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1.
Acta Pharmacol Sin ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31911638

RESUMO

Geissoschizine methyl ether (GM) is an indole alkaloid isolated from Uncaria rhynchophyll (UR) that has been used for the treatment of epilepsy in traditional Chinese medicine. An early study in a glutamate-induced mouse seizure model demonstrated that GM was one of the active ingredients of UR. In this study, electrophysiological technique was used to explore the mechanism underlying the antiepileptic activity of GM. We first showed that GM (1-30 µmol/L) dose-dependently suppressed the spontaneous firing and prolonged the action potential duration in cultured mouse and rat hippocampal neurons. Given the pivotal roles of ion channels in regulating neuronal excitability, we then examined the effects of GM on both voltage-gated and ligand-gated channels in rat hippocampal neurons. We found that GM is an inhibitor of multiple neuronal channels: GM potently inhibited the voltage-gated sodium (NaV), calcium (CaV), and delayed rectifier potassium (IK) currents, and the ligand-gated nicotinic acetylcholine (nACh) currents with IC50 values in the range of 1.3-13.3 µmol/L. In contrast, GM had little effect on the voltage-gated transient outward potassium currents (IA) and four types of ligand-gated channels (γ-amino butyric acid (GABA), N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainite (AMPA/KA receptors)). The in vivo antiepileptic activity of GM was validated in two electricity-induced seizure models. In the maximal electroshock (MES)-induced mouse seizure model, oral administration of GM (50-100 mg/kg) dose-dependently suppressed generalized tonic-clonic seizures. In 6-Hz-induced mouse seizure model, oral administration of GM (100 mg/kg) reduced treatment-resistant seizures. Thus, we conclude that GM is a promising antiepileptic candidate that inhibits multiple neuronal channels.

2.
Mar Drugs ; 16(11)2018 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-30380702

RESUMO

Alotamide is a cyclic depsipetide isolated from a marine cyanobacterium and possesses a unique activation of calcium influx in murine cerebrocortical neurons (EC50 4.18 µM). Due to its limited source, the three stereocenters (C19, C28, and C30) in its polyketide fragment remain undetermined. In this study, the first asymmetric synthesis of its polyketide fragment was achieved. Four relative possible diastereomers were constructed with a boron-mediated enantioselective aldol reaction and Julia⁻Kocienski olefination as the key steps. Comparison of 13C NMR spectra revealed the relative structure of fragment C15⁻C32 of alotamide.


Assuntos
Organismos Aquáticos/química , Cianobactérias/química , Depsipeptídeos/química , Policetídeos/química , Boro/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Policetídeos/síntese química , Estereoisomerismo
3.
Acta Pharmacol Sin ; 39(12): 1923-1934, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29795136

RESUMO

Timosaponin A3, a saponin in Zhimu, elicited hepatotoxicity via oxidative stress. However, the clinical medication of Zhimu has been historically regarded as safe, probably associated with the antioxidants it contains. However, the related information on the in vivo levels of timosaponin A3 and antioxidants remained unclear on Zhimu treatments. Therefore, a combination of the in vitro metabolism, including microbiota-mediated and liver-mediated metabolism, and in vivo pharmacokinetics and hepatic disposition, was conducted for three xanthones (neomangiferin, mangiferin, and norathyriol) and three saponins (timosaponin B2, timosaponin B3, and timosaponin A3) on Zhimu treatments. Consequently, following oral administration of Zhimu decoction to rats, those saponins and xanthones were all observed in the plasma with severe liver first-pass effect, where mangiferin was of the maximum exposure. Despite the ignorable content in the herb, timosaponin A3 elicited sizable hepatic exposure as the microbiota-mediated metabolite of saponins in Zhimu. The similar phenomenon also occurred to norathyriol, the microbiota-mediated metabolite of xanthones. However, the major prototypes in Zhimu were of limited hepatic exposure. We deduced the hepatic collection of norathyriol, maximum circulating levels of mangiferin, and timosaponin B2 and mangiferin interaction may directly or indirectly contribute to the whole anti-oxidation of Zhimu, and then resisted the timosaponin A3-induced hepatotoxicity. Thus, our study exploratively interpreted the discrepancy between herbal safety and timosaponin A3-induced hepatotoxicity. However, given the considerable levels and slow eliminated rate of timosaponin A3 in the liver, more attention should be paid to the safety on the continuous clinical medication of Zhimu in the future.


