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1.
Mediators Inflamm ; 2021: 6699560, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33505216

RESUMO

Licorice extract is a Chinese herbal medication most often used as a demulcent or elixir. The extract usually consists of many components but the key ingredients are glycyrrhizic (GL) and glycyrrhetinic acid (GA). GL and GA function as potent antioxidants, anti-inflammatory, antiviral, antitumor agents, and immuneregulators. GL and GA have potent activities against hepatitis A, B, and C viruses, human immunodeficiency virus type 1, vesicular stomatitis virus, herpes simplex virus, influenza A, severe acute respiratory syndrome-related coronavirus, respiratory syncytial virus, vaccinia virus, and arboviruses. Also, GA was observed to be of therapeutic valve in human enterovirus 71, which was recognized as the utmost regular virus responsible for hand, foot, and mouth disease. The anti-inflammatory mechanism of GL and GA is realized via cytokines like interferon-γ, tumor necrotizing factor-α, interleukin- (IL-) 1ß, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, and IL-17. They also modulate anti-inflammatory mechanisms like intercellular cell adhesion molecule 1 and P-selectin, enzymes like inducible nitric oxide synthase (iNOS), and transcription factors such as nuclear factor-kappa B, signal transducer and activator of transcription- (STAT-) 3, and STAT-6. Furthermore, DCs treated with GL were capable of influencing T-cell differentiation toward Th1 subset. Moreover, GA is capable of blocking prostaglandin-E2 synthesis via blockade of cyclooxygenase- (COX-) 2 resulting in concurrent augmentation nitric oxide production through the enhancement of iNOS2 mRNA secretion in Leishmania-infected macrophages. GA is capable of inhibiting toll-like receptors as well as high-mobility group box 1.


Assuntos
Anti-Inflamatórios/farmacocinética , Ácido Glicirretínico/farmacocinética , Ácido Glicirrízico/farmacocinética , Fatores Imunológicos/farmacocinética , Animais , Citocinas/metabolismo , Medicamentos de Ervas Chinesas/farmacocinética , Glycyrrhiza/química , Humanos , Inflamação , Interferons/metabolismo , Interleucinas/metabolismo , Leishmania/metabolismo , Sistema de Sinalização das MAP Quinases , Macrófagos/metabolismo , Macrófagos/parasitologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Prostaglandinas/metabolismo , RNA Mensageiro/metabolismo , Células Th1/citologia , Receptores Toll-Like/metabolismo
2.
Xenobiotica ; 51(3): 345-354, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33332226

RESUMO

Abstracts Zhenwu Tang (ZWT) is a traditional Chinese medicine that is primarily composed of Radix Aconiti Lateralis Praeparata (FZ) and diterpenoid alkaloids are believed to be the pharmacologically active compounds of ZWT. In this study, the pharmacokinetic profiles of hypaconitine, mesaconitine, aconitine, benzoylmesaconitine, benzoylaconitine, and benzoylhypacoitine were assessed in rats following intragastric ZWT administration. Furthermore, differences in the pharmacokinetic profiles of these six alkaloids were assessed as a function of rat sex and the administration of ZWT or FZ extracts to these animals. Plasma levels of these alkaloids were quantified via HPLC-MS/MS. Significant differences in key pharmacokinetic parameters were observed when comparing rats administered FZ or ZWT. Relative to FZ extract treatment, ZWT administration was associated with Cmax and AUC0-∞ values of benzoylmesaconitine that were about 3.5 and 5.5 times higher. Considerable variations in hypaconitine pharmacokinetic parameters were also revealed between female and male rats. The Cmax and AUC0-∞ of hypaconitine were about 2.5- and 2.7-fold elevated in female rats in comparison with male rats. These results suggested that the other compounds within ZWT can enhance the absorption of benzoylmesaconitine, while hypaconitine exhibits higher bioavailability in female rats, as compared with male rats.


