RESUMO
Insufficient catalytic efficiency of flavonoid 6-hydroxylases in the fermentative production of scutellarin leads to the formation of at least about 18% of by-products. Here, the catalytic mechanisms of two flavonoid 6-hydroxylases, CYP82D4 and CYP706X, were investigated by molecular dynamics simulations and quantum chemical calculations. Our results show that CYP82D4 and CYP706X have almost identical energy barriers at the rate-determining step and thus similar reaction rates, while the relatively low substrate binding energy of CYP82D4 may facilitate product release, which is directly responsible for its higher catalytic efficiency. Based on the study of substrate entry and release processes, the catalytic efficiency of the L540A mutation of CYP82D4 increased by 1.37-fold, demonstrating the feasibility of theoretical calculations-guided engineering of flavonoid 6-hydroxylase. Overall, this study reveals the catalytic mechanism of flavonoid 6-hydroxylases, which may facilitate the modification and optimization of flavonoid 6-hydroxylases for efficient fermentative production of scutellarin.
Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Apigenina , GlucuronatosRESUMO
Drinking culture has high significance in both China and the world, whether in the entertainment sector or in social occasions; according to the World Health Organization's 2018 Global Alcohol and Health Report, about 3 million people died from excessive drinking in 2016, accounting for 5.3% of the total global deaths that year. Oxidative stress and inflammation are the most common pathological phenomena caused by alcohol abuse (Snyder et al., 2017). Scutellarin, a kind of flavonoid, is one of the main active ingredients extracted from breviscapine. It exerts anti-inflammatory, antioxidant, and vasodilation effects, and has been used to treat cardiovascular diseases and alcoholic liver injury. Although scutellarin can effectively alleviate multi-target organ injury induced by different forms of stimulation, its protective effect on alcoholic brain injury has not been well-defined. Therefore, the present study established an acute alcohol mice brain injury model to explore the effect of scutellarin on acute alcoholic brain injury. The study was carried out based on the targets of oxidative stress and inflammation, which is of great significance for the targeted therapy of clinical alcohol diseases.
Assuntos
Animais , Humanos , Camundongos , Apigenina/uso terapêutico , Lesões Encefálicas/tratamento farmacológico , Glucuronatos/uso terapêutico , Estresse OxidativoRESUMO
Oligosaccharides and dietary fibres are non-digestible food ingredients that preferentially stimulate the growth of prebiotic Bifidobacterium and other lactic acid bacteria in the gastro-intestinal tract. Xylooligosaccharides (XOS) provide a plethora of health benefits and can be incorporated into several functional foods. In the recent times, there has been an over emphasis on the microbial conversion of agroresidues into various value added products. Xylan, the major hemicellulosic component of lignocellulosic materials (LCMs), represents an important structural component of plant biomass in agricultural residues and could be a potent bioresource for XOS. On an industrial scale, XOS can be produced by chemical, enzymatic or chemo-enzymatic hydrolysis of LCMs. Chemical methods generate XOS with a broad degree of polymerization (DP), while enzymatic processes will be beneficial for the manufacture of food grade and pharmaceutically important XOS. Xylooligomers exert several health benefits, and therefore, have been considered to provide relief from several ailments. This review provides a brief on production, purification and structural characterization of XOS and their health benefits.
Assuntos
Adjuvantes Imunológicos/economia , Adjuvantes Imunológicos/isolamento & purificação , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/uso terapêutico , Animais , Anticarcinógenos/economia , Anticarcinógenos/isolamento & purificação , Anticarcinógenos/farmacologia , Anticarcinógenos/uso terapêutico , Antioxidantes/economia , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Biomassa , Sequência de Carboidratos , Cromatografia/métodos , Produtos Agrícolas/química , Produtos Agrícolas/economia , Fibras na Dieta/análise , Proteínas Fúngicas/metabolismo , Trato Gastrointestinal/microbiologia , Glucuronatos/economia , Glucuronatos/isolamento & purificação , Glucuronatos/farmacologia , Glucuronatos/uso terapêutico , Humanos , Hidrólise , Lignina/análise , Microbiota/efeitos dos fármacos , Dados de Sequência Molecular , Estrutura Molecular , Oligossacarídeos/economia , Oligossacarídeos/isolamento & purificação , Oligossacarídeos/farmacologia , Oligossacarídeos/uso terapêutico , Prebióticos/economia , Resíduos/economia , Xilanos/químicaRESUMO
Background & objectives: Alcohol misuse has now become a serious public health problem and early intervention is important in minimizing the harm. Biochemical markers of recent and high levels of alcohol consumption can play an important role in providing feedback regarding the health consequences of alcohol misuse. Existing markers are not sensitive to recent consumption and in detecting early relapse. Ethyl glucuronide (EtG), a phase-II metabolite of ethanol is a promising marker of recent alcohol use and can be detected in body fluids. In this study an analytical technique for quantitation of EtG in body fluids using solid-phase extraction (SPE) and gas chromatography (GC) with mass spectrometric detection (MS) was developed and validated. Methods: De-proteinization of serum and urine samples was done with perchloric acid and hydrochloric acid, respectively. Serum samples were passed through phospholipids removal cartridges for further clean up. EtG was isolated using amino propyl solid phase extraction columns. Chromatographic separation was achieved by gas chromatography with mass spectrometry. Results: Limit of detection and limit of quantitation were 50 and 150 ng/ml for urine and 80 and 210 ng/ml for serum, respectively. Signal to noise ratio was 3:1, mean absolute recovery was 80-85 per cent. Significant correlation was obtained between breath alcohol and serum EtG levels (r=0.853) and urine EtG and time since last abuse (r = -0.903) in clinical samples. Interpretation & conclusions: In the absence of other standardized techniques to quantitate EtG in biological samples, this gc -ms method was found to have high throughput and was sensitive and specific.
