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1.
AAPS PharmSciTech ; 21(2): 38, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31897797

RESUMO

In the study, we developed a novel oral dosage form of Compound Danshen to resolve the problems of low bioavailability, disequilibrium in drug release, and stomach degradation of active components of Compound Danshen in conventional formulas. A colon-specific osmotic pump capsule (COPC) of Compound Danshen was prepared using a semipermeable shell with the core components. Using a single-factor method, we obtained the optimal formulation that consisted of Salvia miltiorrhiza extract, Panax notoginseng extract, Borneol, sodium chloride, polyethylene oxide wsr-N10, hydroxypropyl-ß-cyclodextrin, and ludipress. Moreover, in vitro dissolution test showed simultaneous releases of active ingredients from Compound Danshen COPC over 12 h at pH 7.8, displaying zero-order release characteristics. The impetus of drug release mainly depended on the difference in osmotic pressure across the capsule shell. Next, scanning electron microscopy showed morphological changes in the capsule shell during the dissolution test. More importantly, pharmacokinetic study in beagle dogs indicated that relative bioavailability was 330.58% and retention time was greatly prolonged in Compound Danshen COPC, compared with those in marketed Compound Danshen tablet products. Finally, in vivo imaging studies in beagle dogs showed that COPC was stable in gastrointestinal tract and the drug was specifically released in the colon region. A colon-specific osmotic pump capsule (COPC) of Compound Danshen was developed and optimized to achieve simultaneous zero-order release of multiple active components of Compound Danshen in the colon. More importantly, the COPC have proved to improve the bioavailability and prolong the retention time of Compound Danshen, compared with those in a marketed product.


Assuntos
Formas de Dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Administração Oral , Animais , Disponibilidade Biológica , Colo/metabolismo , Preparações de Ação Retardada , Cães , Composição de Medicamentos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinética , Excipientes , Pressão Osmótica , Panax notoginseng/química , Salvia miltiorrhiza/química , Solubilidade
2.
Toxicol Lett ; 323: 41-47, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31982501

RESUMO

Gynura japonica (also named Tusanqi in Chinese) is used as a folk herbal medicine for treating blood stasis or traumatic injury. However, hundreds of hepatic sinusoidal obstruction syndrome (HSOS) cases have been reported after consumption of preparations made from G. japonica because it contains large amounts of hepatotoxic pyrrolizidine alkaloids (PAs). To date, blood pyrrole-protein adducts (PPAs) are suggested as biomarkers for the diagnosis of PA-induced HSOS in clinics. However, the concentration of PPAs in the blood is greatly affected by several factors including the amount of PA exposure, herb intake period, and blood sampling time after the last exposure. In present study, the kinetic characters of PPAs in serum and liver as well as other potential target organs were studied systematically and comprehensively following multiple exposures of PAs in G. japonica extract (GJE). As results, PPAs content reached to a plateau both in serum and liver after the mice were treated with GJE for 2 weeks on daily basis. PPAs cleared significantly slower in liver (T1/2ke∼184.6 h, ∼7.7 days) than in serum (T1/2ke∼95.8 h, ∼4.0 days). Although more than 90 % PPAs were removed 2 weeks after the last dosing, PPAs still persisted in the liver until the end of the experiment, i.e. 8 weeks after the last dosing. The results would be of great help for understanding the importance of PPAs for PA-induced toxicity and its detoxification.


Assuntos
Proteínas Sanguíneas/metabolismo , Medicamentos de Ervas Chinesas/farmacocinética , Hepatopatia Veno-Oclusiva/induzido quimicamente , Pirróis/metabolismo , Alcaloides de Pirrolizidina/farmacocinética , Animais , Medicamentos de Ervas Chinesas/toxicidade , Cinética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/análise , Extratos Vegetais/toxicidade , Alcaloides de Pirrolizidina/toxicidade
3.
Biomed Chromatogr ; 34(2): e4706, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31629372

RESUMO

Zhiqiao Gancao (ZQGC) decoction is widely used in China due to its therapeutic effect on lumbar disc herniation (LDH). In this study, we compared the clinical therapeutic effects among oral ZQGC decoction treatment, bed rest, and oral anti-inflammatory drug celecoxib treatment using visual analog scale, Oswestry Disability Index, and MacNab scores. The results showed that ZQGC decoction can significantly improve the symptoms of patients with LDH. A selective, sensitive, and rapid ultra-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of eight bioactive components in rat plasma. The plasma samples were extracted by simple protein precipitation with methanol. The protonated analytes were quantitated simultaneously in positive and negative ion modes by multiple reaction monitoring with a mass spectrometer. The calibration curve of eight components in plasma showed good linearity (r > .996) and the extraction recovery was 81.19% ± 2.15% - 100.39 ± 3.36 (relative standard deviation: 1.21%-10.70%). The accuracy of all the lower limit of quantitation values was quantified within 80%-120%, and the precision was less than 15%. This validated method was successfully applied to the pharmacokinetics study in rat plasma after ZQGC decoction oral treatment. Our research can provide experimental basis for the rational clinical application of ZQGC decoction in the treatment of LDH.