Assuntos
Aconitum/química , Alcaloides/farmacocinética , Diterpenos/farmacocinética , Medicamentos de Ervas Chinesas/farmacocinética , Animais , Cromatografia Líquida de Alta Pressão , Feminino , Masculino , Ratos , Espectrometria de Massas em Tandem
3.
Chin J Nat Med ; 18(12): 941-951, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33357725

RESUMO

As a representative drug for the treatment of severe community-acquired pneumonia and sepsis, Xuebijing (XBJ) injection is also one of the recommended drugs for the prevention and treatment of coronavirus disease 2019 (COVID-19), but its treatment mechanism for COVID-19 is still unclear. Therefore, this study aims to explore the potential mechanism of XBJ injection in the treatment of COVID-19 employing network pharmacology and molecular docking methods. The corresponding target genes of 45 main active ingredients in XBJ injection and COVID-19 were obtained by using multiple database retrieval and literature mining. 102 overlapping targets of them were screened as the core targets for analysis. Then built the PPI network, TCM-compound-target-disease, and disease-target-pathway networks with the help of Cytoscape 3.6.1 software. After that, utilized DAVID to perform gene ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to predict the action mechanism of overlapping targets. Finally, by applying molecular docking technology, all compounds were docked with COVID-19 3 CL protease(3CLpro), spike protein (S protein), and angiotensin-converting enzyme II (ACE2). The results indicated that quercetin, luteolin, apigenin and other compounds in XBJ injection could affect TNF, MAPK1, IL6 and other overlapping targets. Meanwhile, anhydrosafflor yellow B (AHSYB), salvianolic acid B (SAB), and rutin could combine with COVID-19 crucial proteins, and then played the role of anti-inflammatory, antiviral and immune response to treat COVID-19. This study revealed the multiple active components, multiple targets, and multiple pathways of XBJ injection in the treatment of COVID-19, which provided a new perspective for the study of the mechanism of traditional Chinese medicine (TCM) in the treatment of COVID-19.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa/métodos , Simulação de Acoplamento Molecular/métodos , Transdução de Sinais/efeitos dos fármacos , /metabolismo , Disponibilidade Biológica , /metabolismo , /metabolismo , Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Mapeamento de Interação de Proteínas/métodos , /fisiologia , Glicoproteína da Espícula de Coronavírus/metabolismo
4.
Ecotoxicol Environ Saf ; 205: 111342, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32971455

RESUMO

Radix aconiti lateralis (Fuzi) is widely used in China as a traditional Chinese medicine for the treatment of asthenia, pain and inflammation. However, its toxic alkaloids often lead to adverse reactions. Currently, most of the toxicity studies on Fuzi are focused on the heart and nervous system, and more comprehensive toxicity studies are needed. In this study, based on the previous reports of Fuzi hepatotoxicity, serum pharmacochemistry and network toxicology were used to screen the potential toxic components of Heishunpian(HSP), a processed product of Fuzi, and to explore the possible mechanism of HSP-induced hepatotoxicity. The results obtained are expressed based on the toxicological evidence chain (TEC). It was found that 22 potential toxic components screened can affect Th17 cell differentiation, Jak-STAT signaling pathway, glutathione metabolism, and other related pathways by regulating AKT1, IL2, F2, GSR, EGFR and other related targets, which induces oxidative stress, metabolic disorders, cell apoptosis, immune response, and excessive release of inflammatory factors, eventually inducing liver damage in rats. This is the first study on HSP-induced hepatotoxicity based on the TEC concept, providing references for further studies on the toxicity mechanism of Fuzi.


Assuntos
Aconitum/química , Alcaloides/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/patologia , Medicamentos de Ervas Chinesas/toxicidade , Modelos Biológicos , Alcaloides/sangue , Alcaloides/isolamento & purificação , Animais , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , China , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacocinética , Masculino , Medicina Tradicional Chinesa , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar
5.
Phytomedicine ; 78: 153313, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32866904