Assuntos
Antioxidantes/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Medicamentos de Ervas Chinesas/efeitos adversos , Saponinas/metabolismo , Esteroides/efeitos adversos , Xantonas/metabolismo , Administração Oral , Animais , Antioxidantes/farmacocinética , Asparagaceae/química , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/farmacocinética , Fígado/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Saponinas/efeitos adversos , Saponinas/farmacocinética , Esteroides/metabolismo , Esteroides/farmacocinética , Espectrometria de Massas em Tandem/métodos , Xantonas/farmacocinética
4.
BMC Pediatr ; 18(1): 110, 2018 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-29534692

RESUMO

BACKGROUND: Mandatory newborn screening for metabolic disorders has not been implemented in most parts of China. Newborn mortality and morbidity could be markedly reduced by early diagnosis and treatment of inborn errors of metabolism (IEM). Methods of screening for IEM by tandem mass spectrometry (MS/MS) have been developed, and their advantages include rapid testing, high sensitivity, high specificity, high throughput, and low sample volume (a single dried blood spot). METHODS: Dried blood spots of 100,077 newborns obtained from Jining city in 2014-2015 were screened by MS/MS. The screening results were further confirmed by clinical symptoms and biochemical analysis in combination with the detection of neonatal deficiency in organic acid, amino acid, or fatty acid metabolism and DNA analysis. RESULTS: The percentages of males and females among the 100,077 infants were 54.1% and 45.9%, respectively. Cut-off values were established by utilizing the percentile method. The screening results showed that 98,764 newborns were healthy, and 56 out of the 1313 newborns with suspected IEM were ultimately diagnosed with IEM. Among these 56 newborns, 19 (1:5267) had amino acid metabolism disorders, 26 (1:3849) had organic acid metabolism disorders, and 11 (1:9098) had fatty acid oxidation disorders. In addition, 54 patients with IEM were found to carry mutations, and the other 2 patients had argininemia. CONCLUSIONS: Fifty-six cases of metabolic disorders in Jining were confirmed via newborn screening (NBS) by MS/MS. Early diagnosis and treatment are crucial for the survival and well-being of affected children. A nationwide NBS program using MS/MS is recommended, especially in poor areas of China.


Assuntos
Erros Inatos do Metabolismo/diagnóstico , Triagem Neonatal/métodos , China/epidemiologia , Teste em Amostras de Sangue Seco , Diagnóstico Precoce , Feminino , Humanos , Incidência , Recém-Nascido , Masculino , Erros Inatos do Metabolismo/epidemiologia , Erros Inatos do Metabolismo/terapia , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem
5.
Acta Pharmacol Sin ; 37(2): 166-76, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26687936

RESUMO

AIM: N-methyl-D-aspartic acid (NMDA) receptor modulators have shown promising results as potential antidepressant agents, whereas timosaponins extracted from the Chinese herb Rhizoma Anemarrhenae exhibit antidepressant activities. In the present study we examined whether YY-23, a modified metabolite of timosaponin B-III, could affect NMDA receptors in rat hippocampal neurons in vitro, and evaluated its antidepressant-like effects in stressed mice. METHODS: NMDA-induced currents were recorded in acutely dissociated rat hippocampal CA1 neurons using a whole-cell recording technique. C57BL/6 mice were exposed to a 6-week chronic mild stress (CMS) or a 10-d chronic social defeat stress (CSDS). The stressed mice were treated with YY-23 (20 mg·kg(-1)·d(-1)) or a positive-control drug, fluoxetine (10 mg·kg(-1)·d(-1)) for 3 weeks. Behavioral assessments were carried out every week. RESULTS: In acutely dissociated rat hippocampal CA1 neurons, YY-23 selectively and reversibly inhibited NMDA-induced currents with an EC50 value of 2.8 µmol/L. This inhibition of NMDA-induced currents by YY-23 was non-competitive, and had no features of voltage-dependency or use-dependency. Treatment of the stressed mice with YY-23 not only reversed CMS-induced deficiency of sucrose preference and immobility time, and CSDS-induced reduction of social interaction, but also had faster onset as compared to fluoxetine. CONCLUSION: YY-23 is a novel non-competitive antagonist of NMDA receptors with promising rapid antidepressant-like effects in mouse models of CMS and CSDS depression.


Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Saponinas/uso terapêutico , Esteroides/uso terapêutico , Animais , Antidepressivos/química , Antidepressivos/metabolismo , Células Cultivadas , Depressão/metabolismo , Depressão/fisiopatologia , Hipocampo/citologia , Hipocampo/fisiopatologia , Magnésio/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/patologia , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/metabolismo , Saponinas/química , Saponinas/metabolismo , Esteroides/química , Esteroides/metabolismo , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo , Estresse Psicológico/fisiopatologia
6.
Xenobiotica ; 45(12): 1138-46, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26068524

RESUMO

1. The purpose of this study was to investigate the mechanism of hepatic uptake of berberine. Berberine accumulation in hepatocytes was found to be highly dependent on active uptake, which could not be explained by liver organic cation transporter (OCT) alone. 2. Our studies indicated that berberine uptake was significantly suppressed by rifampicin, cyclosporine A and glycyrrhizic acid, which act as specific inhibitors of different Oatp isoforms (Oatp1a1, Oatp1a4 and Oatp1b2) in rat hepatocytes. The combination of OCT and OATP inhibitors further reduced berberine accumulation in both rat and human hepatocytes. The uptake of berberine could be increased in human HEK293-OATP1B3 but not in OATP1B1-transfected HEK 293 cells. 3. Rifampicin could reduce the berberine liver extraction ratio (ER) and double its concentration in the effluent in isolated rat livers. Further in vivo study indicated that berberine plasma exposure could be significantly increased by co-administration of the OATP inhibitor rifampicin or the substrate rosuvastatin. 4. In conclusion, this study demonstrated that both OCT and OATP contribute to the accumulation of berberine in the liver. OATPs may have important roles in berberine liver disposition and potential clinically relevant drug--drug interactions.


Assuntos
Berberina/farmacocinética , Fígado/metabolismo , Transportadores de Ânions Orgânicos/metabolismo , Animais , Expressão Gênica/efeitos dos fármacos , Células HEK293 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Técnicas In Vitro , Fígado/efeitos dos fármacos , Masculino , Transportadores de Ânions Orgânicos/antagonistas & inibidores , Transportadores de Ânions Orgânicos/genética , Transportadores de Ânions Orgânicos Sódio-Independentes/antagonistas & inibidores , Transportadores de Ânions Orgânicos Sódio-Independentes/genética , Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismo , Cultura Primária de Células , Ratos , Ratos Sprague-Dawley , Rifampina/farmacologia , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto
7.
Acta Pharmacol Sin ; 35(9): 1188-98, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25087997