Assuntos
Analgésicos/uso terapêutico , Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/uso terapêutico , Administração Oral , Analgésicos/administração & dosagem , Analgésicos/sangue , Analgésicos/farmacocinética , Animais , Curcumina/análise , Curcumina/farmacocinética , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/análise , Flavonas/sangue , Flavonas/farmacocinética , Ácido Glicirretínico/sangue , Ácido Glicirretínico/farmacocinética , Humanos , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/fisiopatologia , Deslocamento do Disco Intervertebral/tratamento farmacológico , Deslocamento do Disco Intervertebral/fisiopatologia , Modelos Lineares , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
4.
Chem Biol Interact ; 315: 108851, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31614129

RESUMO

BACKGROUND: Currently, few herbal pharmacokinetic (PK) parameters have been applied successfully for therapeutic monitoring because of the complexity of consistency when there are multiple chemicals and efficacies. PURPOSE: The present study aims to evaluate the herbal PK properties by investigating the PK parameters of the 8 absorbed bioactive compounds (ABCs), which can represent its parent herbal holistic efficacy, to achieve a PK therapeutic monitoring of herbs. METHOD: First, we tested the hypothesis that the antidepressant and prokinetic effects and related anti-inflammation and anti-oxidation activity (APIO) by Fructus aurantii-Magnolia Bark (FM) formula are related to 8 compounds according to the absorbable evidence and the determined contents. Subsequently, stable and representative APIO from 8ABCs allowed us to develop a sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of 8 compounds following the oral administration of FM decoction (20 g/kg) in rats. RESULT: 8 compounds either including Meranzin hydrate (MH) or MH alone almost identically (8 compounds: 91.62-108.82%)or nearly(MH: 65.38-88.41%) replicated the parent formula FM in terms of efficacy for inducing APIO. CONCLUSION: This unifying strategy shows how multi-herb formulas pharmacokinetic therapeutic monitoring can be achieved by the method we established.


Assuntos
Anti-Inflamatórios/farmacocinética , Antidepressivos/farmacocinética , Antioxidantes/farmacocinética , Medicamentos de Ervas Chinesas/química , Magnolia/química , Casca de Planta/química , Animais , Cromatografia Líquida de Alta Pressão/métodos , Cumarínicos/farmacocinética , Medicamentos de Ervas Chinesas/farmacocinética , Frutas/química , Cinética , Masculino , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem/métodos
5.
Biomed Chromatogr ; 34(2): e4757, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31755125

RESUMO

Er-Zhi-Wan (EZW) is a traditional Chinese medicine with many clinical applications and used as a health product in East Asia. Five active ingredients (salidroside, specnuezhenide, nuezhenoside, luteolin, and oleanolic acid) were screened out from EZW to develop an in vitro rapid evaluation method for the classification of in vivo drug absorption behavior by biopharmaceutics classification system (BCS). Ultra-performance liquid chromatography was used for quantitative analysis. Solubility and permeability were assayed by equilibrium solubility and multiple models: everted rat intestinal sac model, cultured Caco-2 cells, octanol-water partition coefficient (LogP) method. The BCS properties of drugs were predicted using software applications, and the correlations of measured and predicted values of factors affecting oral drug absorption were calculated. The results were verified by measuring the absolute bioavailability of the active ingredients. Salidroside, specnuezhenide, and nuezhenoside were classified as BCS class III drugs, and luteolin was classified as a BCS class III/I drug because of the difference in LogP and intestinal permeability. Oleanolic acid was classified as a BCS class II/IV drug in acidic media and BCS class I/III drug in other media. Overall, EZW may be classified as a BCS class III drug, and permeability was identified as the primary factor limiting absorption. The results provide a novel method for the evaluation of the in vivo absorption of oral traditional Chinese medicines.


Assuntos
Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/farmacocinética , Animais , Disponibilidade Biológica , Células CACO-2 , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Glucosídeos/sangue , Glucosídeos/química , Glucosídeos/farmacocinética , Humanos , Absorção Intestinal/fisiologia , Limite de Detecção , Modelos Lineares , Luteolina/sangue , Luteolina/química , Luteolina/farmacocinética , Masculino , Ácido Oleanólico/sangue , Ácido Oleanólico/química , Ácido Oleanólico/farmacocinética , Permeabilidade , Fenóis/sangue , Fenóis/química , Fenóis/farmacocinética , Piranos/sangue , Piranos/química , Piranos/farmacocinética , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Software , Solubilidade
6.
J Mass Spectrom ; 55(1): e4484, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31786817