RESUMO

BACKGROUND: Previously, we have investigated the therapeutic mechanism of Qingzao Jiufei Decoction (QZJFD), a Chinese classic prescription, on acute lung injury (ALI), however, which remained to be further clarified together with the underlying efficacy related compounds for quality markers (Q-markers). HYPOTHESIS/PURPOSE: To explore Q-markers of QZJFD on ALI by integrating a stepwise multi-system with 'network pharmacology-metabolomics- pharmacokinetic (PK)/ pharmacodynamic (PD) modeling'. METHODS: First, based on in vitro and in vivo component analysis, a network pharmacology strategy was developed to identify active components and potential action mechanism of QZJFD on ALI. Next, studies of poly-pharmacology and non-targeted metabolomics were used to elaborate efficacy and verify network pharmacology results. Then, a comparative PK study on active components in network pharmacology was developed to profile their dynamic laws in vivo under ALI, suggesting Q-marker candidates. Next, quantified analytes with marked PK variations after modeling were fitted with characteristic endogenous metabolites along drug concentration-efficacy-time curve in a PK-PD modeling to verify and select primary effective compounds. Finally, Q-markers were further chosen based on representativeness among analytes through validity analysis of PK quantitation of primary effective compounds. RESULTS: In virtue of 121 and 33 compounds identified in vitro and in vivo, respectively, 33 absorbed prototype compounds were selected to construct a ternary network of '20 components-47 targets-113 pathways' related to anti-ALI of QZJFD. Predicted mechanism (leukocytes infiltration, cytokines, endogenous metabolism) were successively verified by poly-pharmacology and metabolomics. Next, 18 measurable components were retained from 20 analytes by PK comparison under ALI. Then, 15 primary effective compounds from 18 PK markers were further selected by PK-PD analysis. Finally, 9 representative Q-markers from 15 primary effective compounds attributed to principal (chlorogenic acid), ministerial (methylophiopogonanone A, methylophiopogonanone B), adjuvant (sesamin, ursolic acid, amygdalin), conductant drugs (liquiritin apioside, liquiritigenin and isoliquiritin) in QZJFD, were recognized by substitutability and relevance of plasmatic concentration at various time points. CONCLUSION: 9 Q-markers for QZJFD on ALI were identified by a stepwise integration strategy, moreover, which was a powerful tool for screening Q-makers involved with the therapeutic action of traditional Chinese medicine (TCM) prescription and promoting the process of TCM modernization and scientification.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Biomarcadores Farmacológicos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Lesão Pulmonar Aguda/sangue , Lesão Pulmonar Aguda/metabolismo , Administração Oral , Amigdalina/sangue , Animais , Disponibilidade Biológica , Biomarcadores Farmacológicos/análise , Biomarcadores Farmacológicos/metabolismo , Chalcona/análogos & derivados , Chalcona/sangue , Ácido Clorogênico/sangue , Dioxóis/sangue , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacocinética , Flavanonas/sangue , Glucosídeos/sangue , Lignanas/sangue , Masculino , Metabolômica/métodos , Ratos Wistar , Triterpenos/sangue
6.
Phytomedicine ; 72: 153236, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32464544

RESUMO

BACKGROUND: Intestinal obstruction (IO) is a kind of acute abdomen with high morbidity and mortality. Patients suffer from poor quality of life and tremendous financial pressure. Da-Cheng-Qi decoction (DCQD), a classical purgation prescription, has clinically been proven to be an effective treatment for IO. PURPOSE: Network pharmacology integrated with bioactive equivalence assessment was used to discover the quality marker (Q-marker) of DCQD against IO. METHODS: As there is hardly any targets recorded in database, thus the collection of IO targets was conducted by searching those of alternative diseases which have similar pathological symptoms with IO. In order to improve the reliability of the obtained targets, IO metabolomics data was introduced. Active compounds combination (ACC) was focused as potential Q-markers via component-target network analysis and function query from the identified components corresponding to the common targets. Bioequivalence between ACC and DCQD was assessed from the aspects of intestine motility (somatostatin secretion), inflammation (IL-6 secretion) and injury (wound healing assay) in vitro and was further validated in ileus rat model. PPI network analysis of core targets followed by gene pedigree classification and experimental validation confirmed the potential intervention pathway. RESULTS: A combination of 11 ingredients, including emodin, physcion, aloe-emodin, rhein, chrysophanol, gallic acid, magnolol, honokiol, naringenin, tangeretin, and nobiletin was finally confirmed bioequivalence with DQCD to some extent and could serve as Q-markers for DCQD to attenuate IO. PI3K/AKT was verified as a possible affected pathway that DCQD exerted the effectiveness against IO. CONCLUSION: For the disease with few recorded targets, searching those of alternative diseases which have similar pathological symptoms could be a feasible and effective approach. The proposed network pharmacology integrated bioactive equivalence evaluation paradigm is efficient to discover Q-marker of herbal formulae.