RESUMO

AIM: To investigate the mechanisms underlying the hepatotoxicity of timosaponin A3 (TA3), a steroidal saponin from Anemarrhena asphodeloides, in rats. METHODS: Male SD rats were administered TA3 (100 mg·kg(-1)·d(-1), po) for 14 d, and the blood and bile samples were collected after the final administration. The viability of a sandwich configuration of cultured rat hepatocytes (SCRHs) was assessed using WST-1. Accumulation and biliary excretion index (BEI) of d8-TCA in SCRHs were determined with LC-MS/MS. RT-PCR and Western blot were used to analyze the expression of relevant genes and proteins. ROS and ATP levels, and mitochondrial membrane potential (MMP) were measured. F-actin cytoskeletal integrity was assessed under confocal microscopy. RESULTS: TA3 administration in rats significantly elevated the total bile acid in serum, and decreased bile acid (BA) component concentrations in bile. TA3 inhibited the viability of the SCRHs with an IC50 value of 15.21±1.73 µmol/L. Treatment of the SCRHs with TA3 (1-10 µmol/L) for 2 and 24 h dose-dependently decreased the accumulation and BEI of d8-TCA. The TA3 treatment dose-dependently decreased the expression of BA transporters Ntcp, Bsep and Mrp2, and BA biosynthesis related Cyp7a1 in hepatocytes. Furthermore, the TA3 treatment dose-dependently increased ROS generation and HO-1 expression, decreased the ATP level and MMP, and disrupted F-actin in the SCRHs. NAC (5 mmol/L) significantly ameliorated TA3-induced effects in the SCRHs, whereas mangiferin (10-200 µg/mL) almost blocked TA3-induced ROS generation. CONCLUSION: TA3 triggers liver injury through inducing ROS generation and suppressing the expression of BA transporters. Mangiferin, an active component in Anemarrhena, may protect hepatocytes from TA3-induced hepatotoxicity.


Assuntos
Ácidos e Sais Biliares/metabolismo , Proteínas de Transporte/metabolismo , Regulação para Baixo/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Glicoproteínas de Membrana/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Saponinas/farmacologia , Esteroides/farmacologia , Animais , Células Cultivadas , Hepatócitos/metabolismo , Fígado/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley
8.
Nat Prod Res ; 28(18): 1446-53, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24749724

RESUMO

Timosaponin B-III (TB-III) is a steroidal saponin isolated from the rhizome of Anemarrhenae asphodeloides (Liliaceae). The biotransformation of TB-III by ß-glucosidase was investigated. Three biotransformation products were isolated and their structures were identified as timosaponin B-III-a (M1), (20R,25S)-5ß-spirostane-3ß-ol-3-O-ß-D-glucopyranosyl-(1 → 2)-ß-D-galacopyanoside (M2) and timosaponin AIII (M3). Then the four compounds were evaluated for their anti-depressive activity in mice by the open field test, tail suspension test and forced swimming test. As a result, TB-III, M1 and M3 exhibited modest anti-depressive activity. Structure-activity relationships were investigated and the preliminary conclusions are summarised as follows: the glycosyl at C-3 and C-26 can increase the activity, the double bond between C-20 and C-22 might be important for the anti-depressive activity, the R-configuration at C-22 and S-configuration at C-20 are necessary for its anti-depressive activity.


Assuntos
Antidepressivos/farmacologia , Liliaceae/química , Saponinas/farmacologia , Esteroides/farmacologia , Animais , Antidepressivos/química , Antidepressivos/isolamento & purificação , Biotransformação , Camundongos , Estrutura Molecular , Rizoma/química , Saponinas/química , Saponinas/isolamento & purificação , Esteroides/química , Esteroides/isolamento & purificação , Relação Estrutura-Atividade
9.
Planta Med ; 78(1): 18-23, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22002851

RESUMO

In the present study, the anti-diabetic effects of a traditional Chinese medicinal formula extract, TongGuanWan, were investigated in type 2 diabetic animals. It was orally administered to C57BL/KsJ-db/db mice once a day for 4 weeks at the doses of 62, 125, and 250 mg/kg body weight. TongGuanWan significantly lowered the blood glucose and glycosylated haemoglobin levels as well as improved the glucose tolerance in db/db mice. The serum triglyceride levels in the db/db mice were significantly decreased, whereas the high-density lipoprotein cholesterol levels were significantly increased, after treatment with this herbal formula. TongGuanWan also markedly decreased the animals' body weights compared to those of the control db/db group but did not alter food intake. The effects of TongGuanWan were compared to those of the drug rosiglitazone. In addition, five main constituents of TongGuanWan, mangiferin, berberine, cinnamic aldehyde, timosaponin BII, and timosaponin AIII, were quantified using high performance liquid chromatography coupled with a diode array and an evaporative light scattering detector (HPLC-DAD-ELSD). These results suggest that TongGuanWan may be useful for the treatment of type 2 diabetes.