Assuntos
Transtornos Induzidos por Álcool , Cromatografia Gasosa-Espectrometria de Massas , Glucuronatos/análise , Glucuronatos/sangue , Glucuronatos/urina , Humanos , Extração em Fase SólidaRESUMO
Totally 80 rats were randomly divided into the control group, the model group, low, middle and high dose (25, 50, 100 mg x kg(-1)) scutellarin( SC) groups and the colchicine ( Col) group. Apart from the blank group, all of the remaining groups were intraperitoneally injected with 0.5 mL pig serum twice every week for consecutively 13 weeks and orally administered with the corresponding drugs since the 9th week. The blank group and the model group were orally given equal volume of normal saline once every for consecutively four weeks. After the experiment, efforts were made to detect the contents of alanine aminotransferase (ALT), aspertate aminotransferase (AST), albumin (ALB), total protein (TP), total bilirubin (TBIL), hyaluronic acid (HA), laminin (LN) and collagen type IV (CIV), collect liver tissues of fixed positions, observe the pathological changes through hematoxylin-eosin (HE) staining, conduct the pathological grading for liver fibrosis, determine the expressions of hepatic collagen type I and III (C I, C III) and calculate their color rendering index. Compared with the model group, low, middle and high dose (25, 50, 100 mg x kg(-1)) SC groups could decrease the contents of ALT, AST, TBIL, HA, LN, CIV, increase the contents of ALB, TP in serum and reduce the contents of C I, C III in liver tissues. In conclusion, scutellarin has a certain therapeutic effect on immune liver fibrosis in rats induced by pig serum.
Assuntos
Animais , Humanos , Masculino , Ratos , Alanina Transaminase , Genética , Metabolismo , Apigenina , Bilirrubina , Genética , Metabolismo , Colágeno Tipo IV , Genética , Metabolismo , Medicamentos de Ervas Chinesas , Glucuronatos , Fígado , Metabolismo , Cirrose Hepática , Tratamento Farmacológico , Genética , Metabolismo , Ratos Sprague-DawleyRESUMO
Scutellarin (SCU), a flavonoid from a traditional Chinese medicinal plant. Our previous study has demonstrated that SCU relaxes mouse aortic arteries mainly in an endothelium-depend-ent manner. In the present study, we investigated the vasoprotective effects of SCU against HR-induced endothelial dysfunction (ED) in isolated rat CA and the possible mechanisms involving cyclic guanosine monophosphate (cGMP) dependent protein kinase (PKG). The isolated endothelium-intact and endothelium-denuded rat CA rings were treated with HR injury. Evaluation of endothelium-dependent and -independent vasodilation relaxation of the CA rings were performed using wire myography and the protein expressions were assayed by Western blotting. SCU (10-1 000 μmol·L(-1)) could relax the endothelium-intact CA rings but not endothelium-denuded ones. In the intact CA rings, the PKG inhibitor, Rp-8-Br-cGMPS (PKGI-rp, 4 μmol·L(-1)), significantly blocked SCU (10-1 000 μmol·L(-1))-induced relaxation. The NO synthase (NOS) inhibitor, NO-nitro-L-arginine methylester (L-NAME, 100 μmol·L(-1)), did not significantly change the effects of SCU (10-1 000 μmol·L(-1)). HR treatment significantly impaired ACh-induced relaxation, which was reversed by pre-incubation with SCU (500 μmol·L(-1)), while HR treatment did not altered NTG-induced vasodilation. PKGI-rp (4 μmol·L(-1)) blocked the protective effects of SCU in HR-treated CA rings. Additionally, HR treatment reduced phosphorylated vasodilator-stimulated phosphoprotein (p-VASP, phosphorylated product of PKG), which was reversed by SCU pre-incubation, suggesting that SCU activated PKG phosphorylation against HR injury. SCU induces CA vasodilation in an endothelium-dependent manner to and repairs HR-induced impairment via activation of PKG signaling pathway.