RESUMO

Qixianqingming granules (QXQM) comprise a traditional Chinese medicine (TCM) formula that was developed based on the combination of TCM theory and clinical practice. This formula has been proven to effectively treat asthma. In this study, an analytical procedure using ultraperformance liquid chromatography, coupled with electrospray ionization quadrupole time-of-flight mass spectrometry, was established for the rapid separation and sensitive identification of the chemical components in QXQM and its metabolites in serum of rats. Seventy-two compounds were systematically identified in QXQM, including flavonoids, terpenoids, anthraquinones, phenylethanoid glycosides, stilbenes, alkaloids, and organic acids. Thirteen prototype compounds and 29 metabolites were detected in the serum of rats. The results provided fundamental information for further studying the mechanisms and clinical application of QXQM.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos , Alcaloides/análise , Alcaloides/metabolismo , Animais , Antraquinonas/análise , Antraquinonas/metabolismo , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/metabolismo , Flavonoides/análise , Flavonoides/metabolismo , Glicosídeos/análise , Glicosídeos/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Estilbenos/análise , Estilbenos/metabolismo , Terpenos/análise , Terpenos/metabolismo
7.
J Ethnopharmacol ; 247: 111576, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-30385423

RESUMO

AIM OF THE STUDY: Because the toxicity and efficacy of arsenic is closely related to its chemical species, we conducted examinations of arsenic species accumulation and distribution in the rat body after one-time and 30-day realgar administration and then elucidated the probable roles of different arsenic species in the short-term toxicity of realgar. MATERIALS AND METHODS: According to ICH M3 guidelines for non-clinical repeated dose toxicity studies and OECD Test guideline TG407 "Repeated Dose 28-Day oral Toxicity Study in Rodents, the doses of realgar set were 10.6 mg/kg, 40.5 mg/kg and 170 mg/kg. Rats were orally administered with realgar for one-tme and 30 days, respectively. Thereafter, biological samples (plasma, urine, liver, kidney, and brain) were obtained from rats and analyzed using high-performance liquid chromatography-inductively coupled plasma-mass spectrometry (HPLC-ICP-MS) to determine realgar metabolism, arsenic species accumulation and distribution. Additionally, the toxicity of realgar in rats was evaluated. RESULTS: The absorption, distribution and elimination half-life of total arsenic species in realgar were 3.33 hs, 16.08 hs and 24.65 hs, respectively. After 30 days of oral administration of realgar in rats, no significant drug-related toxicity occurred in the rats. Dimethylarsenic acid (DMA) is the most abundant arsenic species. The DMA contents of the liver and kidney of the high-dose realgar group were approximately 40-fold and 50-fold higher than those in the corresponding tissues of the control group, respectively. The arsenic species (III) was mainly detected in the liver and its content was about 40-fold higher than that of the control group. MMA was mainly detected in rat kidney, and the MMA content of the realgar treatment group was more than 2000 times higher than that of the control group. CONCLUSIONS: Arsenic is rapidly absorbed and distributed over the liver, kidneys and brain, and the distribution and elimination of arsenic in the blood is slow. The realgar doses corresponded to human equivalent doses (HED) of 1.7, 6.4 and 27.2 mg/kg, respectively. Considering that humans are 10 times more sensitive than animals, the realgar dose is equivalent to 0.17, 0.64 and 2.7 mg/kg HED. It can be considered that if patients take no more than 2.7 mg/kg realgar for 2 weeks, there will be no adverse reactions.


Assuntos
Arsenicais/farmacocinética , Sulfetos/farmacocinética , Administração Oral , Animais , Arsenicais/administração & dosagem , Encéfalo/metabolismo , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/toxicidade , Feminino , Absorção Gastrointestinal , Meia-Vida , Rim/metabolismo , Fígado/metabolismo , Masculino , Espectrometria de Massas , Ratos , Sulfetos/administração & dosagem , Sulfetos/toxicidade , Distribuição Tecidual , Testes de Toxicidade Aguda
8.
J Pharm Biomed Anal ; 177: 112836, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31473481

