamic changes of taste for buccal tablets. Therefore,it is urgent to establish a new optimized model for taste evaluation and formulation prescription according to the formulation characteristics of TCMBTs. To this end,this paper proposed for the first time to construct a research method for the optimal formulation of TCMBTs based on temporal dominant description of sensations combined with multivariate statistical analysis: the sensory test of volunteers was carried out by temporal dominant description analysis method,and elements separation was conducted for the time and taste in the process of inclusion to form a temporal dominant descriptive score of multi-time points and multi-sensory attributes. Finally,the optimal formulation was obtained by multivariate statistical analysis. Taking the formulation prescription of Compound Caoshanhu Buccal Tablets as an example,the research ideas of this method were explained,and the optimal formulation prescription was obtained as follows,Glabrous Sarcandra Extract of 20. 0 g,mannitol of 24. 0 g,microcrystalline cellulose of 12. 0 g,aspartame of 1. 0%,menthol of 0. 7%,and menthol oil of 0. 7%. This study provides a new method for the taste evaluation and formulation research of TCMBTs,providing a new idea for the fine manufacturing and innovative development of TCM buccal tablets in the new era.


Assuntos
Composição de Medicamentos , Comprimidos , Paladar , Humanos , Medicina Tradicional Chinesa , Sensação , Solubilidade
8.
Eur J Pharm Biopharm ; 145: 35-41, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31568821

RESUMO

Film coating of nifedipine tablets is commonly performed to reduce photo-degradation. The coating thickness of these tablets is a primary dictating factor of photo-stability. Terahertz spectroscopy enables accurate measurement of coating thickness. This study identifies a method to determine an end-point of a photo-protective coating process by using coating thickness measurements from terahertz time of flight spectroscopy (THz-TOF). For this method, nifedipine tablets, at different coating thicknesses, were placed in a photostability chamber. The illumination conditions of the coated tablets were adjusted based on the time duration of these tablets inside the chamber. A multiple linear regression model was developed with the coating thickness estimates from THz-TOF and illumination conditions information to predict the amount of drug remaining after photo-degradation (percent label claim). The prediction error of this model was 1.03% label claim in the range of 88.4-100.6% label claim. According to this model, acceptable levels of photo-protection in illumination conditions of up to approximately 700,000 lx hours was achieved at the end of the coating process (approximately 50 µm coating thickness) performed in this study. These results suggest THz-TOF as a viable process analytical technology tool for process understanding and end-point determination of a photo-protective coating process.


Assuntos
Nifedipino/química , Fotólise/efeitos dos fármacos , Comprimidos com Revestimento Entérico/química , Comprimidos/química , Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Excipientes/química , Propriedades de Superfície/efeitos dos fármacos , Imagem Terahertz/métodos
9.
Eur J Pharm Biopharm ; 145: 7-11, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31605741

RESUMO

The usefulness, the high production rate and the cost effectiveness make tablets the dosage form of choice for oral probiotics. Nevertheless, probiotic bacteria undergo a lot of mechanical stress during tableting which causes damage to their cell wall and membrane and other bio-active components. This can lead to an inactivation of the probiotic bacteria and therefore in a failure of the probiotic therapy. To obtain a tablet with a sufficient amount of viable cells, research on the influence of formulation and process parameters on bacterial survival is essential. This study aimed to decipher tableting properties of the probiotic powder blends that have a major impact on survival rates. The powder blends consisted of the prototype probiotic strain Lactobacillus rhamnosus GG, a filler-binder and a suitable amount of lubricant. They were manufactured by direct compression at different compression pressures and tableting speeds. The tableting properties were analysed in detail by a 3-D modelling technique, which characterized normalized time, pressure and displacement simultaneously. The results of the 3-D modelling demonstrated the significant effect of the pressure plasticity (e) and the angle of rotation (ω) on the viability of L. rhamnosus GG during direct compression.