Assuntos
Animais , Ratos , Apigenina , Farmacologia , Moléculas de Adesão Celular , Hipóxia Celular , Vasos Coronários , GMP Cíclico , Metabolismo , Farmacologia , Proteínas Quinases Dependentes de GMP Cíclico , Glucuronatos , Farmacologia , Proteínas dos Microfilamentos , NG-Nitroarginina Metil Éster , Metabolismo , Farmacologia , Fosfoproteínas , Ratos Sprague-Dawley , Traumatismo por Reperfusão , Transdução de Sinais , Tionucleotídeos , Metabolismo , Farmacologia , Vasodilatação , FisiologiaRESUMO
Estudo descritivo cujos objetivos foram elaborar títulos diagnósticos de enfermagem segundo a CIPE®, realizar mapeamento cruzado entre as formulações diagnósticas e os títulos diagnósticos da NANDA-I, identificar dentre os títulos diagnósticos formulados os constantes e não constantes na NANDA-I e realizar mapeamento dos títulos formulados com as Necessidades Humanas Básicas. Utilizou-se técnica de oficina, com 32 enfermeiros de unidades de terapia intensiva, de mapeamento cruzado e de validação por concordância com peritos. Na oficina foram elaborados 1.665 títulos diagnósticos submetidos a processo de refinamento que resultou em 120 títulos, submetidos a mapeamento cruzado com títulos diagnósticos da NANDA-I e com as necessidades humanas básicas. Os produtos do mapeamento foram submetidos à validação de conteúdo por dois enfermeiros peritos, obtendo-se índices de concordância de 92% e 100%. Constatou-se que 63 títulos constavam na NANDA-I e 47 não.
This descriptive study aimed at elaborating nursing diagnostic labels according to ICNP®; conducting a cross-mapping between the diagnostic formulations and the diagnostic labels of NANDA-I; identifying the diagnostic labels thus obtained that were also listed in the NANDA-I; and mapping them according to Basic Human Needs. The workshop technique was applied to 32 intensive care nurses, the cross-mapping and validation based on agreement with experts. The workshop produced 1665 diagnostic labels which were further refined into 120 labels. They were then submitted to a cross-mapping process with both NANDA-I diagnostic labels and the Basic Human Needs. The mapping results underwent content validation by two expert nurses leading to concordance rates of 92% and 100%. It was found that 63 labels were listed in NANDA-I and 47 were not.
Estudio descriptivo cuyos objetivos fueron la elaboración de etiquetas de diagnósticos de enfermería según la CIPE®, para llevar a cabo lo mapeo cruzado entre el diagnóstico formulado y las etiquetas de los diagnósticos NANDA-I, para identificar entre los títulos de diagnósticos formulados los que eran constantes y no constantes en NANDA-I y asignarlos a las necesidades humanas básicas. Fueron conducidas técnica de oficina con 32 enfermeros de las unidades de cuidados intensivos, mapeo cruzado y validación de acuerdo con los expertos. Se elaboró 1665 títulos diagnósticos en la oficina sometidos a un proceso de refinamiento. El resultado fue de 120 títulos que se presentaron a un proceso de mapeo con los títulos de diagnósticos de la NANDA-I y con las necesidades humanas básicas. Validación de contenido se realizó con los productos de lo mapeo por dos enfermeras expertas y las tasas de concordancia del 92% y 100% fueron obtenidas. Se encontró que 63 títulos estaban contenidos en la NANDA-I y 47 no lo hicieron.