RESUMO

Xian-Ling-Gu-Bao capsule (XLGB) is an effective traditional Chinese medicine prescription (TCMP) that is used for the prevention and treatment of osteoporosis in China. A rapid, simple, efficient and stable method based on UPLC-MS/MS technology was developed for simultaneous determination of multiple components of XLGB in rat plasma. Mass spectrometric detection was performed in multiple reaction monitoring (MRM) mode with electrospray ionization (ESI). For twenty-one selected quantitative prototypes, all calibration curves showed favourable linearity (r>0.9932) in linear ranges. The lower limits of quantification (LLOQs) were 2 ng/mL for psoralen (PL), 2.5 ng/mL for asperosaponin VI (AS), 1 ng/mL for isopsoralen (IPS) and sweroside (SW), 0.5 ng/mL for magnoflorine (MA), bavachinin (BVN), tanshinone IIA (TA), timosaponin BII (TBII) and icaritin (ICT), 0.1 ng/mL for epimedin B (EB) and epimedin C (EC), 0.05 ng/mL for icariin (IC), isobavachalcone (IBC), psoralidin (PD), bavachin (BV), bavachalcone (BC), epimedin A (EA) and isobavachin (IBV), 0.02 ng/mL for neobavaisoflavone (NEO) and icariside I (ICI) and 0.01 ng/mL for icariside II (ICII). The intra-day and inter-day (low, medium, high) precision (relative standard deviation) for all analytes was less than 8.63%, and the accuracies (as relative error) were in the range of -12.45% to 8.91%. Extraction recoveries and matrix effects of analytes and IS were acceptable. All analytes were stable during the assay and storage in plasma samples. The validated method was successfully applied to the pharmacokinetics (PK) studies of the twenty-one prototypes at pharmacodynamic doses (0.3 and 1 g/kg/day). In addition, dynamic profiles of 28 metabolites (phase II conjugates: 23 glucuronide conjugates, 2 sulfate conjugates and 3 glucuronide or sulfate conjugates) were also monitored by their area/IS area-time curves. As a result, coumarins, prenylated flavonoids from Psoraleae Fructus, alkaloids and prenylated flavonol glycosides from Epimedii Herba, and iridoid glycosides, triterpenoid saponins from Dipsaci Asperoidis Radix were considered to be the key effective substances of XLGB due to their high exposure and appropriate pharmacokinetic features. This is the first report to reveal pharmacodynamic ingredients by a reversed pharmacodynamic (PD) - pharmacokinetics (PK) study.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Espectrometria de Massas em Tandem/métodos , Administração Oral , Animais , Aporfinas/administração & dosagem , Aporfinas/sangue , Aporfinas/farmacocinética , Cápsulas , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/análise , Feminino , Ficusina/administração & dosagem , Ficusina/sangue , Ficusina/farmacocinética , Flavonoides/administração & dosagem , Flavonoides/sangue , Flavonoides/farmacocinética , Furocumarinas/administração & dosagem , Furocumarinas/sangue , Furocumarinas/farmacocinética , Glucosídeos Iridoides/administração & dosagem , Glucosídeos Iridoides/sangue , Glucosídeos Iridoides/farmacocinética , Modelos Animais , Ratos , Saponinas/administração & dosagem , Saponinas/sangue , Saponinas/farmacocinética
9.
J Pharm Biomed Anal ; 177: 112835, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31499428

RESUMO

Tuberculosis of cervical lymph nodes is called scrofula in Traditional Chinese Medicine (TCM). Clinical manifestation is that unilateral or bilateral neck can have multiple enlarged lymph nodes of different sizes. Current therapeutic drugs include Lysionotus pauciflorus Maxim. tablets and compound of Lysionotus pauciflorus Maxim., which have a significant effect on tuberculosis of cervical lymph nodes. This compound is composed of three herbs, Lysionotus pauciflorus Maxim., Prunella vulgaris L. and Artemisia argyi Levl.et Vant. A selective and sensitive LC-MS/MS method was established and validated in rat plasma for the first time. Chromatographic separation was achieved on a Wonda Cract ODS-2 C18 Column (150 mm × 4.6 mm, 5 µm). The mobile phase contained 0.1% formic acid aqueous solution and acetonitrile with a flow rate of 0.8 mL/min. The detection was performed in negative electrospray ionization mode and the precursor/product ion transitions of six components and internal standard (IS) sulfamethoxazole were quantified in multiple reaction monitoring (MRM) using QTRAP-3200 MS/MS. The method fulfilled US Food and Drug Administration guidelines for selectivity, sensitivity, accuracy, precision, matrix effect, extraction recovery, dilution integrity, and stability. This proposed method was then successfully applied to a pharmacokinetic study after oral administration of 10 mL/kg compound extracts in rats. The pharmacokinetic parameters and plasma concentration-time profiles would prove valuable in pre-clinical and clinical investigations on the disposition of compound medicine.


Assuntos
Medicamentos de Ervas Chinesas/análise , Lamiales/química , Espectrometria de Massas em Tandem/métodos , Administração Oral , Animais , Ácidos Cafeicos/administração & dosagem , Ácidos Cafeicos/sangue , Ácidos Cafeicos/farmacocinética , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacocinética , Flavonas/administração & dosagem , Flavonas/sangue , Flavonas/farmacocinética , Glucosídeos/administração & dosagem , Glucosídeos/sangue , Glucosídeos/farmacocinética , Masculino , Modelos Animais , Fenilpropionatos/administração & dosagem , Fenilpropionatos/sangue , Fenilpropionatos/farmacocinética , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray/métodos , Comprimidos , Tuberculose dos Linfonodos/tratamento farmacológico
10.
J Pharm Biomed Anal ; 177: 112856, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31521020

RESUMO

Daphne genkwa Sieb. et Zucc., as a traditional oriental herb, has been widely distributed and employed in China. The major bioactive components in D. genkwa are flavonoid compounds, which showed pharmacological activities such as anti-inflammatory, analgesic, anti-tumor and immunomodulatory activities. In this study, we analyzed total flavonoids in D. genkwa and their metabolites in normal and adjuvant arthritis (AA) rat plasma, urine and feces samples by liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS). A total of 4 metabolites in plasma, 9 metabolites in urine and 15 metabolites in feces were characterized respectively by LC-Q-TOF-MS technology in normal rat. And 9 of the metabolites were observed in the AA rat urine, while there was no prototype drug or its metabolites detected in plasma and fecal samples. The metabolic pathway mainly involves hydroxylation, methylation, glucuronide, sulfate conjugation, oxidation and reduction, during the phase I and phase II biotransformation pathway. All the information gained here will be greatly helpful in elucidating the potential biological and pharmacological mechanism of flavonoid in D. genkwa, thus providing new ideas for drug development.