Assuntos
Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Hemoglobina A Glicada/metabolismo , Hipoglicemiantes/uso terapêutico , Lipídeos/sangue , Acroleína/análogos & derivados , Acroleína/farmacologia , Acroleína/uso terapêutico , Administração Oral , Animais , Berberina/farmacologia , Berberina/uso terapêutico , HDL-Colesterol/sangue , Cromatografia Líquida de Alta Pressão , Diabetes Mellitus Tipo 2/sangue , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Intolerância à Glucose/sangue , Intolerância à Glucose/tratamento farmacológico , Hipoglicemiantes/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos Knockout , Fitoterapia , Rosiglitazona , Saponinas/farmacologia , Saponinas/uso terapêutico , Tiazolidinedionas/farmacologia , Triglicerídeos/sangue , Xantonas/farmacologia , Xantonas/uso terapêutico
10.
Molecules ; 16(5): 4264-77, 2011 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-21610656

RESUMO

The anti-HIV-1 activity of mangiferin was evaluated. Mangiferin can inhibit HIV-1(Ⅲ)(B) induced syncytium formation at non-cytotoxic concentrations, with a 50% effective concentration (EC50) at 16.90 µM and a therapeutic index (TI) above 140. Mangiferin also showed good activities in other laboratory-derived strains, clinically isolated strains and resistant HIV-1 strains. Mechanism studies revealed that mangiferin might inhibit the HIV-1 protease, but is still effective against HIV peptidic protease inhibitor resistant strains. A combination of docking and pharmacophore methods clarified possible binding modes of mangiferin in the HIV-1 protease. The pharmacophore model of mangiferin consists of two hydrogen bond donors and two hydrogen bond acceptors. Compared to pharmacophore features found in commercially available drugs, three pharmacophoric elements matched well and one novel pharmacophore element was observed. Moreover, molecular docking analysis demonstrated that the pharmacophoric elements play important roles in binding HIV-1 protease. Mangiferin is a novel nonpeptidic protease inhibitor with an original structure that represents an effective drug development strategy for combating drug resistance.


Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral/efeitos dos fármacos , Protease de HIV/metabolismo , HIV-1/efeitos dos fármacos , HIV-1/enzimologia , Xantonas/farmacologia , Fármacos Anti-HIV/química , Domínio Catalítico/efeitos dos fármacos , Linhagem Celular , Farmacorresistência Viral/genética , Protease de HIV/genética , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/virologia , Modelos Moleculares , Mutação/genética , Ligação Proteica/efeitos dos fármacos , Xantonas/química
11.
Zhonghua Er Ke Za Zhi ; 49(10): 765-70, 2011 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-22321184

RESUMO

OBJECTIVE: To determine the impact of expanded newborn screening using tandem mass spectrometry (MS/MS) on the overall detection rate of inborn errors of metabolism in Zhejiang province and to assess the outcome of the patients who were diagnosed. METHOD: Blood spots were collected between days 3 and 6 of life from the newborns. All samples were subjected to MS/MS analysis using Waters Quattro API. Confirmation tests included amino acid analysis, urinary organic acids by GC-MS, routine blood analysis, biochemistry, blood gas analysis, blood glucose and ammonia tests, blood homocysteine, lactate and pyruvate tests, urine acetone tests, biotin and biotin enzyme profile and DNA analysis. Standard treatment protocol was given to the patients. Protein restricted diet, special powdered formula and medicines recommended for the patients with amino acidemias. Protein restricted diet and L-carnitine, folic acid and Vitamin B12 supplementation were given for the patients with organic acidemia. L-carnitine was given to the patients with primary carnitine deficiency. The overall epidemiology, prognosis, follow-up of the screening program were also investigated in the neonates. RESULT: A total of 129 415 neonates were investigated for 26 inborn errors of metabolism during the period. Twenty-three newborns were confirmed as having inborn errors of metabolism, including 13 with amino acidemias, 6 with organic acidemias and 4 with fatty acid oxidation disorders. The prevalence was 1:5626. Positive predictive value was 2.10%, specificity was 99.72% and sensitivity 100%. Seventeen children remain asymptomatic during the follow-up. Five patients had motor and mental developmental delay. One patient presented metabolic disorders during the follow-up. No death occurred in this series of patients. CONCLUSION: This strategy represents a valuable preventive medicine approach by enabling diagnosis and treatment before the onset of symptoms.


