RESUMO
This article is to explore the antidepressant mechanism of Shugan Lipi recipe in regulating tryptophan metabolism,and to find out their common pharmacodynamic substances. UPLC-Q-TOF-MS technology was used to establish fingerprints of Shugan Lipi recipe,and 124 components were identified. The depressed mouse model was replicated by triple-one multiple stress method. Chaihu Shugan Powder,Sini Powder and Xiaoyao Powder were administered in groups to observe the changes in body weight and behavior of the mice. The results showed that compared with the model group,the body weight,sucrose preference percentage and autonomous activity behavior of each administration group were improved. Among them,the effect of Chaihu Shugan Powder was better than that of Sini Powder and Xiaoyao Powder. LC-MS/MS method was used to determine the contents of 5-hydroxytryptamine( 5-HT),kynurenine( KYN) and tryptophan( TPP) in blood,liver,brain,colon and other tissues,as well as TDO enzyme activity in liver. Western blot and RT-PCR were used to detect the protein and gene expression of TDO enzyme,respectively. It was found that the three prescriptions increased the ratio of 5-HT/KYN in different degrees,decreased the ratio of KYN/TRP in liver,colon and brain,and decreased the expression level and activity of TDO enzyme in liver. The order of their ability to regulate tryptophan metabolism was Chaihu Shugan Powder>Sini Powder>Xiaoyao Powder. In addition,the correlation between the chromatographic peaks in the fingerprints of Shugan Lipi recipes and the pharmacodynamic indexes of tryptophan metabolism was analyzed by the grey relation analysis. The grey relation analysis found that the chemical components with the highest correlation with tryptophan metabolism were mainly from Paeoniae Radix Alba,Citri Reticulatae Pericarpium,Aurantii Fructus Immaturus and Aurantii Fructus. UPLC-Q-TOF-MS was used to analyze the migration components in the plasma of mice after administration of Shugan Lipi recipe,and to verify the common pharmacodynamic substances of Shugan Lipi recipe. The migration of these detected components in plasma was studied,and a total of 18 prototype components and 36 metabolites were identified. Therefore,it was believed that Chaihu Shugan Powder,Sini Powder and Xiaoyao Powder could play an antidepressant role by reducing the expression of TDO enzyme in the liver and regulating the metabolism of tryptophan.The components contained in Paeoniae Radix Alba,Citri Reticulatae Pericarpium,Aurantii Fructus Immaturus and Aurantii Fructus were the common pharmacodynamic substances of Shugan Lipi recipe,which played an important role in regulating tryptophan metabolism.
Assuntos
Paeonia , Triptofano , Animais , Antidepressivos , Cromatografia Líquida , Camundongos , Espectrometria de Massas em TandemRESUMO
In this study, an acidic polysaccharide from Codonopsis pilosula Nannf. var. modesta (Nannf.) L. T. Shen (WCP-I) and its main fragment, WCP-Ia, obtained after pectinase digestion, were structurally elucidated and found to consist of a rhamnogalacturonan I (RG-I) region containing both arabinogalactan type I (AG-I) and type II (AG-II) as sidechains. They both expressed immunomodulating activity against Peyer's patch cells. Endo-1,4-ß-galactanase degradation gave a decrease of interleukine 6 (IL-6) production compared with native WCP-I and WCP-Ia, but exo-α-l-arabinofuranosidase digestion showed no changes in activity. This demonstrated that the stimulation activity partly disappeared with removal of ß-d-(1â4)-galactan chains, proving that the AG-I side chain plays an important role in immunoregulation activity. WCP-Ia had a better promotion effect than WCP-I in vivo, shown through an increased spleen index, higher concentrations of IL-6, transforming growth factor-ß (TGF-ß), and tumor necrosis factor-α (TNF-α) in serum, and a slight increment in the secretory immunoglobulin A (sIgA) and CD4+/CD8+ T lymphocyte ratio. These results suggest that ß-d-(1â4)-galactan-containing chains in WCP-I play an essential role in the expression of immunomodulating activity. Combining all the results in this and previous studies, the intestinal immune system might be the target site of WCP-Ia.