Assuntos
Artrite Experimental/tratamento farmacológico , Daphne/química , Medicamentos de Ervas Chinesas/farmacocinética , Flavonoides/farmacocinética , Administração Oral , Animais , Artrite Experimental/sangue , Artrite Experimental/imunologia , Artrite Experimental/urina , Cromatografia Líquida de Alta Pressão , Sistema Enzimático do Citocromo P-450/metabolismo , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Fezes/química , Flavonoides/administração & dosagem , Flavonoides/química , Adjuvante de Freund/administração & dosagem , Adjuvante de Freund/imunologia , Glucuronosiltransferase/metabolismo , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Distribuição Tecidual
11.
J Pharm Biomed Anal ; 177: 112876, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31525575

RESUMO

Flavonoids-enriched extract from Scutellaria baicalensis roots (FESR) ameliorated influenza A virus (IAV) induced acute lung injury (ALI) in mice by inhibiting the excessive activation of complement system in vivo. However, FESR had no anti-complementary activity in vitro. In order to reveal the effective materials of FESR for the treatment of IAV-induced ALI, the present research explored the metabolic process of FESR both in nomal and IAV infected mice by the method of UHPLC-ESI-LTQ/MS, as well as the metabolic activating mechanism. The results showed that the inactive flavonoid glycosides of FESR were partly metabolized into anti-complementary aglycones in vivo, mainly including 5,7,4'-trihydroxy-8-methoxy-flavone, norwogonin, baicalein, wogonin, oroxylin A and chrysin. Moreover, compared with the normal mice, IAV-induced ALI mice exhibited more efficient on producing and absorbing these active metabolites, with AUC0-t and Cmax in plasma and concentrations in lungs and intestines markedly elevated in the IAV treated groups (P <  0.05). Interestingly, the intestinal bacteria from IAV-induced ALI mice showed stronger ß-glucuronidase activity and also had higher efficiency on transforming FESR to the flavonoid aglycones. These findings suggested that the anti-complementary aglycones produced by metabolic activation in vivo should be the potential effective materials of FESR against IAV infections, and intestinal bacteria might play an important role on the higher bioavailability of FESR in IAV infected mice. Additionally, the animals under the pathological state are more suitable for the metabolic study of traditional Chinese medicine.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Inativadores do Complemento/farmacocinética , Medicamentos de Ervas Chinesas/farmacocinética , Flavonoides/farmacocinética , Influenza Humana/tratamento farmacológico , Scutellaria baicalensis/química , Ativação Metabólica , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/virologia , Animais , Inativadores do Complemento/administração & dosagem , Inativadores do Complemento/química , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Flavonoides/administração & dosagem , Microbioma Gastrointestinal/fisiologia , Glucuronidase/metabolismo , Humanos , Vírus da Influenza A/imunologia , Vírus da Influenza A/patogenicidade , Influenza Humana/metabolismo , Influenza Humana/virologia , Pulmão/patologia , Camundongos , Raízes de Plantas/química , Organismos Livres de Patógenos Específicos
12.
J Pharm Biomed Anal ; 177: 112869, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31539714

RESUMO

A rapid, sensitive, selective, and accurate UPLC-MS/MS method was developed and fully validated for the simultaneous determination of quercitrin, phloridzin, quercetin, and phloretin in rat plasma after oral administration of Malus hupehensis (Pamp.) Rehd extracts. The pharmacokinetic parameters of oral phloridzin monomer and phloridzin in the extract were also compared. Plasma samples were processed with a simple protein precipitation technique using methanol, followed by chromatographic separation using a Sun Fire ™C18 column. Bergenin was used an internal standard (IS). A 15.0 min linear gradient elution was used at a flow rate of 0.8 mL/min with a mobile phase of 0.1% formic acid in water and acetonitrile. The analytes and IS were detected using negative ion electrospray ionization in multiple reaction monitoring mode. The developed method exhibited good linearity (r ≥ 0.9911), and the lower limits of quantification ranged from 0.2 to 0.8 ng/mL for the four analytes. Intra-day and inter-day precision were both less than 8.5% and were within the acceptable limits. Matrix effect and recovery efficiency of all analytes were found to be >76.2% and >71.4%, respectively. Stability results showed that the analytes were stable at all conditions. Additionally, the carry-over effect and dilution effect were within the acceptance range. The developed method was successfully applied to a pharmacokinetic study of four analytes in rats after oral administration of Malus hupehensis (Pamp.) Rehd. extracts.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Flavonoides/farmacocinética , Malus/química , Chás de Ervas , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/análise , Flavonoides/administração & dosagem , Flavonoides/sangue , Masculino , Modelos Animais , Folhas de Planta/química , Ratos , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos
13.
J Pharm Biomed Anal ; 177: 112874, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31542420