Assuntos
Força Compressiva/efeitos dos fármacos , Probióticos/química , Comprimidos/química , Química Farmacêutica/métodos , Excipientes/química , Lactobacillus rhamnosus/química , Pós/química , Pressão
10.
Chem Pharm Bull (Tokyo) ; 67(10): 1144-1151, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31582634

RESUMO

Definitive screening design (DSD) is a new class of small three-level experimental design that is attracting much attention as a technical tool of a quality by design (QbD) approach. The purpose of this study is to examine the usefulness of DSD for QbD through a pharmaceutical study on the preparation of ethenzamide-containing orally disintegrating tablet. Model tablets were prepared by directly compressing the mixture of the active pharmaceutical ingredient (API) and excipients. The five evaluated factors assigned to DSD were: the contents of API (X1) and lubricant (X2), and the compression force (X3) of the tableting process, the mixing time (X4), and the filling ratio of powder in the V-type mixer (X5). After tablet preparation, hardness and disintegration time were measured. The same experiments were performed by using the conventional design of experiments [i.e., L8 and L16 orthogonal array designs and central composite design (CCD)]. Results showed that DSD successfully clarified how various factors contribute to tablet properties. Moreover, the analysis result from DSD agreed well with those from the L8 and L16 experiments. In additional experiments, response surfaces for tablet properties were created by DSD. Compared with the response surfaces created by CCD, DSD could produce reliable response surfaces for its smaller number of experiments. We conclude that DSD is a powerful tool for implementing pharmaceutical studies including the QbD approach.


Assuntos
Desenho de Drogas , Preparações Farmacêuticas/química , Composição de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Preparações Farmacêuticas/administração & dosagem , Propriedades de Superfície , Comprimidos/administração & dosagem , Comprimidos/química
11.
Chem Pharm Bull (Tokyo) ; 67(10): 1152-1159, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31582635

RESUMO

Melt adsorption is a manufacturing method that offers precise control of particle size distribution of granules and circumvents the disadvantages of conventional melt granulation. However, drug release from particles adsorbed with hydrophobic materials has not been fully investigated, and there are missing details as to whether particles manufactured by this technique can be applied to orally disintegrating tablets (ODT). In this report, we aimed to optimize process parameters and formulation to manufacture ODT containing melt adsorption-particles with the specific characteristic of sustained release. Melt adsorption particles containing Neusilin US2 as the adsorbent were prepared by using various waxes to determine the most suitable material for controlled release formulation. Glycerol fatty acid ester (Poem TR-FB: TR-FB) was the optimal wax examined because of its drug release pattern and tabletability. We then optimized manufacturing conditions by examining granulation time, disintegrant amount per tablet and compression force on the tablet for ODT that meet the criteria of controlled drug release, tensile strength and disintegration of the tablet. Multiple regression analysis revealed the effect of process parameters on tablet properties and drug release with increasing the granulation time affording sustained release of the drug. The analysis also showed that a high compression force crushed the granules coated by TR-FB, which impaired sustained drug release. From the regression model the optimal manufacturing conditions were determined, and the tablet prepared under these conditions concurred with the predicted values and met all criteria. This new technique should contribute to the development of ODT to improve medication adherence.


Assuntos
Compostos de Alumínio/química , Compostos de Magnésio/química , Silicatos/química , Administração Oral , Adsorção , Ésteres/química , Ácidos Graxos/química , Glicerol/química , Interações Hidrofóbicas e Hidrofílicas , Tamanho da Partícula , Propriedades de Superfície , Comprimidos/administração & dosagem , Comprimidos/química
12.
Expert Rev Clin Pharmacol ; 12(11): 1013-1018, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31639317

RESUMO

Introduction: Lambert-Eaton myasthenic syndrome is an autoimmune disease of the neuromuscular junction characterized by a presynaptic defect of neuromuscular transmission resulting in muscle weakness and fatigability. Diagnostic features are specific neurophysiological alterations and autoantibody detection. The present review is focused on the use of Amifampridine Phosphate to treat LEMS patients.Areas covered: Medline search from 1990 to 2019 was examined using the free subject terms: Lambert-Eaton myasthenic syndrome, LEMS, Amifampridine, 3,4-diaminopyridine, which were then combined with Treatment, Therapy, Clinical Trial, Controlled Clinical Trial, Randomized Clinical Trial and Cochrane Review. The author has done a supervised analysis of the retrieved articles and focused on those subjectively evaluated as most relevant.Expert commentary: Data from randomized clinical trials and case series have demonstrated that Lambert-Eaton myasthenic syndrome symptoms were successfully treated by Amifampridine Phosphate. Hence, the drug represents a substantial step forward in the symptomatic treatment of the disease due to its efficacy, safety and reliable GMP formulation. As Amifampridine Phosphate works by enhancing the release of acetylcholine at the neuromuscular junction by blocking K+ efflux at the pre-synaptic membrane, it is also conceivable to use it for other diseases of the neuromuscular junction in which such an effect is searched for.