Assuntos
Codonopsis/química , Fatores Imunológicos/farmacologia , Imunomodulação/efeitos dos fármacos , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Hidrólise , Imunidade nas Mucosas/efeitos dos fármacos , Fatores Imunológicos/química , Camundongos , Estrutura Molecular , Monossacarídeos/química , Nódulos Linfáticos Agregados/efeitos dos fármacos , Nódulos Linfáticos Agregados/imunologia , Nódulos Linfáticos Agregados/metabolismo , Extratos Vegetais/química , Polissacarídeos/química , Análise EspectralRESUMO
The success of all-trans retinoic acid (ATRA) in differentiation therapy for patients with acute promyelocytic leukemia (APL) highly encourages researches to apply a new combination therapy based on ATRA. Therefore, research strategies to further sensitize cells to retinoids are urgently needed. In this study, we showed that Dihydromyricetin (DMY), a 2,3-dihydroflavonol compound, exhibited a strong synergy with ATRA to promote APL NB4 cell differentiation. We observed that DMY sensitized the NB4 cells to ATRA-induced cell growth inhibition, CD11b expression, NBT reduction and myeloid regulator expression. PML-RARα might not be essential for DMY-enhanced differentiation when combined with ATRA, while the enhanced differentiation was dependent on the activation of p38-STAT1 signaling pathway. Taken together, our study is the first to evaluate the synergy of DMY and ATRA in NB4 cell differentiation and to assess new opportunities for the combination of DMY and ATRA as a promising approach for future differentiation therapy.
Assuntos
Flavonóis/administração & dosagem , Leucemia Promielocítica Aguda/tratamento farmacológico , Fator de Transcrição STAT1/metabolismo , Tretinoína/administração & dosagem , Antineoplásicos/administração & dosagem , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sinergismo Farmacológico , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Leucemia Promielocítica Aguda/metabolismo , Leucemia Promielocítica Aguda/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas de Fusão Oncogênica/metabolismo , Proteólise/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
Based on previous studies about microflora regulation and immunity enhancement activities of polysaccharides from Codonopsis pilosula Nannf. var. modesta (Nannf.) L. T. Shen (CPP), there is little study on intestinal mucosal immunity, which is a possible medium for contacting microflora and immunity. In the present study, the BALB/c mice were divided into five groups (eight mice in each group), including a normal group (Con), a model control group (Model), and model groups that were administered CPP (50, 100, 200 mg/kg/d) orally each day for seven days after intraperitoneal injection of 60 mg/kg BW/d cyclophosphamide (CP) for three days. CPP recovered the spleen index and restored the levels of IFN-γ, IL-2, IL-10, as well as serum IgG. In addition, it elevated ileum secretory immunoglobulin A (sIgA), the number of Lactobacillus and acetic acid content in cecum. These results indicated that CPP plays an important role in the protection against immunosuppression, especially mucosa immune damage, and the inhibition of pathogenic bacteria colonization, which could be considered a potential natural source of immunoregulator.
Assuntos
Codonopsis/química , Ciclofosfamida/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Imunidade/efeitos dos fármacos , Hospedeiro Imunocomprometido , Fatores Imunológicos/farmacologia , Imunossupressores/farmacologia , Polissacarídeos/farmacologia , Animais , Citocinas/sangue , Imunidade nas Mucosas/efeitos dos fármacos , Imunoglobulina A Secretora/sangue , Imunoglobulina A Secretora/imunologia , Fígado/efeitos dos fármacos , Fígado/imunologia , Camundongos , Baço/efeitos dos fármacos , Baço/imunologia , Timo/efeitos dos fármacos , Timo/imunologiaRESUMO
Soil microorganisms are important components of terrestrial ecosystems, affecting soil formation and fertility, plant growth and stress tolerance, nutrient turnover and carbon storage. In this study, we collected soil samples (humus layer, 0-10 cm, 10-20 cm, 20-40 cm, and 40-80 cm) from Caragana jubata shrubland in Shanxi subalpine to explore the composition, diversity, and assembly of soil bacterial communities at different depths across the soil profile. The results showed that Actinomycota (19%-28%), Chloromycota (10%-36%) and Acidobacteria (15%-24%), and Proteobacteria (9%-25%) were the dominant bacterial phyla. α-diversity of soil bacterial community significantly decreased with the increases of soil depth. Soil bacterial ß-diversity varied across different soil depths. Soil pH, water content, and enzyme activity were the main ecological factors affecting the distribution of soil bacterial communities. Soil bacterial communities had more complex interactions in humus layer and 0-10 cm layer. On the whole, soil bacterial communities were dominated by coexistence in C. jubata shrubland, and the soil bacterial community assembly was driven by random process.