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disease that seriously affects daily life. Schisandra chinensis (Turcz.) Baill. Fructus (SCF) and Alpinia oxyphylla Miq. Fructus (AOF) have been regarded as classical herbs for dementia since ancient times. Alpinia oxyphylla Miq.-Schisandra chinensis (Turcz.) Baill. herb pair (ASHP) is the compatible form of the two herbs. Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established for the simultaneous determination of protocatechuic acid, chrysin, schisandrin, gomisin A, gomisin B, nootkatone, deoxyschizandrin, schisandrin B and schisandrin C in rat plasma. The pharmacokinetic differences of the above nine active components in normal rats and AD model rats after oral administration of SCF, AOF, and ASHP ethanol extracts were investigated. Chloramphenicol and bifendate were used as the internal standards. Extraction of plasma sample was by liquid-liquid extraction with ethyl acetate. A SBC18 column (2.1 mm × 100 mm, 1.8 µm) was used in this experiment at a flow rate of 0.3 mL/min at 30 °C with linear gradient elution using acetonitrile and water containing 0.1% formic acid. This study showed ASHP can improve the absorption of protocatechuic acid, chrysin, schisandrin, gomisin B, nootkatone, deoxyschizandrin, schisandrin B and schisandrin C in vivo and slow down part of these components' elimination. In addition, compared with normal rats, the pharmacokinetic parameters changed significantly in AD model rats' plasma after oral administration of ASHP. Hence, these may be the pharmacokinetic mechanism of ASHP, in addition to serving as a potential agent in the treatment of AD.


Assuntos
Alpinia/química , Doença de Alzheimer/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Medicamentos de Ervas Chinesas/farmacocinética , Schisandra/química , Administração Oral , Doença de Alzheimer/sangue , Doença de Alzheimer/etiologia , Peptídeos beta-Amiloides/administração & dosagem , Peptídeos beta-Amiloides/toxicidade , Animais , Cromatografia Líquida de Alta Pressão/métodos , Modelos Animais de Doenças , Combinação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Humanos , Injeções Intraventriculares , Masculino , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/toxicidade , Ratos , Espectrometria de Massas em Tandem/métodos
14.
J Pharm Biomed Anal ; 177: 112885, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31563759

RESUMO

Tianma pills, a traditional formula made from Ligusticum chuanxiong and Gastrodia elata, are efficacious for the treatment of primary headache. Tetramethylpyrazine (TMP) and Ferulic acid (FA) are the bioactive ingredients of Ligusticum chuanxiong, while Gastrodin and Gastrodigenin are the bioactive ingredients of Gastrodia elata. Pharmacokinetic assessment of TMP, FA, gastrodin or gastrodigenin in blood or brain interstitial fluid (BIF) has been reported in healthy animals. However, the pharmacokinetic properties of TMP and FA have not been studied when they are co-administered in a blood-stasis migraine model. The present research investigated the pharmacokinetic behavior of TMP and FA after oral administration in the presence of different concentrations of gastrodin and gastrodigenin in a blood-stasis migraine model. Pharmacokinetic parameters were determined using blood-brain microdialysis in combination with the UHPLC-MS method. Compared to the control group, in which TMP and FA were administrated without gastrodin or gastrodigenin, the T1/2, MRT, Cmax and AUC0-∞ of TMP and FA were increased. These results indicate that varying concentrations of gastrodin and gastrodigenin play an important role in affecting the pharmacokinetics of TMP and FA. Low concentrations of gastrodin and gastrodigenin (similar to those found in Tianma pills) were more efficacious, validating the utility of the ancient formulation.


Assuntos
Barreira Hematoencefálica/metabolismo , Medicamentos de Ervas Chinesas/farmacocinética , Gastrodia/química , Ligusticum/química , Transtornos de Enxaqueca/tratamento farmacológico , Administração Oral , Animais , Álcoois Benzílicos/administração & dosagem , Álcoois Benzílicos/farmacocinética , Barreira Hematoencefálica/química , Barreira Hematoencefálica/citologia , Temperatura Baixa/efeitos adversos , Ácidos Cumáricos/administração & dosagem , Ácidos Cumáricos/farmacocinética , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Interações de Medicamentos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Líquido Extracelular/química , Glucosídeos/administração & dosagem , Glucosídeos/farmacocinética , Humanos , Masculino , Microdiálise , Transtornos de Enxaqueca/sangue , Transtornos de Enxaqueca/etiologia , Permeabilidade , Pirazinas/administração & dosagem , Pirazinas/farmacocinética , Ratos , Organismos Livres de Patógenos Específicos , Vasoconstrição/efeitos dos fármacos
15.
Artigo em Inglês | MEDLINE | ID: mdl-31877432