Assuntos
Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinética , Obstrução Intestinal/tratamento farmacológico , Algoritmos , Animais , Antraquinonas/análise , Antraquinonas/farmacocinética , Biomarcadores Farmacológicos/análise , Compostos de Bifenilo/análise , Compostos de Bifenilo/farmacocinética , Mineração de Dados , Flavanonas/análise , Flavanonas/farmacocinética , Células HT29 , Humanos , Lignanas/análise , Lignanas/farmacocinética , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Equivalência Terapêutica
7.
Xenobiotica ; 50(11): 1323-1331, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32369406

RESUMO

The compound 20(S),25-epoxydammarane-3ß,12ß,24α-triol (24-hydroxy-panaxadiol or 24-OH-PD), isolated from the red Panax ginseng CA Meyer possesses anticancer activity. Our aim was to study the pharmacokinetic characteristics of 24-OH-PD, which is essential for pre-clinical research during the development of new drugs. In this study, a simple and sensitive ultra-performance liquid chromatography-mass spectrometry (LC-MS/MS) method was established and used for studying the pharmacokinetics, in vitro protein binding, tissue distribution, and elimination profiles of 24-OH-PD in rats. 24-OH-PD was characterized by linear pharmacokinetics in the dose range of 2.5-10 mg/kg and had relatively longer half-life (4.82-5.45 h) than the other ginsenosides. It had a wide tissue distribution profile in rats and was primarily distributed in the lung. Within 96 h of intravenous administration, 13.84% of 24-OH-PD was excreted out via feces and 0.02% via urine in its unchanged form. In conclusion, a simple LC-MS/MS method with high sensitivity and selectivity was established for the quantification of 24-OH-PD.


Assuntos
Antineoplásicos/farmacocinética , Medicamentos de Ervas Chinesas/farmacocinética , Animais , Antineoplásicos/metabolismo , Líquidos Corporais , Medicamentos de Ervas Chinesas/metabolismo , Panax , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
8.
Zhongguo Zhong Yao Za Zhi ; 45(6): 1440-1451, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32281359

RESUMO

The differences of transitional components and metabolic processes of Huatan Jiangqi Capsules(HTJQ) in rats under normal physiological and pathological conditions of COPD were analyzed by UPLC-Q-TOF-MS. The rat COPD model was established by passive smoking and intratracheal instillation of lipopolysaccharide. After the normal and COPD model rats were douched with HTJQ, the blood was collected from hepatic portal vein and the drug-containing serum samples were prepared by methanol precipitation of protein. Then, 10 batches of drug-containing serum samples of HTJQ were prepared and analyzed by UPLC serum fingerprint to evaluate the quality and stability of drug-containing serum samples. UPLC-Q-TOF-MS was used to collect the mass spectrometric information of the transitional components. Twenty-eight transitional components of HTJQ in normal rats and 25 transitional components of HTJQ in COPD model rats were identified by UPLC-Q-TOF-MS. Under pathological and physiological conditions, there were not only the same transitional components in rat serum, but also corresponding differences. Further studies showed that there were also differences in the metabolic process of transitional components between the two conditions. In normal rats, most of the metabolic types of transitional components were phase I reactions. In COPD model rats, phase Ⅰ reactions decreased and phase Ⅱ reactions increased correspondingly. With UPLC-Q-TOF-MS technology, the differences of transitional components and the metabolism process of HTJQ in rats under normal physiological and pathological conditions were analyzed. The results showed that types of transitional components and the activity of some metabolic enzymes would be changed in COPD pathological state, which would affect the metabolic process of bioactive components in vivo. It laid a foundation for further elucidating the metabolic process and pharmacodynamic substance basis of HTJQ.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Soro/química , Animais , Cápsulas , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Ratos
9.
Zhongguo Zhong Yao Za Zhi ; 45(1): 169-178, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32237427

RESUMO

The study aimed to compare the difference in intestinal absorption of the components of Gegen Qinlian Decoction between normal rats and those with large intestinal damp-heat syndrome in the pathological state, in order to explore the rational application of Gegen Qinlian Decoction in the treatment of large intestinal damp-heat syndrome. Puerarin, daidzin, liquiritin, scutellarin, baicalin, wogonoside, coptisine, jatrorrhizine, berberine and palmatine were used as the detection indexes in the in vitro everted gut sacs absorption experiment. The cumulative absorption amount(Q/µg) and the absorption rate(K_a) of each component in each intestine segment were calculated and compared. It was found that the absorption of each component in different intestinal segments were linear absorption, with R~2 greater than 0.9, which conformed to the zero-order absorption rate. There were differences between normal rats and model rats in the absorption of the components in Gegen Qinlian Decoction with the same concentration. Intestinal absorption of most components of Gegen Qinlian Decoction in the model of large intestinal damp-heat syndrome increased to some extent. The components of Gegen Qinlian Decoction with the concentration of 200 g·L~(-1) had the highest absorption in the jejunum of the model rats, and the absorption in the ileum, duodenum and colon successively decreased except daidzin and baicalin. In terms of the absorption rate constant, the absorption in the duodenum and jejunum were significantly increased(P<0.01) compared with normal rats, and the absorption in the ileum was significantly decreased(P<0.01) compared with normal rats. In addition, the absorption of puerarin, daidzin, glycyrrhizin, coptisine and berberine increased selectivity in the colon. Therefore, pathological model animals were recommended in the study of the components relating to absorption effect, in order to really lay a research foundation for the symptomatic treatment of large intestinal damp-heat syndrome.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Absorção Intestinal , Animais , Modelos Animais de Doenças , Ácido Glicirrízico , Medicina Tradicional Chinesa , Ratos
10.
Zhongguo Zhong Yao Za Zhi ; 45(1): 179-187, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32237428