Assuntos
Animais , Masculino , Ratos , Malonatos/metabolismo , Microssomos Hepáticos/metabolismo , Tolueno/análogos & derivados , Fenômenos Químicos , Química , Relação Dose-Resposta a Droga , Cromatografia Gasosa-Espectrometria de Massas , Glucuronatos/metabolismo , Injeções Intravenosas , Microssomos Hepáticos/efeitos dos fármacos , Ratos Endogâmicos , Tolueno/administração & dosagem , Tolueno/metabolismo , XenobióticosRESUMO
OBJECTIVE: to investigate the burnout syndrome and its relationship with demographic and academic variables among undergraduate nursing students at a public university in Southern Brazil. METHOD: a quantitative study with 168 students, by applying an adaptation of the Maslach Burnout Inventory - Student Survey, validated for this study. We used descriptive and variance analysis of the data analysis. RESULTS: we found that students do not have the burnout syndrome, manifesting high average scores in Emotional Exhaustion, low in Disbelief and high in Professional Effectiveness; that younger students who perform leisure activities have greater Professional Effectiveness, unlike students in early grades with no extracurricular activities; combining work and studies negatively influenced only the Professional Effectiveness factor, while the intention of giving up influenced negatively Disbelief and Professional Effectiveness factors. CONCLUSION: the situations that lead students to Emotional Exhaustion need to be recognized, considering the specificity of their study environments. .
OBJETIVO: investigar a síndrome de Burnout e sua relação com variáveis sociodemográficas e acadêmicas, entre estudantes de graduação em enfermagem de uma universidade pública do Sul do Brasil. MÉTODO: estudo quantitativo, realizado com 168 estudantes, mediante a aplicação de uma adaptação do Maslach Burnout Inventory - Student Survey, validada para este estudo. Utilizou-se a análise descritiva e de variância para análise dos dados. RESULTADOS: constatou-se que os estudantes não apresentam a síndrome de Burnout, manifestando médias altas em exaustão emocional, baixas em descrença e altas em eficácia profissional; que estudantes mais jovens e que realizam atividades de lazer apresentam maior eficácia profissional, diferentemente de estudantes das séries iniciais e que não realizam atividades extracurriculares; conciliar trabalho e estudos influenciou negativamente apenas o fator eficácia profissional, enquanto a intenção de desistir do curso influenciou negativamente os fatores descrença e eficácia profissional. CONCLUSÃO: faz-se necessário o reconhecimento das situações que levam os estudantes à exaustão emocional, considerando a especificidade de seus ambientes de formação. .
OBJETIVO: investigar la síndrome de burnout y su relación con variables sociodemográficas y académicas, entre estudiantes de pregrado en enfermería de una universidad pública del Sur de Brasil. MÉTODO: estudio cuantitativo, desarrollado con 168 estudiantes, mediante la aplicación de una adaptación del Maslach Burnout Inventory - Student Survey, validada para fines de ese estudio. Fueron utilizados los análisis descriptivo y de variancia para analizar los datos. RESULTADOS: se constató que los estudiantes no presentan la síndrome de burnout, manifestando altos promedios en Agotamiento Emocional, bajos en Descreencia y altos en Eficacia Profesional; que estudiantes más jóvenes y que practican actividades de ocio presentan mayor Eficacia Profesional, diferentemente de estudiantes de los años iniciales sin actividades extracurriculares; conciliar trabajo y estudios influyó negativamente apenas el factor Eficacia Profesional, mientras la intención de desistir del curso influyó negativamente los factores Descreencia y Eficacia Profesional. CONCLUSIÓN: es necesario reconocer las situaciones que llevan a los estudiantes al Agotamiento Emocional, considerando la especificidad de sus ambientes de formación. .
Assuntos
Animais , Masculino , Ratos , Cromatografia Líquida de Alta Pressão/métodos , Glucuronatos/análise , Malonatos/metabolismo , Microssomos Hepáticos/análise , Sulfetos/análise , Glucuronatos/metabolismo , Glucuronosiltransferase/metabolismo , Microssomos Hepáticos/metabolismo , Ratos Endogâmicos , Compostos de Sulfidrila/metabolismo , Sulfetos/metabolismoRESUMO
Evidence-based medicine is advocated by WHO and adopted by developed countries for many years. In China, however, the selection of essential medicine and various medical insurance reimbursement schemes medicine is usually based on experts' experience of prescription practice which is under heavy critics resulting from the lack of related comparative efficacy and evidence-based research. The efficacy of Jian'ganle in prevention of drug-induced liver injury (DILI) caused by antituberculotics was evaluated in this study by comparison with Hugan Pian, glucuronolactone and reduced glutathione. Evidence was provided for relevant sectors such as Ministry for Human Resources and Social Security of the People's Republic of China and National Health and Family Planning Commission of the People's Republic of China to select and renew the Essential Medicine List (EML), the new rural cooperative medical scheme in China (NRCMS) list or the reimbursement list of industrial injury insurance. A total of 189 patients with initial pulmonary tuberculosis were divided into four groups who took antituberculotics combined with Jian'ganle, Hugan Pian, glucuronolactone and reduced glutathione respectively. Their liver function profile including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), total protein (TP), albumin (A) and globulin (G) were detected at admission as baseline and after treatment. The Jian'ganle group was compared with the three others by chi-square tests. In an aspect of maintaining bilirubin indexes normal, Jian'ganle was more efficacious than glucuronolactone. And Jian'ganle had a little more efficacy than reduced glutathione to maintain protein indexes normal as well. And the therapeutic regimen of antituberculotics combined with Jian'ganle was the best in treating tuberculosis and preventing DILI at the same time. The study showed that among the four hepatinicas which demonstrated similar prevention of DILI caused by antituberculotics, Jian'ganle has more advantages over the three others to some extent, which provides a reliable basis for health sectors to select and renew the EML, NRCMS List or the reimbursement list of industrial injury insurance.