RESUMO

Gandou Decoction (GDD), a well-known traditional Chinese medicine prescription, has been widely used for decades in clinical practice to treat Wilson's disease (WD) in China. However, due to lack of in vivo metabolism research, the absorbed components and metabolites of GDD have not been fully elucidated. In this study, a rapid and high-throughput ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MSE) was applied to rapidly identify prototypes and metabolites after oral administration of GDD. On this basis, the possible metabolic pathways of the main prototypes were proposed between normal and copper-laden rats. As a result, a total of 89 GDD-related xenobiotics were detected in normal dosed rats, including 83 (36 prototypes and 47 metabolites) in plasma and 52 (21 prototypes and 31 metabolites) in liver; a total of 77 GDD-related xenobiotics were detected in copper-laden dosed rats, including 68 (31 prototypes and 37 metabolites) in plasma and 42 (19 prototypes and 23 metabolites) in liver. Our findings showed that anthraquinones, alkaloids and protostane triterpenoids as well as a few saponins, flavonoids, tannins and curcuminoids were the main absorbed chemical components of GDD in rat plasma; anthraquinones, protostane triterpenoids and curcuminoids were the major components in rat liver. Glucuronidation and sulfation were deduced to be the predominant metabolic pathways of GDD. Methylation, acetylation, reduction, hydroxylation, demethylation and deglycosylation were often occurred in the metabolic process. Furthermore, the holistic metabolic profile of GDD revealed that copper-laden rats and normal rats had certain differences in drug absorption and metabolism. This study offered a solid basis for ascertaining bioactive components and action mechanism of GDD.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas , Fígado , Espectrometria de Massas em Tandem/métodos , Alcaloides/análise , Alcaloides/farmacocinética , Animais , Antraquinonas/análise , Antraquinonas/farmacocinética , Cobre/administração & dosagem , Cobre/efeitos adversos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Metaboloma/efeitos dos fármacos , Metabolômica , Ratos , Triterpenos/análise , Triterpenos/farmacocinética
16.
Zhongguo Zhong Yao Za Zhi ; 44(22): 4932-4939, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31872603

RESUMO

This study is aimed to establish a method for the determination of baicalin,baicalin and purpurin in the plasma of rats after oral administration of Pudilan Xiaoyan Oral Liquid( PDL) by using liquid chromatography-mass spectrometry( LC-MS),analyze the pharmacokinetics of three components in rats,and investigate the effects of PDL on drug-metabolizing enzymes in rat liver. C18 column was used for liquid chromatography separation,with acetonitrile-water( containing 0. 2% formic acid) as the mobile phase for gradient elution. The mass spectrometry was detected by electrospray ion source( ESI) under multi-reaction monitoring mode( MRM),as well as positive and negative ion alternating mode. Plasma sample collection was performed by using an automatic blood collection meter for small animals. The pharmacokinetic parameters were calculated by Win Nonlin software. The total protein concentration of rat liver microsomes and the total enzyme content of CYP450 were determined by BCA method and spectrophotometry respectively. The methodological study in terms of linear range,recovery rate,precision and sample stability,was used to confirm that the LC-MS analysis method established in this experiment was simple,exclusive,accurate and reliable,and can meet the requirement of determining the content of baicalin,oroxindin and corynoline in plasma after PDL administration in rats. The drug-time curve showed that baicalin and oroxindin had a bimodal phenomenon,and the pharmacokinetic parameters indicated that baicalin,oroxindin and corynoline in PDL had certain drug-like properties. After 7 consecutive days of PDL administration,the rat liver coefficient,total liver microparticle protein and CYP450 enzyme content were increased,but there was no significant difference,indicating that PDL was less likely to develop drug-drug interaction based on CYP enzyme. The results of this experiment can provide reference for the research on in vivo efficacy and drug interaction of PDL as well as on its clinical application.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Espectrometria de Massas em Tandem , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Fígado , Ratos , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray
17.
Zhongguo Zhong Yao Za Zhi ; 44(22): 4947-4952, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31872605

RESUMO

An UPLC-MS/MS method simultaneously determining contents of quercetin-3-O-ß-D-glucose-7-O-ß-D-gentiobioside and sinapic acid in rats' plasma was firstly established and applied to study the effects of processing on pharmacokinetics of Descurainiae Semen's active constituents. Complantatoside A as internal standard,methanol used for protein precipitation,the method was validated according to the instructions of CFDA. Rats' plasma was collected after being oral administrated equal dosage of 60% ethanal extract of raw or processed Descurainiae Semen at different point of time,then the concentrations were determined to calculate pharmacokinetic parameters using DAS 3. 2. 6. And the parameters were analyzed using SPSS 23. 0,meantime the concentration-time curve was drawn.The results showed that processing had no effects on the pharmacokinetics of QGG,but could improve the absorption of sinapic acid and slow down the excretion.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem
18.
Zhongguo Zhong Yao Za Zhi ; 44(20): 4454-4459, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31872632