Assuntos
Amifampridina/administração & dosagem , Síndrome Miastênica de Lambert-Eaton/tratamento farmacológico , Fármacos Neuromusculares/administração & dosagem , Amifampridina/efeitos adversos , Amifampridina/farmacologia , Humanos , Síndrome Miastênica de Lambert-Eaton/fisiopatologia , Fármacos Neuromusculares/efeitos adversos , Fármacos Neuromusculares/farmacologia , Bloqueadores dos Canais de Potássio/administração & dosagem , Bloqueadores dos Canais de Potássio/efeitos adversos , Bloqueadores dos Canais de Potássio/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Comprimidos
14.
Zhongguo Zhong Yao Za Zhi ; 44(15): 3358-3364, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602895

RESUMO

To evaluate the effect of Tripterygium Glycosides Tablets extract in the treatment of rheumatoid arthritis( RA). Clinical trials of treating rheumatoid arthritis with Tripterygium Glycosides Tablets published by Meta-analysis were retrieved from EMbase,PubMed,Clinical Trials,Web of Science,Cochrane Library,CNKI,Wanfang,VIP,CBM and Chi CTR,and comprehensively analyzed. A total of 3 studies were enrolled,the modified Sharp score( m TSS),tender join joint erosions( JE) and joint space narrowing( JSN) of Tripterygium Glycosides Tablets group were significant superior to those of control group,including positive drugs methotrexate( MTX) and salazopyridine( SSZ)( P<0. 01). Tripterygium Glycosides Tablets had an effect in treating RA. Due to the small sample size,this study shall be verified with high-quality,large-sample-size double-blinded RCTs.


Assuntos
Antirreumáticos/farmacologia , Artrite Reumatoide/tratamento farmacológico , Glicosídeos/farmacologia , Tripterygium/química , Humanos , Comprimidos
15.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3368-3373, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602897

RESUMO

Tripterygium wilfordii preparations,with various biological activities such as immunosuppressive,anti-inflammatory and anti-cancer effects,are widely used in the treatment of autoimmune diseases such as rheumatoid arthritis,lupus erythematosus,and nephrotic syndrome. They have definite therapeutic effect,but often cause serious adverse reactions and result in damages to liver,kidney,blood,reproduction,and other systems due to their complex compositions,great toxicity,and narrow margin between the toxic and therapeutic dosages. At present,T. wilfordii preparations produced by different manufacturers exhibit large variations in clinical efficacy and side effects in account of their different chemical compositions and quality fluctuation due to differences in raw materials and production process. However,the existing quality standards are controversial in terms of index components and content limit,which cannot be effectively used for the overall quality control of the preparations. In this paper,the research progress on chemical constituents,quality standard and quality control methods of four T. wilfordii preparations including Tripterygium Tablets,Tripterygium Zongtie Tablets,Tripterygium Shuangceng Tablets and Tripterygium Glycosides Tablets was reviewed,in order to provide ideas and reference for the quality improvement of this type of preparations.


Assuntos
Medicamentos de Ervas Chinesas/normas , Controle de Qualidade , Tripterygium/química , Comprimidos
16.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3415-3422, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602903