Assuntos
Caragana , Solo , Solo/química , Ecossistema , Microbiologia do Solo , Bactérias , ChinaRESUMO
The roots of Salvia miltiorrhiza have been used in Traditional Chinese Medicine for thousands of years. However, tons of aerial parts of this plant are usually discarded in the production of roots preparation. To make better use of these plant resources, the polysaccharide isolated from the aerial part of S. miltiorrhiza was investigated for its potential protection against intestinal diseases. A pectic polysaccharide (SMAP-1) was isolated and characterized being composed of homogalacturonan as the main chain and rhamnogalacturonan type I as ramified region, with side chains including arabinans and possible arabinogalactan type I and II. SMAP-1 exhibited robust protective effects against dextran sodium sulfate (DSS)-induced colitis and restored colitis symptoms, colonic inflammation, and barrier functions. Anti-oxidative effects were also observed by up-regulating Nrf2/Keap1 signaling pathway. Additionally, the level of serum 5-methoxyindole-3-carboxaldehyde (5-MC) was restored by SMAP-1 identified in metabolomic analysis, being correlated with the aforementioned effects. Protection against oxidative stress on intestinal porcine enterocyte cells (IPEC-J2) by 5-MC was observed through the activation of Nrf2/Keap1 system, as also shown by SMAP-1. In conclusion, SMAP-1 could be a promising candidate for colitis prevention, and 5-MC could be the signal metabolite of SMAP-1 in protecting against oxidative stress in the intestine.
Assuntos
Colite , Salvia miltiorrhiza , Animais , Suínos , Fator 2 Relacionado a NF-E2/metabolismo , Salvia miltiorrhiza/química , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Transdução de Sinais , Polissacarídeos/efeitos adversos , Sulfato de Dextrana/toxicidadeRESUMO
This study examined the application of slim-hole nuclear magnetic resonance (NMR) tools to estimate hydraulic conductivity (KNMR ) in an unconsolidated aquifer that contains a range of grain sizes (silt to gravel) and high and variable magnetic susceptibilities (MS) (10-4 to 10-2 SI). A K calibration dataset was acquired at 1-m intervals in three fully screened wells, and compared to KNMR estimates using the Schlumberger-Doll research (SDR) equation with published empirical constants developed from previous studies in unconsolidated sediments. While KNMR using published constants was within an order of magnitude of K, the agreement, overprediction, or underprediction of KNMR varied with the MS distribution in each well. An examination of the effects of MS on NMR data and site-specific empirical constants indicated that the exponent on T2ML (n-value in the SDR equation, representing the diffusion regime) was found to have the greatest influence on KNMR estimation accuracy, while NMR porosity did not improve the prediction of K. KNMR was further improved by integrating an MS log into the NMR analyses. A first approach detrended T2ML for the effects of MS prior to calculating KNMR , and a second approach introduced an MS term into the SDR equation. Both were found to produce similar refinements of KNMR in intervals of elevated MS. This study found that low frequency NMR logging with short echo times shows promise for sites with moderate to elevated MS levels, and recommends a workflow that examines parameter relationships and integrates MS logs into the estimation of KNMR .
Assuntos
Água Subterrânea , Movimentos da Água , Calibragem , Água Subterrânea/análise , Espectroscopia de Ressonância Magnética , PorosidadeRESUMO
One purified neutral polysaccharide fraction was obtained from the rhizome of Polygonatum sibiricum by DEAE ion exchange and gel chromatography. Structure elucidation was performed by methanolysis, methylation, FT-IR, and NMR. The results indicated that PSP-NP was composed of 1,4-ß-D-Gal,1, 4, 6-ß-D-Gal, T-α-D-Man,1, 4-α-D-Glc, and T-α-D-Glc with a molecular weight of 43.0 kDa. We supplied this polysaccharide to aged mice and found it is of benefits to intestinal functions, as indicated by better tissue integrity and motility, improved oxidative stress and inflammation, reduced intestinal permeability and serum LPS level, as well as balanced gut microbial composition and short-chain fatty acids production. These results display a novel Polygonatum sibiricum polysaccharide to improve the intestinal function of aged mice, which provides pieces of evidence for its further development and utilization.