Assuntos
Erros Inatos do Metabolismo/diagnóstico , Triagem Neonatal/métodos , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Feminino , Seguimentos , Humanos , Recém-Nascido , Masculino , Erros Inatos do Metabolismo/metabolismo
12.
Chem Biodivers ; 7(12): 2917-30, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21162005

RESUMO

A rapid, sensitive, and specific method by high-performance liquid chromatography (HPLC) coupled to diode-array detection (DAD) and tandem mass spectrometry (MS) techniques was developed for the identification of absorbed constituents and their metabolites in rats after the oral administration of a Chai-Huang decoction (CHD), which consists of Bupleurum chinense and Scutellaria baicalensis in the proportion 1 : 1 (w/w). By comparing their retention times and MS data with those of authentic compounds and published data, a total of 14 compounds were identified in the CHD samples. In addition, eleven and seven compounds were characterized in the urine and serum samples of the rats, respectively. The results indicated that the main absorbed constituents were chrysin-6-C-arabinosyl-8-C-glucoside, chrysin-6-C-glucosyl-8-C-arabinoside, baicalin, wogonin-5-O-glucoside, oroxylin A-7-O-glucuronide, wogonoside, saikosaponin A, saikosaponin C, saikosaponin D, baicalein, and wogonin. These compounds might be responsible for the curative effects of the CHD. The findings demonstrated that the proposed method could be used to rapidly and simultaneously analyze and screen the multiple absorbed bioactive constituents in a formula of traditional Chinese medicines (TCM). This is very important not only for the pharmaceutical discovery process and the quality control of crude drugs but also to explain the mechanisms of action of TCM.


Assuntos
Bupleurum/química , Medicamentos de Ervas Chinesas/química , Scutellaria baicalensis/química , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/administração & dosagem , Flavanonas/urina , Flavonoides/urina , Glucosídeos/urina , Glucuronídeos/urina , Medicina Tradicional Chinesa , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/urina , Ratos , Saponinas/urina , Espectrometria de Massas por Ionização por Electrospray
13.
J Nat Prod ; 73(6): 1160-3, 2010 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-20476749

RESUMO

A new cadinane-type sesquiterpenoid, tatarinowin A (1), two phenylpropanoids, tatarinoids A (2) and B (3), and a trinorlignan, tatarinoid C (4), along with 15 known compounds including two pairs of mixtures were isolated from the rhizome of Acorus tatarinowii. The absolute configurations of 1-4 were established by computation of specific rotation values. The isolated compounds were evaluated for their cAMP regulatory activity by the AlphaScreen assay.


Assuntos
Acorus/química , AMP Cíclico/metabolismo , Medicamentos de Ervas Chinesas/isolamento & purificação , Lignanas/isolamento & purificação , Fenilpropionatos/isolamento & purificação , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Lignanas/química , Lignanas/farmacologia , Estrutura Molecular , Fenilpropionatos/química , Fenilpropionatos/farmacologia , Rizoma/química , Sesquiterpenos/química
14.
Biomed Chromatogr ; 24(11): 1147-51, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20120039

RESUMO

To profile the anti-Coxsackie virus B3 constituents of Radix Astragali, an HPLC-DAD-MS(n) analytical method, combined with an in vivo test, has been developed to identify the constituents of the active part, which has been demonstrated to have potency to inhibit the proliferation of virus in cardiac muscle, alleviate infraction in heart and elevate the survival rate of the animal. By comparing their retention time and MS data with those obtained from the authentic compounds and the published data, a total of 19 compounds, including 11 isoflavonoids and eight saponins, were identified, among which one pterocarpane glucoside was reported for the first time. The present study provides an approach to rapidly screening bioactive constituents in traditional Chinese medicines.