RESUMO

Growing clinical evidence shows that a partial rheumatoid arthritis( RA) patient treated with Tripterygium Glycosides Tablets( TGT) may fail to achieve clinical improvement. It is of great clinical significance to predict the therapeutic effect of TGT in RA. Therefore,the aim of the current study was to identify potential biomarkers for TGT treatment in RA. Affymetrix EG1.0 arrays were applied to detect gene expression in peripheral blood mononuclear cells obtained from 6 RA patients( 3 responders and 3 non-responders) treated with TGT. By integrating differential expression data analysis and biomolecular network analysis,360 mRNAs( 185 up-regulated and 175 down-regulated) and 24 miRNAs( 7 up-regulated and 17 down-regulated) which were differentially expressed between TGT responder and non-responder groups were identified. A total of 206 candidate target genes for the differentially expressed miRNAs were obtained based on miRanada and Target Scan databases,and then the miRNA target gene coexpression network and miRNA-mediated gene signal transduction network were constructed. Following the network analyses,three candidate miRNAs biomarkers( hsa-miR-4720-5 p,hsa-miR-374 b-5 p,hsa-miR-185-3 p) were identified as candidate biomarkers predicting individual response to TGT. Partialleast-squares( PLS) was applied to construct a model for predicting response to TGT based on the expression levels of the candidate gene biomarkers in RA patients. The five-fold cross-validation showed that the prediction accuracy( ACC) of this PLS-based model efficacy was 100.00%,100.00%,100.00%,66.67% and 66.67% respectively,and all the area under the receiver operating characteristic curve( AUC) were 1.00,indicating the highly predictive efficiency of this PLS-based model. In conclusion,the integrating transcription data mining and biomolecular network investigation show that hsa-mir-4720-5 p,hsa-mir-374 b-5 p and hsa-mir-185-3 p may be candidate biomarkers predicting individual response to TGT. In addition,the PLS model based on the expression levels of these candidate biomarkers may be helpful for the clinical screen of RA patients,which potentially benefit individualized therapy of RA in a daily clinical setting.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Glicosídeos/uso terapêutico , MicroRNAs/genética , Tripterygium/química , Biomarcadores , Mineração de Dados , Humanos , Leucócitos Mononucleares , Comprimidos
17.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3441-3447, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602907

RESUMO

To observe the effect of Tripterygium Glycosides Tablets on angiogenesis of rats with type Ⅱ collagen-induced arthritis( CIA) and on the tube formation of human umbilical vein endothelial cells( HUVEC) in vitro. The HUVEC were induced by 20 µg·L-1 vascular endothelial growth factor( VEGF) in vitro,and were treated with 0. 1,1,10 mg·L-1 Tripterygium Glycosides Tablets continuously for 7 hours. The numbers of branches of tube formation were measured. SD rats were immunized to establish CIA. CIA rats were treated with 9,18,36 mg·kg-1·d-1 Tripterygium Glycosides Tablets for 42 days. Histopathological examination( HE) was performed to observe the vascular morphology and vascular density in the synovial membrane of the inflamed joints. Immunohistochemistry and immunofluorescence were performed to observe the expression of platelets-endothelial cell adhesion molecule( CD31) and αsmooth muscle actin( αSMA) in synovial membrane. Immunohistochemistry and Western blot were performed to observe the expression of hypoxia-inducible factors 1α( HIF1α) and angiotensin 1( Ang1) in the synovial tissue. The results showed that the numbers of branches of tube formation of HUVEC induced by VEGF were improved,and declined significantly after treated by Tripterygium Glycosides Tablets. Compared with the normal group,the vascular density,CD31 positive expression,CD31 +/αSMA-immature and total vascular positive expression in the synovial membrane of the model group were significantly increased,and so as HIF1α and Ang1 in the synovium. Tripterygium Glycosides Tablets reduced the synovial vascular density and inhibited the positive expression of CD31,CD31+/αSMA-immature blood vessels and total vascular,but has no effect on CD31+/αSMA+mature blood vessels. Tripterygium Glycosides Tablets also inhibited the expression of HIF1α and Ang1 in synovial membrane of inflammatory joints. Our results demonstrated that Tripterygium Glycosides Tablets could inhibit the angiogenesis of synovial tissue in CIA rats and the tube formation of HUVEC,which is related to the down-regulation of HIF1α/Ang1 signal axis.