RESUMO
Eighteen schizandrin A derivatives, possessing an acyl group at 7-OH and/or halogen(s) at C-4 and C-11, were designed and synthesized for evaluation of their in vitro ability to inhibit multidrug resistance (MDR). They exhibit weak ability to restore the intracellular Rhodamine 123 in human hepatocarcinoma MDR cell lines Bel7402 and HCT8 relative to the reference drug verapamil.
Assuntos
Ciclo-Octanos/síntese química , Ciclo-Octanos/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Lignanas/síntese química , Lignanas/farmacologia , Compostos Policíclicos/síntese química , Compostos Policíclicos/farmacologia , Ciclo-Octanos/química , Humanos , Lignanas/química , Estrutura Molecular , Compostos Policíclicos/química , Rodamina 123/análise , Schisandra/química , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: Percutaneous transluminal balloon angioplasty (PTA) is recommended as the first choice to treat stenosis of Brescia-Cimino arteriovenous fistulas (B-C AVFs). The ability to predict which B-C AVFs are at risk for recurrent stenosis post-PTA would allow closer monitoring of patients, and possibly result in surgical intervention rather than repeat PTA. The purpose of this study was to identify predictive factors of primary patency after PTA in B-C AVFs. METHODS: Patients diagnosed with B-C AVF primary stenosis and treated by PTA between November 2013 and March 2018 were included in the study. Patient and stenotic lesion characteristics and PTA procedure factors were included in the analysis. The Kaplan-Meier method was used to analyze the primary patency rate. Cox proportional hazard regression analysis was used to identify factors predictive of decreased primary patency. RESULTS: 74 patients (35 males, 39 females) with a mean age of 61.68 ± 11.44 years (range, 36-84 years) were included in the study. The mean B-C AVF age was 16.34 ± 12.93 months (range, 2-84 months), and the median primary patency time was 7.79 ± 0.48 months. Cox proportional hazard regression analysis revealed stenosis location at the inflow artery [hazard ratio (HR)=3.83, 95% confidence interval (CI): 1.46-10.09] or anastomosis (HR = 1.90, 95% CI: 1.09-3.32), dilation >2 times during PTA (HR = 2.30, 95% CI: 1.22-4.34), and residual stenosis >30% (HR = 2.42, 95% CI: 1.26-4.63) were significantly associated with decreased patency. CONCLUSION: In conclusion, the primary patency rate of PTA for B-C AVF dysfunction is reduced by dilation >2 times, residual stenosis >30%, and stenosis located at the inflow artery or anastomosis. These results may help in tailoring surveillance programs, multiple PTA, or a proximal re-anastomosis surgery in patients with AVF dysfunction. ADVANCES IN KNOWLEDGE: A number of studies have been conducted to examine the predictors of primary patency after PTA, however, no definitive conclusions have been reached. Our study revealed that stenosis location at the inflow artery or anastomosis, dilation >2 times during PTA, and residual stenosis >30% were the predictors of primary patency after PTA, which may help in tailoring surveillance programs, multiple PTA, or a proximal re-anastomosis surgery in patients with arteriovenous fistulas dysfunction.
Assuntos
Angioplastia com Balão/métodos , Derivação Arteriovenosa Cirúrgica , Oclusão de Enxerto Vascular/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Constrição Patológica/terapia , Procedimentos Endovasculares/métodos , Falha de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Renal/instrumentação , Resultado do Tratamento , Grau de Desobstrução Vascular/fisiologiaRESUMO
Two polysaccharides, MDP-1 and MDP-2, were obtained from the fermentation liquid of M. dendrobii by anion exchange chromatography and gel filtration. Their chemical structures were measured by FT-IR, GC, 1H and 13C NMR spectra, indicating the mainly compositions of mannose, xylose, and galactose for MDP-1; galacturonic acid, galactose and rhamnose for MDP-2. Furthermore, the antioxidant activities of MDPs were investigated, showing different antioxidant activities, in which MDP-2 performed noticeable, with excellent superoxide radical activity better than BHT, high DPPH radical activity (IC50 at 227 µg/mL) comparable with BHT, moderate reducing power activity and hydroxyl radical scavenging activity. The results indicated that the fermentation liquid of M. dendrobii could be used as a potential natural source of antioxidant.