RESUMO

This study is to study the absorption properties of different particle size of Gastrodiae Rhizoma powder in rats. In vivo circulation pass perfusion model combined with ultra high performance liquid chromatography-mass spectrometry(UPLC-MS/MS) method was used to determine the cumulative absorption of each component in different particle size of Gastrodiae Rhizoma powder, and the effect of different particle size, different concentrations, different intestine segments and bile on the intestine absorption of gastrodin and other compositions in Gastrodiae Rhizoma powder was investigated to illuminate the absorption properties and compare the absorption difference of gastrodin and other compositions in Gastrodiae Rhizoma powder in different particle size. The results showed that the absorption of gastrodin in each intestinal segment has no significant difference, pointing out that gastrodin may be passive absorption and the absorption of barrison glycosides may be active absorption; the absorption of gastrodin in ultrafine powder was better than that of common powder and superfine powder of Gastrodiae Rhizoma; the absorption of these barrison glycosides was good in ultrafine powder of Gastrodiae Rhizoma under the high concentration. However, an appropriate degree of superfine grinding can promote the absorption of active ingredients of Gastrodiae Rhizoma. This test can provide information for the deep development of Gastrodiae Rhizoma.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Gastrodia , Absorção Intestinal , Animais , Cromatografia Líquida de Alta Pressão , Tamanho da Partícula , Pós , Ratos , Espectrometria de Massas em Tandem
11.
Zhongguo Zhong Yao Za Zhi ; 45(3): 645-654, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32237525

RESUMO

A sensitive and specific ultra-performance liquid chromatography-mass spectrometry(UPLC-MS/MS) method was deve-loped for analysis of rutaecarpine(Ru), evodiamine(Ev), rutaevine(Rv), limonin(Li), ginsendside Rb_1(Rb_1), ginsendside Re(Re) in rat plasma and brain tissues of nitroglycerin-induced migraine rats. Male healthy Sprague-Dawley(SD) rats were orally given multiple dose of optimized(OS) and un-optimized Wuzhuyu Decoction(UNOS), and their blood samples and brainstem were collected at different time points after injection of nitroglycerin(10 mg·kg~(-1)) into the frontal region. The drug concentrations of the 6 analytes in plasma and brainstem were determined by UPLC-MS/MS method. Subsequently, the main pharmacokinetics parameters of plasma were calculated by using Phoenix WinNolin 5.2.1 software. The methodological test showed that all of analytes in both plasma and brainstem homogenate exhibited a good linearity within the concentration range(r>0.994 7). The intra-day and inter-day accuracy, precision, matrix effect, stability of the investigated components meet the requirements for biopharmaceutical analysis. The developed method was successfully applied in pharmacokinetic studies on abovementioned ingredients in rat plasma and brain stem. The plasma pharmacokinetic parameters of active ingredients in two different Wuzhuyu Decoction group were compared, it was found that Rb_1 had higher t_(1/2), T_(max), C_(max), AUC_(0-24 h) and AUC_(0-∞ )in OS group. Meanwhile, Ev had higher t_(1/2) and T_(max) but lower C_(max), AUC_(0-24 h) and AUC_(0-∞), Ru has higher t_(1/2 )but lower C_(max), AUC_(0-24 h) and AUC_(0-∞ )in OS group. The brain tissue distribution of each component were compared between the two groups, the component with higher content in OS, such as Ru at 30 min and 2 h after administration, Ev at 30 min, Rb_1 at 30 min and Rb_1 at 2 h after administration have lower brain tissue distribution than those in UNOS group, while the component with higher content in UNOS, such as Rv at 30 min, 2 h and 12 h after administration had higher brain tissue distribution than those in OS group.