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Alanina Transaminase , Metabolismo , Antituberculosos , Usos Terapêuticos , Povo Asiático , Aspartato Aminotransferases , Metabolismo , Bilirrubina , Doença Hepática Induzida por Substâncias e Drogas , China , Medicina Baseada em Evidências , Glucuronatos , Usos Terapêuticos , Glutationa , Usos Terapêuticos , Fígado , Patologia , Testes de Função Hepática , Medicina Tradicional Chinesa , Resultado do Tratamento , Tuberculose Pulmonar , Tratamento Farmacológico , EtnologiaRESUMO
Scutellarin is the main effective constituent of breviscapine, a flavonoid mixture isolated from the dried whole plant of Erigeron breviscapus (Vant.) Hand-Mazz, and valsartan is used as an antihypertensive drug. These two drugs have already been clinically used together to treat diabetic nephropathy (DN) in China, and the combined medications showed some enhanced protection against DN. The aim of this study is to investigate the potential pharmacokinetic interaction between scutellarin and valsartan in rats. Breviscapine injection (20 mg x kg(-1), i.v.) and valsartan (15 mg x kg-, i.g.), either alone or together were given to 18 male Sprague-Dawley rats. Concentrations of scutellarin and valsartan were quantified by HPLC, and pharmacokinetic parameters were calculated by non-compartmental methods. We found that the pharmacokinetic parameters of scutellarin altered significantly after co-administration of oral valsartan. The plasma clearance (CL(p)) and the bile clearance (CL(b)) of scutellarin were reduced significantly in the presence of valsartan. After oral administration of valsartan with or without intravenous scutellarin, however, the pharmacokinetic parameters of valsartan were comparable. In conclusion, our data suggests that the concurrent use of valsartan reduces the biliary excretion of scutellarin, and this may be due to the inhibitory effect of valsartan on the biliary excretion of scutellarin mediated by Mrp2 (Multidrug resistance-associated protein 2).
Assuntos
Animais , Masculino , Ratos , Administração Intravenosa , Administração Oral , Anti-Hipertensivos , Sangue , Farmacocinética , Apigenina , Sangue , Farmacocinética , Bile , Metabolismo , Cromatografia Líquida de Alta Pressão , Interações Medicamentosas , Erigeron , Química , Glucuronatos , Sangue , Farmacocinética , Taxa de Depuração Metabólica , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Metabolismo , Plantas Medicinais , Química , Distribuição Aleatória , Ratos Sprague-Dawley , Valsartana , Sangue , FarmacocinéticaRESUMO
<p><b>OBJECTIVE</b>Scutellarin from Erigeron breviscapus is a flavonoid with remarkable pharmacological activity, whose route of biosynthesis is still fully clear. Chalcone synthase (CHS) is the key enzyme regulating flavonoids biosynthesis, and the aim of this study is to explain the relationship between patterns of the gene expression and scutellarin content through studying CHS gene expression patterns combined with scutellarin content in various parts of E. breviscapus.</p><p><b>METHOD</b>Through RT-PCR and RACE, the full length of CHS was cloned and analyzed by fluorescent quantitative PCR. The scutellarin content in tissues was analyzed by HPLC.</p><p><b>RESULT</b>The full-length gene sequence was 1 270 bp, encoding 405 amino acids. Software analysis found that the DNA sequence was 80% similarity with Compositae plant homeo-box gene. Fluorescence quantitative analysis showed that CHS had the highest expression level in leaves, far higher than that in root, stem and flower. HPLC analysis showed that the scutellarin was the highest in leaves, followed by the flowers and stems, scutellarin was not detected in root.</p><p><b>CONCLUSION</b>Correlation analysis showed that CHS expression amount and scutellarin content in different parts of E. breviscapus is positive correlation (r = 0.761, P < 0.05), it suggests that CHS gene expression level has important effect on biosynthesis of scutellarin.</p>