Assuntos
Agaricales/química , Sequestradores de Radicais Livres/química , Polissacarídeos/química , Compostos de Bifenilo/química , Sequestradores de Radicais Livres/isolamento & purificação , Hexoses/química , Radical Hidroxila/química , Picratos/química , Polissacarídeos/isolamento & purificação , Superóxidos/químicaRESUMO
RsmA is an RNA-binding protein functioning as a global post-transcriptional regulator of various cellular processes in bacteria and has been demonstrated to be an important virulence regulator in many animal bacterial pathogens. However, its function in other phytopathogenic bacteria is unclear, except for the Erwinia carotovora RsmA, which acts as a negative virulence regulator. In this work, we investigated the function of the rsmA-like gene, named rsmA(Xcc), of the phytopathogen Xanthomonas campestris pv. campestris. Deletion of rsmA(Xcc) resulted in complete loss of virulence on the host plant Chinese radish, hypersensitive response on the nonhost plant pepper ECW-10R, and motility on the surface of an agar plate. The rsmA(Xcc) mutant displayed a significant reduction in the production of extracellular amylase, endoglucanase, and polysaccharide, but a significant increase in intracellular glycogen accumulation and an enhanced bacterial aggregation and cell adhesion. Microarray hybridization and semiquantitative reverse-transcription polymerase chain reaction analysis showed that deletion of rsmA(Xcc) led to significantly reduced expression of genes encoding the type III secretion system (T3SS), T3SS-effectors, and the bacterial aggregate dispersing enzyme endo-beta-1,4-mannanase. These results suggest that rsmA(Xcc) is involved in the control of various cellular processes, including pathogenesis of X. campestris pv. campestris.
Assuntos
Proteínas de Bactérias/genética , Regulação Bacteriana da Expressão Gênica , Mutação , Xanthomonas campestris/genética , Sequência de Aminoácidos , Amilases/metabolismo , Proteínas de Bactérias/fisiologia , Celulase/metabolismo , Glicogênio/metabolismo , Modelos Genéticos , Dados de Sequência Molecular , Análise de Sequência com Séries de Oligonucleotídeos , Polissacarídeos/metabolismo , Raphanus/crescimento & desenvolvimento , Raphanus/microbiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência de Aminoácidos , Virulência/genética , Xanthomonas campestris/metabolismo , Xanthomonas campestris/patogenicidadeRESUMO
The ColR-ColS two-component signal transduction system was originally characterized as a regulatory system involved in the capacity of root-colonizing biocontrol bacterium Pseudomonas fluorescens to colonize plant roots. There are three pairs of putative colR-colS two-component regulatory systems annotated in the phytopathogen Xanthomonas campestris pathovar campestris. Mutational studies revealed that one of them, named colR(XC1049) and colS(XC1050), is a global regulatory system involved in various cellular processes, including virulence, hypersensitive response and stress tolerance. Growth rate determination showed that, although the colR(XC1049) and colS(XC1050) mutants are not auxotrophic, colR(XC1049) and colS(XC1050) are required for the pathogen to proliferate well in standard media and host plants. Assays of beta-glucuronidase activities of plasmid-driven promoter-gusA reporters and/or semi-quantitative RT-PCR demonstrated that colR(XC1049) and colS(XC1050) positively regulate expression of hrpC and hrpE operons, and that expression of colR(XC1049) and colS(XC1050) is not controlled by key hrp regulators HrpG and HrpX.
Assuntos
Proteínas de Bactérias/metabolismo , Óperon , Doenças das Plantas/microbiologia , Raphanus/microbiologia , Transdução de Sinais , Regulação para Cima , Xanthomonas campestris/patogenicidade , Proteínas de Bactérias/genética , Regulação Bacteriana da Expressão Gênica , Mutação , Virulência , Xanthomonas campestris/genética , Xanthomonas campestris/fisiologiaRESUMO
To collect the researching documents of recent years about the pharmacodynamics research and modem clinic application of Huangqintang and its relative prescription, and to discuss the current general situation of the pharmacodynamics research and clinic application. Huangqintang has the pharmacodynamics effect such as resist bacteria and inflammation, adjust immune system, ease pain, protect the liver, lower the index of aminotransferase, anti-cancer and virus, lower the physical temperature, and calm down the emotion. The original and relative prescription can be commonly used in curing intestines disease such as diarrhea, acute enteritis and gastritis, ameba diarrhea, etc. It can also be used in internal medicine, gynecology, dermatology, etc.
Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , HumanosRESUMO
In the present investigation, we carried a phytochemical study of an ethanol-soluble extract from the root barks of Aspidistra typica Baill., a traditional food and herb medicine, leading to the isolation of four different kinds of compounds, including one benzene substituted coumarin, two organic phosphonic compounds, and one xanthone. The novel benzene substituted coumarin typicacoumarin A (1) was a new type of coumarin, and the two new organic phosphonic compounds, typicalphosphine A (2) and typicalphosphine B (3) were isolated for the first time, and their structures were elucidated by spectral techniques, viz.1D, 2D NMR spectra and HR-ESI-MS. The xanthone compound typicaxanthone A (4) was discovered from nature for the first time. The two new organic phosphonic chlorides (2, 3) showed stronger antibacterial activities, which were comparable to berberine hydrochloride. And typicaxanthone A (4) showed much stronger antibacterial activity against Escherichia coli ATCC-25922 bacterial strain, while typicacoumarin A (1) showed moderate antibacterial activities, weaker than berberine hydrochloride.
Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Liliaceae/química , Antibacterianos/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Raízes de Plantas/química , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
Highly dynamic mitotic spindle microtubules are superb therapeutic targets for a group of chemically diverse and clinically successful anticancer drugs. Microtubule-targeted drugs disrupt microtubule dynamics in distinct ways, and they are primarily classified into two groups: microtubule destabilizing agents (MDAs), such as vinblastine, colchicine, and combretastatin-A4, and microtubule stabilizing agents (MSAs), such as paclitaxel and epothilones. Systematic discovery and development of new MSAs have been aided by extensive research on paclitaxel, yielding a large number of promising anticancer compounds. This review focuses on the natural sources, structural features, mechanisms of action, structure-activity relationship (SAR) and chemical synthesis of MSAs. These MSAs mainly include paclitaxel, taccalonolides, epothilones, FR182877 (cyclostreptin), dictyostatin, discodermolide, eleutherobin and sarcodictyins, zampanolide, dactylolide, laulimalides, peloruside and ceratamines from natural sources, as well as small molecular microtubule stabilizers obtained via chemical synthesis. Then we discuss the application prospect and development of these anticancer compounds.
Assuntos
Antineoplásicos/farmacologia , Produtos Biológicos/farmacologia , Microtúbulos/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , Animais , Antineoplásicos/química , Produtos Biológicos/química , Relação Dose-Resposta a Droga , Humanos , Microtúbulos/metabolismo , Estrutura Molecular , Bibliotecas de Moléculas Pequenas/química , Relação Estrutura-AtividadeRESUMO
To discuss the present general situation of the pharmacodynamics research of Guizhi decoction. Look up the literature about the research of pharmacodynamics experiments of Guizhi decoction in recent years, then to analyze and coordinate the useful information. Guizhi decoction has the bilateral accommodation for testing animals'suboriferous, body temperature, blood pressure, peristalsis and immune function. And it has the pharmacodynamics effect in resisting bacteria, virus, pain and allergy, reducing the blood sugar, increasing the cardiac muscle blood flux, improving the digestion and transmition of stomach and intestines, and easing up spasmus. It can also prevent the arthritis, and cure the cervical spondylosis and chronic pancreatitis.
Assuntos
Analgésicos/farmacologia , Antibacterianos/farmacologia , Antivirais/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Plantas Medicinais/química , Analgésicos/isolamento & purificação , Animais , Antibacterianos/isolamento & purificação , Antivirais/isolamento & purificação , Pressão Sanguínea/efeitos dos fármacos , Temperatura Corporal/efeitos dos fármacos , Medicamentos de Ervas Chinesas/isolamento & purificação , Humanos , Sudorese/efeitos dos fármacosRESUMO
Previously, 3,5-dipentadecyloxybenzamidine hydrochloride (TRX-20)-modified liposomes were reported to specifically target mesangial cells (MCs) in glomeruli. To further gain a better understanding of the characteristics and potential application for glomerular diseases of TRX-20-modified liposomes, we synthesized TRX-20 and prepared TRX-20-modified liposomes (TRX-LPs) with different molar ratios - 6% (6%-TRX-LP), 11% (11%-TRX-LP), and 14% (14%-TRX-LP) - of TRX-20 to total lipid in the present study. All TRX-LPs exhibited concentration-dependent toxicity against the MCs at a lipid concentration ranging from 0.01 to 1.0 mg/mL with IC50 values of 3.45, 1.13, and 0.55 mg/mL, respectively. Comparison of the cell viability of TRX-LPs indicated that high levels of TRX-20 caused severe cell mortality, with 11%-TRX-LP showing the higher cytoplasmic accumulation in the MCs. Triptolide (TP) as a model drug was first loaded into 11%-TRX-LP and the liposomes were further modified with PEG5000 (PEG-TRX-TP-LP) in an attempt to prolong their circulation in blood and enhance TP-mediated immune suppression. Due to specific binding to MCs, PEG-TRX-TP-LP undoubtedly showed better anti-inflammatory action in vitro, evidenced by the inhibition of release of nitric oxide (NO) and tumor necrosis factor-α from lipopolysaccharide-stimulated MCs, compared with free TP at the same dose. In vivo, the PEG-TRX-TP-LP effectively attenuated the symptoms of membranous nephropathic (MN) rats and improved biochemical markers including proteinuria, serum cholesterol, and albumin. Therefore, it can be concluded that the TRX-modified liposome is an effective platform to target the delivery of TP to glomeruli for the treatment of MN.