Assuntos
Antivirais/análise , Astrágalo (Planta)/química , Cromatografia Líquida de Alta Pressão/métodos , Extratos Vegetais/análise , Espectrometria de Massas por Ionização por Electrospray/métodos , Animais , Antivirais/farmacologia , Infecções por Coxsackievirus/tratamento farmacológico , Infecções por Coxsackievirus/virologia , Enterovirus Humano B/efeitos dos fármacos , Células Hep G2 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/farmacologia
15.
Magn Reson Chem ; 46(12): 1195-7, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18802971

RESUMO

Two new iridoid diastereoisomers (1, 2), together with five known compounds, were isolated from the flowers of Plumerian rubra L. cv. acutifolia. Their structures were elucidated by the means of in-depth spectroscopic and mass-spectrometric analyses, particularly 1D and 2D NMR spectroscopy.


Assuntos
Apocynaceae/química , Iridoides/química , Espectroscopia de Ressonância Magnética/métodos , Flores/química , Espectrometria de Massas , Estrutura Molecular , Estereoisomerismo
16.
J Asian Nat Prod Res ; 10(1-2): 177-84, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18253886

RESUMO

By the guidance of bioassay, one new cytotoxic triterpenoid saponin, 3-O-[beta-D-galactopyranosyl-(1-->2)-beta-D-glucuronopyranosyl] quillaic acid 28-O-beta-D-glucopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-[beta-D-fucopyranosyl-(1-->4)]-beta-D-fucopyranoside (1), and five known cytotoxic triterpenoid saponins, vaccaroside E (2), vaccaroside G (3), vaccaroside B (4), segetoside H (5) and segetoside I (6), were isolated from Vaccaria segetalis. Their structures were established on the basis of ESI-MS, IR, extensive NMR ((1)H NMR, (13)C NMR, TOCSY, (1)H-(1)H COSY, DEPT, HMQC, HMBC and ROESY) analyses, chemical degradation, and by comparing with previously reported data. Compounds 1-6 showed moderate cytotoxic activities against LNcap, P-388 and A-549 cell lines with IC(50) values in the range 0.1-12.9 microM.


Assuntos
Antineoplásicos Fitogênicos/química , Saponinas/química , Saponinas/farmacologia , Triterpenos/química , Triterpenos/farmacologia , Vaccaria/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Humanos , Estrutura Molecular , Neoplasias/tratamento farmacológico
17.
J Pharm Biomed Anal ; 45(5): 793-8, 2007 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-17723287

RESUMO

Four metabolites of mangiferin were firstly isolated and identified from rat urine. The structures of the four metabolites were determined to be 1,3,7-trihydroxyxanthone (M-1), 1,3,6,7-tetrahydroxyxanthone (M-2), 1,3,6-trihydroxy-7-methoxyxanthone (M-3) and 1,7-dihydroxyxanthone (M-4), respectively. A simple and specific analytical method for determination of the four metabolites in rat urine was developed by high performance liquid chromatography (HPLC). Quercetin was employed as an internal standard. The correlation coefficients of the calibration curves were higher than 0.997, both intra- and inter-day precision of four metabolites were determined and their R.S.D. did not exceed 10%. The accuracy and linear range had been investigated in detail. The cumulative urinary excretions of the four metabolites were measured and the possible metabolic pathway of the metabolites was discussed.


Assuntos
Xantonas/isolamento & purificação , Xantonas/urina , Administração Oral , Anemarrhena/anatomia & histologia , Animais , Calibragem , Cromatografia Líquida de Alta Pressão/métodos , Estabilidade de Medicamentos , Masculino , Medicina Tradicional Chinesa , Estrutura Molecular , Raízes de Plantas/química , Quercetina/química , Ratos , Ratos Sprague-Dawley , Padrões de Referência , Reprodutibilidade dos Testes , Temperatura Ambiente , Fatores de Tempo , Xantonas/administração & dosagem , Xantonas/química , Xantonas/metabolismo
18.
Biomed Chromatogr ; 21(5): 458-62, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17370292