Assuntos
Artrite Experimental/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Glicosídeos/farmacologia , Tripterygium/química , Inibidores da Angiogênese/farmacologia , Angiotensina I/metabolismo , Animais , Artrite Experimental/induzido quimicamente , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Membrana Sinovial/efeitos dos fármacos , Comprimidos , Fator A de Crescimento do Endotélio Vascular
18.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3478-3485, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602912

RESUMO

Tripterygium Glycosides Tablets has good anti-inflammatory and immunomodulatory activities,but its reproductive damage is significant. Previous studies of the research group have found that Cuscutae Semen flavonoids can improve spermatogenic cell damage caused by Tripterygium Glycosides Tablets by regulating spermatogenic cell cycle,apoptosis and related protein expression,but the mechanism of action at the gene level is still unclear. In this study,Illumina high-throughput sequencing platform was applied in transcriptional sequencing of spermatogenic cells of rats after the intervention of Cuscutae Semen flavonoids and Tripterygium Glycosides Tablets. Differentially expressed genes were screened out and the GO enrichment and KEGG pathway analysis of differentially expressed genes were conducted to explore the mechanism of Cuscutae Semen flavonoids in improving reproductive injury caused by Tripterygium Glycosides Tablets. The results showed that 794 up-regulated genes and 491 down-regulated genes were screened in Tripterygium Glycosides Tablets group compared with the blank group. Compared with Tripterygium Glycosides Tablets,440 up-regulated genes and 784 down-regulated genes were screened in the Cuscutae Semen flavonoids+Tripterygium Glycosides Tablets group. Among them,the gene closely related to reproductive function is DNMT3 L. Analysis of GO function and KEGG signaling pathway enrichment showed that the above differentially expressed genes were mainly enriched in cell,cell process,catalytic activity,binding,ovarian steroid synthesis,thyroid hormone and other functions and pathways. The thyroid hormone signaling pathway was the common enrichment pathway of the two control groups. In a word,Cuscutae Semen flavonoids has a good treatment effect on male reproductive damage caused by Tripterygium Glycosides Tablets. The mechanism may be closely related to up-regulation of DNMT3 L genes and intervention of thyroid hormone signaling pathway. At the same time,the discovery of many different genes provides valuable information for study on the mechanism of Cuscutae Semen flavonoids and Tripterygium Glycosides Tablets compatibility decreasing toxicity and increasing efficiency.


Assuntos
Cuscuta/química , Flavonoides/farmacologia , Genitália/efeitos dos fármacos , Glicosídeos/toxicidade , Tripterygium/toxicidade , Animais , DNA (Citosina-5-)-Metiltransferases/genética , Feminino , Genitália/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Masculino , Ratos , Sementes/química , Transdução de Sinais , Comprimidos , Hormônios Tireóideos/genética , Transcriptoma
19.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3486-3493, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602913

RESUMO

The aim of this paper was to observe the toxic effect of Tripterygium Glycosides Tablets( TG) on the reproductive system of Ⅱ type collagen induced arthritis( CIA) male rats,and to explore the toxic mechanism preliminarily. Fifty SD rats were randomly divided into normal control group( Con),model group( CIA),Tripterygium Glycosides Tablets clinical equivalent dose groups of 1,2,4 times( 9,18,36 mg·kg-1),10 rats in each group,and were given by gavage once a day for 42 days after the first immunization.The organ indexes of uterine and ovarian were calculated on days 21 and 42. Histopathological and morphological changes of uterine and ovarian were observed under optical microscope. The concentration of estradiol( E2),follicle-stimulating hormone( FSH),luteinizing hormone( LH),17α-hydroxylase( CYP17 A1) and cytochrome P450 19 A1( CYP19 A1) in serum were detected by ELISA. Immunohistochemistry was used to observe the expression of Bax and Bcl-2 related proteins in the apoptosis pathway of uterus and ovary. The results showed that compared with the Con group,CIA group could reduce the number of uterine glands( P<0.05),but no significant changes were observed in other groups. Compared with the CIA group,there were no significant changes in the coefficients of uterus and ovary in the Tripterygium Glycosides Tablets groups. The number of uterine glands,total follicles in the ovary,mature follicles and corpus luteum,the distribution of blood vessels and mitochondria had a certain inhibitory trend,and also slightly increased the number of atresia follicles,but the histopathological quantitative indicators were not statistically different. Except that 2 times clinical dose of Tripterygium Glycosides Tablets could significantly reduce the content of CYP19 A1( P<0. 05) after 42 d administration,there were no significant changes in serum estrogen E2,FSH,LH and estrogen synthesis key enzymes CYP17 A1 in each administration group. Medium and high doses of Tripterygium Glycosides Tablets could increase the expression of apoptotic protein Bax in uterine and ovarian tissues( P<0. 05,P<0. 01),and all the administration groups could inhibit the expression of apoptotic inhibiting protein Bcl-2( P <0. 05,P<0. 01,P<0.001),42 d was more obvious than 21 d. In conclusion,4 times and less than 4 times Tripterygium Glycosides Tablets did not cause obvious toxicity and histopathological changes in the reproductive organs of CIA rats,but it could reduce the level of serum estrogen synthesis key enzyme CYP19 A1 and affect the content of apoptosis-related proteins Bax and Bcl-2 in uterus and ovary tissues. The relevant mechanism needs further study.