RESUMO

To evaluate the pharmacodynamic effect of Siwu Decoction in treating blood deficiency in mice under multidimensional pharmacodynamic indexes by factor analysis. The mouse blood deficiency model was established with cyclophosphamide combined with acetophenone; and mouse organ index,white blood cells,red blood cell,hemoglobin,platelet counts in whole blood,serum granulocyte-macrophage colony-stimulating factor,macrophagecolony-stimulating factor,promotion erythropoietin,interleukin-3 and interleukin-6 were used as indicators to characterize the blood-enriching effect of Siwu Decoction; the pharmacodynamic effect of Siwu Decoction on blood deficiency model was evaluated comprehensively by factor analysis. Four common factors were extracted from 14 pharmacodynamics indexes through the factor analysis,namely blood phase factor,viscera index,hematopoietic regulatory factor 1-spleen index and hematopoietic regulatory factor 2-viscera index. The cumulative contribution rate of variance reached 86. 581%. The comprehensive score of factor analysis showed that Siwu Decoction had the best effect on blood replenishment,and it is significant compared with the model group( P<0. 01). The effect of alcohol precipitation of Siwu Decoction was slightly decreased. The study showed that Siwu Decoction has the best blood-enriching effect,followed by water decoction and traditional decoction. Alcohol precipitation had the worst effect. Factor analysis can be used for the comprehensive evaluation of blood deficiency mice model,and is a suitable evaluation method for animal model for multi-dimensional multistage complex data analysis. It provides a new model to evaluate the efficacy of multidimensional data in the future.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Animais , Análise Fatorial , Camundongos
19.
Medicine (Baltimore) ; 98(48): e18150, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770256

RESUMO

The current research aimed to investigate the correlation between the effect of Wuzhi soft capsule (WZC) on FK506 concentration and CYP3A5 gene polymorphism in patients with membranous nephropathy (MN).Seventy-five patients with idiopathic MN were enrolled and divided according to the expression of CYP3A5 gene metabolic enzyme into group A (CP3A5 metabolic enzyme function expression types CYP3A5*1/*1 type and CYP3A5*1/*3 type), and group B (non-expression type CYP3A5*3/*3 type). All patients were given oral administration of tacrolimus capsule at the initial dose of 1 mg for twice a day 1 hour before breakfast and dinner. Afterwards, the oral administration of WZC was added at the dose of 0.5 g for 3 times a day within half an hour after 3 meals.The blood concentrations of FK506 in groups A and B were significantly higher than those before administration. Compared with that before administration, the FK506 blood concentration was increased by 3.051 ±â€Š0.774 ng/ml after adding the WZC. Besides, the blood concentrations of FK506 in group A were lower than those in group B before and after administration; meanwhile, the 24 hours total urine protein and the biochemical indexes in both groups displayed no statistically significant difference. Only 1 case of diarrhea was observed, which was relieved after the reduction of tacrolimus.Wuzhi soft capsule can significantly increase the blood concentration of FK506 in MN patients. Moreover, the CYP3A5 genotyping should be considered when WZC is used to increase the blood concentration of FK506.


Assuntos
Citocromo P-450 CYP3A/genética , Medicamentos de Ervas Chinesas , Glomerulonefrite Membranosa , Tacrolimo , Adulto , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/farmacocinética , Cápsulas , Sinergismo Farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacocinética , Feminino , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulonefrite Membranosa/genética , Glomerulonefrite Membranosa/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Farmacogenômicos , Polimorfismo Genético , Medicina de Precisão/métodos , Tacrolimo/administração & dosagem , Tacrolimo/farmacocinética
20.
Molecules ; 24(19)2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31597294

RESUMO

Doxorubicin (DOX) is an effective anti-tumor drug widely used in clinics. Hernandezine (HER), isolated from a Chinese medicinal herb, has a selective inhibitory effect on DOX multidrug resistance, making DOX more effective in treating cancer. The aim of this study was to investigate the effect of the interaction of HER and DOX on pharmacokinetics. Male Sparague-Dawley rats were randomly divided into three groups: a single DOX group, a single HER group, and a combination group. Plasma concentrations of DOX and HER were determined by the LC-MS/MS method at specified time points after administration, and the main pharmacokinetic parameters were estimated. The results showed that there were significant differences in the Cmax and AUC0-∞ of DOX in the single drug group and combined drug group, indicating that HER could improve the absorption of DOX. However, DOX in combination, in turn, reduced the free drug concentration of HER, possibly because DOX enhanced the HER drug-protein binding effect. The results could be used as clinical guidance for DOX and HER to avoid adverse reactions.


Assuntos
Benzilisoquinolinas/farmacocinética , Cromatografia Líquida , Doxorrubicina/farmacocinética , Interações de Medicamentos , Medicamentos de Ervas Chinesas/farmacocinética , Espectrometria de Massas em Tandem , Limite de Detecção , Estrutura Molecular
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