RESUMO

A high-performance liquid chromatographic method with UV detection has been developed for the determination of saikosaponin a in rat plasma. Saikosaponin a and internal standard jujuboside A were isolated from plasma samples by solid-phase extraction. The chromatographic separation was achieved on a reversed-phase C(18) column with the mobile phase of acetonitrile-water (35:65, v/v) at a flow rate of 1 mL/min and UV detection was set at 205 nm. The standard curve for saikosaponin a was linear over the concentration range 0.25-10 microg/mL and the limit of detection was 0.05 microg/mL. The absolute recovery was greater than 82%. The precision and accuracy ranged from 3.05 to 9.59% and 95.61 to 110.00%, respectively. The validated method was used to determine saikosaponin a in plasma samples in a pharmacokinetic study of saikosaponin a administered to Sprague-Dawley rats.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Ácido Oleanólico/análogos & derivados , Saponinas/sangue , Espectrofotometria Ultravioleta/métodos , Animais , Calibragem , Ácido Oleanólico/administração & dosagem , Ácido Oleanólico/sangue , Ácido Oleanólico/farmacocinética , Ratos , Ratos Sprague-Dawley , Padrões de Referência , Reprodutibilidade dos Testes , Saponinas/administração & dosagem , Saponinas/farmacocinética , Espalhamento de Radiação , Sensibilidade e Especificidade
19.
Biomed Chromatogr ; 21(6): 655-60, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17370298

RESUMO

Anti-DHBV (duck hepatitis B virus) activity was found in the aqueous extracts of Sophora flavescens Ait. in vivo. Liquid chromatography/electrospray ionization ion trap mass spectrometry was applied to characterize the components in duck serum after oral administration of S. flavescens extract. Oxymatrine (1), sophoranol (2), sophoridine (3) and matrine (4) were identified in the serum. Further research on the four compounds was evaluated for their antiviral activity against HBV (hepatitis B virus) in cell culture. The results suggested that oxymatrine, sophoranol and matrine were the efficacy substances for anti-HBV activity in aqueous extracts of S. flavescens Ait.


Assuntos
Antivirais/administração & dosagem , Cromatografia Líquida de Alta Pressão/métodos , Infecções por Hepadnaviridae/tratamento farmacológico , Vírus da Hepatite B do Pato/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Espectrometria de Massas por Ionização por Electrospray/métodos , Replicação Viral/efeitos dos fármacos , Alcaloides/sangue , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Patos , Flavonoides/sangue , Formazans/química , Formazans/metabolismo , Infecções por Hepadnaviridae/virologia , Vírus da Hepatite B do Pato/isolamento & purificação , Vírus da Hepatite B do Pato/fisiologia , Estrutura Molecular , Quinolizinas/sangue , Sophora/química , Espectrofotometria Ultravioleta/métodos , Sais de Tetrazólio/química , Sais de Tetrazólio/metabolismo
20.
Biomed Chromatogr ; 21(7): 762-7, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17385799

RESUMO

A reversed-phase high-performance liquid chromatographic (HPLC) assay for calycosin-7-O-beta-D-glucopyranoside in rat plasma and urine with solid-phase extraction (SPE) was developed. Rutin was employed as an internal standard. The mobile phase consisted of acetonitrile-water (16:84, v/v) at a flow rate of 1.0 mL/min. Detection was set at 280 nm. The limit of quantitation of calycosin-7-O-beta-D-glucopyranoside was 0.2 microg/mL in both plasma and urine. The standard curve was linear from 0.2 to 10.0 microg/mL in plasma, and 0.2 to 5.0 microg/mL in urine. Both intra- and inter-day precision of the calycosin-7-O-beta-d-glucopyranoside were determined and their RSD did not exceed 10%. The method was successfully applied to the analysis of samples obtained from a basic pharmacokinetic study, in which calycosin-7-O-beta-d-glucopyranoside was administered orally to rats.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Glucosídeos/farmacocinética , Isoflavonas/farmacocinética , Animais , Glucosídeos/sangue , Glucosídeos/urina , Isoflavonas/sangue , Isoflavonas/urina , Masculino , Ratos , Ratos Sprague-Dawley , Padrões de Referência , Sensibilidade e Especificidade
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