Assuntos
Artrite Experimental/tratamento farmacológico , Medicamentos de Ervas Chinesas/toxicidade , Genitália Feminina/efeitos dos fármacos , Glicosídeos/toxicidade , Tripterygium/química , Animais , Apoptose , Aromatase/metabolismo , Artrite Experimental/induzido quimicamente , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Glicosídeos/farmacologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Comprimidos
20.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3494-3501, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602914

RESUMO

The aim of this paper was to compare the performance of acute liver injury in mice induced by Tripterygium Glycosides Tablets from 6 different manufacturers,and to explore the toxicity mechanism from the perspective of oxidative stress and apoptosis preliminarily. Male or female mice were randomly divided into normal group,Zhejiang group,Hunan group,Hubei group,Shanghai group,Jiangsu group and Fujian group. Mice in Tripgerygium Glycosides Tablets groups were given 16 times the clinical equivalent dose( 300 mg·kg-1) Tripgerygium Glycosides Tablets by oral administration for one time,mice were executed in 24 h after lavaged.Then the visceral brain coefficient of the organ was calculated. Histopathological changes of liver were observed by hematoxylin-eosin staining. Td T-mediated d UTP nick-end labeling was used to detect the apoptosis of the liver cells and the protein content of oxidative stress related factors in liver homogenate. Nuclear transcription factor E2-related factor( Nrf2) and heme oxygenase-1( HO-1) as well as mitochondrial mediated apoptosis-related protein expression levels of Bax and Bcl-2 in hepatic tissue were measured by Western blot.Within 24 hours of administration,6 male mice in Jiangsu group and 2 female mice in Zhejiang group were dying; compared with normal ones,liver coefficients of mice in Zhejiang,Shanghai,Jiangsu and Hunan groups were significantly increased,thymus coefficients in the first two groups were significantly reduced,as well as the lung coefficients of Fujian group mice,the rest was normal. In addition to Hubei group,serum AST,ALT or ALP levels of mice were increased,while TBi L were not being affected. Histopathological changes and apoptosis of liver cells were observed in all mice,and the degree of severity was ranked as Jiangsu,Zhejiang,Shanghai,Hunan,Hubei and Fujian group. All Tripterygium Glycosides Tablets increased the MDA and reduced the content of T-SOD,CAT or GSH in liver tissue while inhibited Nrf2,HO-1 and Bcl-2,increased the protein expression level of Bax( except Hunan group). Tripgerygium Glycosides Tablets from 6 manufacturers all resulted in liver function damage and liver histopathological changes,especially in Jiangsu,Hubei and Fujian,and the mechanism may related to inhibit Nrf2/HO-1 oxidative stress pathway and activate Bax/Bcl-2 apoptosis pathway to mediate lipid peroxidation and induce liver cell apoptosis. Triptolide A may be one of the main toxic components of Tripgerygium Glycosides Tablets that causing drug-induced liver injury. This study was conducted on normal mice with super dose medication,so the relevant results are for reference only.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas/toxicidade , Glicosídeos/toxicidade , Tripterygium/toxicidade , Animais , Apoptose , Feminino , Heme Oxigenase-1/metabolismo , Peroxidação de Lipídeos , Fígado/efeitos dos fármacos , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Distribuição Aleatória , Comprimidos , Proteína X Associada a bcl-2/metabolismo
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