Assuntos
Transtornos de Enxaqueca/tratamento farmacológico , Administração Oral , Animais , Encéfalo/efeitos dos fármacos , Química Encefálica , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/uso terapêutico , Masculino , Transtornos de Enxaqueca/induzido quimicamente , Nitroglicerina , Plasma/química , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem
12.
Zhongguo Zhong Yao Za Zhi ; 45(3): 655-663, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32237526

RESUMO

To investigate the antipyretic effect of active components of Mahuang Decoction in febrile rats, and explore its correlation with pharmacokinetics at different time points. The feverished rat models were induced by dry yeast, and intragastrically administered with the effective components of Mahuang Decoction with different orthogonal compatibility ratios. At different time points after administration, body temperature was measured; blood was taken from orbital vena plexus, and the contents of interleukin-6(IL-6), interleukin-1ß(IL-1ß), and tumor necrosis factor-α(TNF-α) in rat serum were determined with the kits. Combined with the pharmacokinetic data of the seven effective components in Mahuang Decoction, PK-PD(pharmacokinetics-pharmacodynamics) data fitting was conducted by using the analysis method of non-atrioventricular model, and then the pharmacodynamic parameters were calculated to determine the optimal binding model. The results showed that the effective components of Mahuang Decoction inhibited the release of heat-causing factors IL-6, IL-1ß and TNF-α, and reduced the increase of body temperature. There was a significant lag between drug effect and blood drug concentration, which was consistent with Sigmoid-E_(max) model. The model fitting value showed a good correlation with mea-sured data, which could be used to evaluate and predict the correlation between PK and PD in Mahuang Decoction, and further applied to the multiple-indicator and multiple-effect study of PK-PD in other compound traditional Chinese medicines.


Assuntos
Antipiréticos/uso terapêutico , Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/uso terapêutico , Ephedra sinica/química , Febre/tratamento farmacológico , Animais , Interleucina-1beta/sangue , Interleucina-6/sangue , Medicina Tradicional Chinesa , Ratos , Fator de Necrose Tumoral alfa/sangue
13.
Med Sci Monit ; 26: e919360, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32241963

RESUMO

BACKGROUND This study aimed to undertake a network pharmacology analysis to identify the active compounds of the herbal extract Christina Loosestrife, or Lysimachia Christinae (Jin Qian Cao), in the treatment of nephrolithiasis. MATERIAL AND METHODS The active components of Christina Loosestrife were identified from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and analysis platform and the online Taiwan TCM database. The potentially active compounds were screened based on their parenteral bioavailability identified from the TCMSP database. The PharmMapper integrated pharmacophore matching platform was used for target identification of active compounds in nephrolithiasis. The identified active compounds were validated by molecular docking using the systemsDock network pharmacology website. Biological functions and pathway outcomes of effective targets were analyzed using the Metascape gene annotation resource. The results were used to construct the pharmacological networks, which were visualized and integrated using Cytoscape software. RESULTS There were 16 active compounds of Christina Loosestrife and 11 nephrolithiasis-associated targets that were obtained. Functional enrichment analysis showed that Christina Loosestrife might exert its therapeutic effects by regulating pathways that included purine salvage, interleukin-4 (IL-4) and IL-13 signaling, and neutrophil degranulation. CONCLUSIONS Network pharmacology analysis of the herbal extract, Christina Loosestrife, identified multiple active compounds, targets, and pathways involved in the effects on nephrolithiasis.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Cálculos Renais/tratamento farmacológico , Lythrum/química , Primulaceae/química , Disponibilidade Biológica , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Medicina Tradicional Chinesa/métodos , Simulação de Acoplamento Molecular , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento
14.
Artigo em Inglês | MEDLINE | ID: mdl-32163901

RESUMO

In recent years, depression occurs frequently. Given the long duration of the disease and the high risk of recurrence, the treatment of depression requires long-term medication. Zhi-Zi-Hou-Po Decoction (ZZHPD) has been used in clinical treatment of depression and related diseases for many years, and the potential toxic damage caused by its long-term use has gradually emerged. Existing research methods that expose toxicity by a one-time administration of large doses cannot provide a reference for clinical safe drug use. In this study, the potential toxicity of ZZHPD in repeated administration was studied by urinary metabolomics with nondestructive sampling. Based on ultra-high performance liquid chromatography-quadruple-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS) and chemometrics, 33 differential biomarkers, such as 3-hydroxybutyric acid, indole sulfuric acid, hippuric acid and citric acid, were screened and dynamically tracked. The changes of some endogenous substances showed obvious time dependence. Further analysis of these time-dependent components in combination with network pharmacology revealed that the potential hepatotoxicity and nephrotoxicity of ZZHPD were related to the disorders of amino acid metabolism, energy metabolism, lipid metabolism, nucleotide metabolism and gut microflora metabolism pathway. This study can better grasp the occurrence and development of drug toxicity, and provide reference for rational and safe drug use and potential toxicity prevention of ZZHPD.