Assuntos
Aciltransferases , Genética , Metabolismo , Sequência de Aminoácidos , Apigenina , Genética , Metabolismo , Erigeron , Genética , Metabolismo , Expressão Gênica , Genes de Plantas , Glucuronatos , Genética , Metabolismo , Medicina Tradicional Chinesa , Dados de Sequência Molecular , Plantas Medicinais , Genética , MetabolismoRESUMO
<p><b>OBJECTIVE</b>A high-performance liquid chromatographic (HPLC) method was developed for simultaneous determination of chlorogenic acid, scutellarin, 3,5-dicaffeoylquinic acid, 4,5-dicaffeoylquinic acid in different parts of Erigerontis Herba.</p><p><b>METHOD</b>The four constituents were measured on an Agilent Zorbax SB-C18 column (4.6 mm x 450 mm, 5 microm) with a gradient elution of acetonitrile (A) -0.3% phosphoric acid solution (B) (0-10 min, 12%-15% A, 10-32 min, 15% A, 32-33 min, 15%-20% A, 33-50 min, 20%-22% A) at wavelength of 335 nm and 327 nm, and a flow rate of 1.0 mL x min(-1) and the column temperature was 30 degrees C.</p><p><b>RESULT</b>Linearity of each standard was established in the concentration range of 0.050 1-1.002 microg for chlorogenic acid, 0.165 9-3.318 microg for chlorogenic acid, 0.049 7-0.994 microg for 3,5-dicaffeoylquinic acid, 0.048 7-0.974 p.g for 4,5-dicaffeoylquinic acid respectively, with correlation coefficient r > 0.999 6. Average recoveries (n = 6) of 4 compounds were 98.53% with a RSD of 0.94%, 99.68% with a RSD of 0.49%, 98.78% with a RSD of 1.1%, 99.06% with a RSD of 0.81%, respectively.</p><p><b>CONCLUSION</b>The developed method is simple, accurate, and precise, it can be used for the quantitative analysis of Erigeron breviscapus.</p>
Assuntos
Apigenina , Química , Ácido Clorogênico , Química , Cromatografia Líquida de Alta Pressão , Métodos , Medicamentos de Ervas Chinesas , Química , Erigeron , Química , Glucuronatos , Química , Ácido Quínico , QuímicaRESUMO
To develop a HPLC method for determination of the concentration of scutellarin and scutellarin ethyl ester and their pharmacokinetics were also compared. 104 mg kg-1of scutellarin or 114. 5 mg kg-1 scutellarin ethyl ester were given at single dose by oral gavarge. Blood samples were collected from the jugular vein. Plasma concentration was measured by HPLC. The pharmacokinetic parameters were calculated with Winnonlin program. The plasma concentration-time profile of scutellarin and scutellarin ethyl ester were both fitted with non-compartment model and both were double peaks. The main pharmacokinetic parameters of scutellarin and scutellarin ethyl ester were as follows: Tmax Cmax and AUC0-t for scutellarin were (6 +/- 1.26) h, (321.55 +/-48.31) microg L-1 and (2 974 +/-753) h micro.g L-1; for scutellarin ethyl ester, Tmax, Cmax and AUC0-t were 0.5 h, (1 550.82 +/-219.75) +/- microg L- and (6 407 +/- 399) h microg L-1. The speed ingested into the blood of scutellarin ethyl ester was faster than scutellarin, and the bioavailability of scutellarin ethyl ester was two times higher than scutellarin.