Assuntos
Diterpenos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Rim/efeitos dos fármacos , Lipossomos/administração & dosagem , Lipossomos/química , Fenantrenos/administração & dosagem , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Benzamidinas/química , Células Cultivadas , Diterpenos/química , Diterpenos/farmacologia , Compostos de Epóxi/administração & dosagem , Compostos de Epóxi/química , Compostos de Epóxi/farmacologia , Ácidos Graxos/química , Glomerulonefrite Membranosa/tratamento farmacológico , Rim/metabolismo , Masculino , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/metabolismo , Óxido Nítrico/metabolismo , Fenantrenos/química , Fenantrenos/farmacologia , Polietilenoglicóis/química , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Chinese patent medicines play an important role in veterinary clinical use. The aim of this study is to research the anti-infection effect of Chinese patent medicine "Wuhuanghu" for the treatment of porcine infectious pleuropneumonia and to evaluate the safety of "Wuhuanghu" in order to provide a comprehensive understanding of its toxicity. The anti-infection results showed that the treatment with "Wuhuanghu" could significantly inhibit pneumonia and decrement of the pneumonia in high, medium and low doses of "Wuhuanghu" groups were 70.97%, 61.29% and 58.06% respectively. The acute toxicity test showed that rats in the highest group (5000mg/kg) had no death and no abnormal response, suggesting the LD50 of "Wuhuanghu" was more than 5000mg/kg. The subchronic toxicity study showed that hematology indexes in all groups had no obvious differences; blood biochemical index, only albumin and total cholesterol in middle and low doses of "Wuhuanghu" groups were significantly decreased when compared with control group. The clinical pathology showed that the target organ of "Wuhuanghu" was liver. The safety pharmacology study indicated that "Wuhuanghu" had no side effects on rats. In conclusion, "Wuhuanghu" has therapeutic and protective effects to porcine infectious pleuropneumonia in a dose-dependent manner and "Wuhuanghu" is a safe veterinary medicine.
Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos sem Prescrição/administração & dosagem , Pleuropneumonia/veterinária , Doenças dos Suínos/tratamento farmacológico , Animais , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Fígado/efeitos dos fármacos , Masculino , Medicamentos sem Prescrição/efeitos adversos , Pleuropneumonia/tratamento farmacológico , Pleuropneumonia/patologia , Ratos , Suínos , Doenças dos Suínos/patologia , Testes de Toxicidade Aguda , Testes de Toxicidade Subcrônica , Drogas Veterinárias/administração & dosagem , Drogas Veterinárias/efeitos adversosRESUMO
The effects of acute and subacute toxicity of 1,8-cineole in Kunming mice were studied. After acute oral administration, the LD50 value (95% CL) was 3849 mg/kg (3488.8~4247.1 mg/kg). In the subacute toxicity study, there were no significant differences in body weight and relative organ weight between the control group and 1,8-cineole treatment groups. The histopathological examinations showed that granular degeneration and vacuolar degeneration appeared in liver and kidney tissue after administration of high dose of 1,8-cineole. Under electron microscopy, a series of ultrastructural changes were observed: The electron microscopy assays indicated that the influence of 1,8-cineole on the target organ at the subcellular level were mainly on the mitochondria, endoplasmic reticulum and other membrane type structure of liver and kidney.