Assuntos
Antidepressivos/farmacocinética , Medicamentos de Ervas Chinesas/farmacocinética , Iridoides/farmacocinética , Animais , Antidepressivos/efeitos adversos , Antidepressivos/urina , Biomarcadores/urina , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/efeitos adversos , Iridoides/efeitos adversos , Iridoides/urina , Masculino , Metabolômica , Ratos Sprague-Dawley , Transdução de Sinais , Espectrometria de Massas em Tandem
15.
Phytother Res ; 34(8): 1966-1991, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32135035

RESUMO

Z-ligustilide is a natural benzoquinone derivative found in many widely used Chinese herbal medicines such as Angelica sinensis (Oliv.) Diels as well as Ligusticum chuanxiong Hort and so on. It has been used as a part of traditional Chinese medicine and is also present in various Chinese medicine preparations. Pharmacokinetic studies have shown that Z-ligustilide has poor oral bioavailability in rats due to severe first-pass metabolic reactions. New evidence suggests that Z-ligustilide has a wide range of pharmacological properties, including anticancer, antiinflammatory, anti-oxidant as well as neuroprotective activities and so on. The literature discussed is derived from readily accessible papers spanning the early 1970s to the end of March 2019. Information were collected from journals, books, and online searches (Google Scholar, PubMed, Science Direct, Science Citation Index Finder, Springer link, and CNKI). This review intends to provide a comprehensive overview of the pharmacokinetics and pharmacology of Z-ligustilide in recent years, with a focus on its biological properties and mechanisms, which is of great significance for Chinese medicine.


Assuntos
4-Butirolactona/análogos & derivados , Medicamentos de Ervas Chinesas/uso terapêutico , 4-Butirolactona/farmacocinética , 4-Butirolactona/farmacologia , 4-Butirolactona/uso terapêutico , Animais , Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Estrutura Molecular , Ratos
16.
BMC Complement Med Ther ; 20(1): 61, 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32087732

RESUMO

BACKGROUND: Pharmacokinetic interaction is one of the most important indices for the evaluation of the compatibility of herbal medicines. Both Gancao (Glycyrrhizae Radix et Rhizoma) and Huanglian (Coptidis Rhizoma) are commonly used traditional Chinese medicines (TCMs). In this study, the influence of Gancao on the pharmacokinetics of Huanglian was systematically studied by using berberine as a pharmacokinetic marker. METHODS: Extracts of the herbal pieces of Huanglian and the herb pair (Huanglian plus Gancao) were prepared with boiling water. The concentration of berberine in the samples was analyzed using liquid chromatography-mass spectrometry. The total amounts of berberine in all extract samples were compared. Comparative pharmacokinetic studies of Huanglian and the herb pair were conducted in ICR mice. In vitro berberine absorption and efflux were studied using mice gut sacs. The equilibrium solubility of berberine in the extracts was determined. The in vitro dissolution of berberine was comparatively studied using a rotating basket method. RESULTS: Gancao significantly reduced berberine exposure in the portal circulation (425.8 ng·h/mL vs. 270.4 ng·h/mL) and the liver (29,500.8 ng·h/mL vs. 15,422.4 ng·h/mL) of the mice. In addition, Gancao decreased the peak concentration (Cmax) of berberine in the portal circulation (104.3 ng·h/mL vs. 76.5 ng·h/mL) and liver (4926.1 ng·h/mL vs. 2642.8 ng·h/mL) of mice. Significant influences of Gancao on the amount of berberine extracted (32% reduction), the solubility of berberine (34.7% compared with the control group), and dissolution (88.7% vs. 66.1% at 15 min in acid buffer and 68% vs. 51.8% at 15 min in phosphate buffer) were also revealed. Comparative pharmacokinetic studies in ICR mice indicated that the formation of sediment was unfavorable in terms of berberine absorption (345.3 ng·h/mL vs. 119.8 ng·h/mL). CONCLUSIONS: Gancao was able to reduce intestinal absorption and in vivo exposure of berberine in Huanglian via the formation of sediment, which caused reductions in the extracted amount, solubility, and dissolution of berberine.