Assuntos
Animais , Masculino , Ratos , Apigenina , Farmacocinética , Cromatografia Líquida de Alta Pressão , Flavonas , Farmacocinética , Glucuronatos , Farmacocinética , Glucuronídeos , Farmacocinética , Ratos WistarRESUMO
<p><b>OBJECTIVE</b>To prepare the new traditional Chinese medicine preparation--pH-dependent brevisapin colon-specific tablets, and investigate its in vitro release, in order to discuss the feasibility of preparing colon-targeted traditional Chinese medicines.</p><p><b>METHOD</b>With scutellarin, the active ingredient in brevisapin, as the evaluation index, coating prescriptions of the preparation was screened. The in vitro release determination method was adopted to detect the in vitro release performance of the preparation.</p><p><b>RESULT</b>The in vitro release determination results showed no brevisapin in artificial pH 1. 2 dilute hydrochloric acid solution for 2 h, an accumulated dissolution rate of less than 5% in pH 6. 8 phosphate buffer solution for 4 h, but an accumulated dissolution rate exceeding 90% in pH 7. 6 phosphate buffer solution for 1 h.</p><p><b>CONCLUSION</b>Brevisapin colon-specific tablets prepared can realize colon-specific release.</p>
Assuntos
Administração Oral , Apigenina , Química , Soluções Tampão , Química Farmacêutica , Métodos , Colo , Medicamentos de Ervas Chinesas , Química , Glucuronatos , Química , Ácido Clorídrico , Química , Concentração de Íons de Hidrogênio , Especificidade de Órgãos , Solubilidade , ComprimidosRESUMO
<p><b>OBJECTIVE</b>To establish a UPLC-MS/MS analysical method for simultaneous determination of concentrations of isoorientin, scutellarin and cynaroside in rat plasma and to study their pharmacokinetic characteristics after intravenous injection of 3 doses of Fufang Hongcao in rats.</p><p><b>METHOD</b>Acidified plasma samples were precipitated for protein with methanol. Waters Acquity BEH C18 column was adopted for spectrum, with mobile phase as 0. 1% formic acid acetonitrile-0. 1% formic acid-water gradient elution. Detection was carried out by the multiple reaction monitoring (MRM) positive ion mode with ESI ionization source.</p><p><b>RESULT</b>Three flavonoids show a good linear relationship, with the extraction recovery ranging between 78.56% and 101.91% and a high intra-and inter-day precisions and accuracy. The MRT of the three flavonoids were all lower than 22 min in rats.</p><p><b>CONCLUSION</b>The above men tioned method is so specific, rapid, sensitive that it is suitable for pharmacokinetic studies of Fufang Hongcao injection in rats.</p>
Assuntos
Animais , Feminino , Masculino , Ratos , Apigenina , Sangue , Farmacocinética , Cromatografia Líquida de Alta Pressão , Métodos , Medicamentos de Ervas Chinesas , Farmacocinética , Glucosídeos , Sangue , Farmacocinética , Glucuronatos , Sangue , Farmacocinética , Luteolina , Sangue , Farmacocinética , Espectrometria de Massas em Tandem , Métodos , Fatores de TempoRESUMO
<p><b>OBJECTIVE</b>To study scutellarin starch microspheres' permeability through nasal mucosa of different animals in vitro.</p><p><b>METHOD</b>The Franz diffusion cell method was used to experiment the permeability test (n = 4), taking fresh nasal mucosa of dog, swine and domestica in vitro as permeation barrier separately, with scutellarin starch microspheres (scutellarin 0.25 mg) above them, and blank pH 6.8 PBS as absorption liquid to detemine the scutellarin by HPLC.</p><p><b>RESULT</b>The permeability coefficient of scutellarin starch microspheres through nasal mucosa of dog, swine and domestica in vitro were (5.295 +/- 0.637) x 10(-3) (4.065 +/- 1.140) x 10(-3), (1.855 +/- 0.150) x 10(-3) cm x mL(-1) separately. The permeability coefficient order of scutellarin starch microspheres through nasal mucosa of different animals in vitro is dog > swine > domestica, and there are significant differences between the permeability coefficient of scutellarin starch microspheres through nasal mucosa of dog, swine in vitro, and that through nasal mucosa of swine and domestica in vitro.</p><p><b>CONCLUSION</b>Drugs in scutellarin starch microspheres could permeate through the above-mentioned nasal mucosa in vitro. There might be different permeability coefficient among different species.</p>
Assuntos
Animais , Cães , Apigenina , Farmacocinética , Glucuronatos , Farmacocinética , Microesferas , Mucosa Nasal , Metabolismo , Permeabilidade , Amido , Farmacocinética , Suínos , Porco MiniaturaRESUMO
This paper aims to establish a new method of calibration and positioning in quantitative analysis of multicomponents by single marker (QAMS), using Shuanghuanglian oral liquid as the research object. Establishing relative correction factors with reference chlorogenic acid to other 11 active components (neochlorogenic acid, cryptochlorogenic acid, cafferic acid, forsythoside A, scutellarin, isochlorogenic acid B, isochlorogenic acid A, isochlorogenic acid C, baicalin and phillyrin wogonoside) in Shuanghuanglian oral liquid by 3 correction methods (multipoint correction, slope correction and quantitative factor correction). At the same time chromatographic peak was positioned by linear regression method. Only one standard uas used to determine the content of 12 components in Shuanghuanglian oral liquid, in stead of needing too many reference substance in quality control. The results showed that within the linear ranges, no significant differences were found in the quantitative results of 12 active constituents in 3 batches of Shuanghuanglian oral liquid determined by 3 correction methods and external standard method (ESM) or standard curve method (SCM). And this method is simpler and quicker than literature methods. The results were accurate and reliable, and had good reproducibility. While the positioning chromatographic peaks by linear regression method was more accurate than relative retention time in literature. The slope and the quantitative factor correction controlling the quality of Chinese traditional medicine is feasible and accurate.
Assuntos
Apigenina , Calibragem , Ácido Clorogênico , Cromatografia Líquida de Alta Pressão , Métodos , Medicamentos de Ervas Chinesas , Química , Flavanonas , Flavonoides , Glucosídeos , Glucuronatos , Glicosídeos , Reprodutibilidade dos TestesRESUMO
To study the chemical constituents of Trichosanthes kirilowii Maxim., chromatographic methods such as D101 macroporous resin, silica gel column chromatographic technology, Sephadex LH-20, octadecylsilyl (ODS) column chromatographic technique and preparative HPLC were used and nine compounds were isolated from a 95% (v/v) ethanol extract of the plant. By using spectroscopic techniques including 1H NMR, 13C NMR, 1H-1H COSY, HSQC and HMBC, these compounds were identified as 5-ethoxymethyl-1-carboxyl propyl-1H-pyrrole-2-carbaldehyde (1), 5-hydroxymethyl-2-furfural (2), chrysoeriol (3), 4'-hydroxyscutellarin (4), vanillic acid (5), alpha-spinasterol (6), beta-D-glucopyranosyl-a-spinasterol (7), stigmast-7-en-3beta-ol (8), and adenosine (9), separately. Among them, compound 1 is a new compound, and compounds 3, 4 and 5 are isolated from the genus Trichosanthes kirilowii Maxim. for the first time.
Assuntos
Apigenina , Química , Flavonas , Química , Frutas , Química , Glucuronatos , Química , Estrutura Molecular , Plantas Medicinais , Química , Pirróis , Química , Trichosanthes , Química , Ácido Vanílico , QuímicaRESUMO
Scutellarin is a flavonoid extracted from a traditional Chinese herb, Erigeron breviscapus. The present study investigated the effect of scutellarin on MUC5AC mucin production and the possible mechanism. Human bronchial epithelial 16 (HBE16) cells were pretreated with scutellarin for 60 min, and then exposed to human neutrophil elastase (HNE) or interleukin (IL)-13 for 12 hr. RT-PCR and ELISA were performed to measure the amount of MUC5AC mucin production. The results showed that scutellarin inhibited MUC5AC expression both in mRNA and protein level induced by HNE in a concentration-dependent manner. However, scutellarin failed to inhibit MUC5AC mucin production induced by IL-13. To investigate the intracellular mechanisms associated with the effect of scutellarin on MUC5AC mucin production, western blotting was carried out to examine the phosphorylation of protein kinase C (PKC), signal transducer and activator of transcription 6 (STAT6) and extracellular signal-regulated kinase 1/2 (ERK1/2). The phosphorylation of PKC and ERK1/2 was attenuated after treatment with scutellarin, whereas STAT6 was not significantly affected. Therefore, it is suggested that scutellarin down-regulates MUC5AC mucin production on HBE16 cells via ERK-dependent and PKC-dependent pathways.
Assuntos
Humanos , Apigenina/química , Células Cultivadas , Relação Dose-Resposta a Droga , Regulação para Baixo , Células Epiteliais/efeitos dos fármacos , Erigeron/química , Glucuronatos/química , Interleucina-13/farmacologia , Elastase de Leucócito/farmacologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Mucina-5AC/genética , Fosforilação , Proteína Quinase C/metabolismo , Mucosa Respiratória/efeitos dos fármacos , Fator de Transcrição STAT6/metabolismo , Transdução de SinaisRESUMO
This study is to investigate the transportation of scutellarin in cell and live models and study on mechanism of absorption and transport of scutellarin in mouse liver. The concentration of scutellarin in plasma and liver from control and pretreated groups was determined by high performance liquid chromatography. The uptake of scutellarin was examined in control hepatocytes group, induced hepatocytes group and induced hepatocytes plus pravastatin group. Pravastatin can affect the pharmacokinetics of scutellarin in mouse: CL is decreased while AUC is increased. The scutellarin absorption of hepatocyte induced group was higher than that of control group, but was decreased in the group with pravastatin added. The research showed that there was potential drug interaction between pravastatin and scutellarin. The drugs may compete for oatp2 mediated transport pathway consisted in the uptake of scutellarin in liver.