Assuntos
Berberina/farmacocinética , Medicamentos de Ervas Chinesas/farmacocinética , Extratos Vegetais/farmacocinética , Animais , Cromatografia Líquida , Quimioterapia Combinada , Feminino , Masculino , Espectrometria de Massas , Medicina Tradicional Chinesa , Camundongos Endogâmicos ICR , Raízes de Plantas
17.
Drug Deliv ; 27(1): 248-257, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32003255

RESUMO

Cancer is a kind of malignant diseases that threatens human health and the research application of anti-tumor drug therapeutics is growingly always been focused on. Many new compounds with great anticancer activity were synthesized but cannot be hard to be developed into clinical use due to its poor water solubility. Deoxypodophyllotoxin (DPT) is just an example. We develop lyophilized Deoxypodophyllotoxin (DPT) loaded polymeric micelles using methoxy polyethylene glycol-block-Poly (D, L-lactide) (mPEG-PLA). DPT-PM freeze-dried powder was successfully prepared using optimized formulation. mPEG-PLA was added to hydration media before hydrating as cryoprotectants. The freeze-dried powder exhibited white pie-solid without collapsing, and the particle size of DPT-PM reconstituted with water was about 20-35 nm. The entrapment efficiency of the reconstituted solution was 98%, which shows no differences with the micelles before lyophilization. In-vitro cytotoxicity and cellular uptake studies showed that DPT-PM has a higher degree of cytotoxicity comparing with DPT and mPEG-PLA micelles and uptake of mPEG-PLA was concentration and time-dependent. In vivo characterization of DPT-PM was done for pharmacokinetics behaviors, antitumor activity and safety. The obtained results showed significant improvement in plasma clearance bioavailability (p <0.05) and prolonged blood circulation time comparing with DPT-HP-ß-CD. Moreover, mPEG-PLA micelles had a better degree of anti-tumor efficacy, this was due to better accumulation of mPEG-PLA in tumor cell via enhanced permeability and retention (EPR) effect. Therefore, DPT-PM has great clinical value, and can be expected to be a novel antitumor preparation.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Medicamentos de Ervas Chinesas/administração & dosagem , Nanopartículas , Podofilotoxina/análogos & derivados , Animais , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/farmacologia , Liofilização , Humanos , Masculino , Camundongos , Camundongos Nus , Micelas , Neoplasias/tratamento farmacológico , Tamanho da Partícula , Podofilotoxina/administração & dosagem , Podofilotoxina/farmacocinética , Podofilotoxina/farmacologia , Poliésteres/química , Polietilenoglicóis/química , Fatores de Tempo , Distribuição Tecidual
18.
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 , Canfanos/química , 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
19.
Complement Ther Med ; 48: 102247, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31987250

RESUMO

Danggui Buxue Tang has been used for menopausal women in China for more than 800 years. However, the potential effective ingredients and pathways require further investigation. The main objective of this work was to explore the potential effective ingredients and pathways. The optimal administration time was optimized by detecting the changes of reticulocytes in peripheral blood. Drug-containing serum (DCS) was taken every 30 min after last administration. Because of the different concentration of effective ingredients absorbed into blood at different time, the pharmacodynamic effect is different. Therefore, bone marrow stromal cells as a member of hematopoietic microenvironment were used to evaluate the pharmacodynamics of DCS. Metabolomics was used to detect changes of metabolites (DBT and endogenous metabolites). The correlation of the metabolites and pharmacodynamics was used to identify the metabolites associated with erythropoiesis. After 14 days, the number of reticulocytes in peripheral blood, erythroid-related cells and erythroid progenitor cells in bone marrow in the DBT group were significantly increased. In vitro experiments showed that DCS at different time had different proliferation effects on BMSCs. Metabolomic analysis showed that the concentration of metabolites in DCS at different time was significantly different. The correlation analysis identified 7 DBT metabolites and 15 endogenous metabolites related to erythropoiesis. 15 endogenous metabolites were finally connected to different pathways. Glutamate is a node molecule. 7 potential effective ingredients of DBT were found. DBT promoted erythropoiesis via promoting the metabolism of glutamate and further affect other pathways.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Eritrócitos/efeitos dos fármacos , Eritropoese/efeitos dos fármacos , Metaboloma , Animais , Camundongos , Modelos Animais
20.
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
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