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1.
J Pharm Biomed Anal ; 177: 112837, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31493746

RESUMO

The ambiguity of dose-effect relationship of many traditional Chinese medicines (TCMs) has always influenced their rational use in TCM clinic. Rhubarb, a preferred representative of cathartic TCM, is currently widely used that results in a diversity of its dosage. The aim of this study was to use an integrated metabolomics strategy to simultaneously reveal dose-effect relationship and therapeutic mechanisms of different efficacy of rhubarb in constipation rats. Six doses of rhubarb (0.135, 0.27, 0.81, 1.35, 4.05, and 8.1 g/kg) were examined to elucidate the laxative and fire-purging effects by pathological sections and UPLC-Q-TOF/MSE. The results showed that there existed serious lesions in the stomach and colon of model rats. And conditions were basically improved to some extent in rhubarb-treated groups. Through relative distance calculation based on metabolomics score plots, it suggested that the effective dose threshold (EC20-EC80 range) of rhubarb was from 0.31 to 4.5 g/kg (corresponding to 3.44-50.00 g in the clinic) in rat serum and 0.29-2.1 g/kg (corresponding to 3.22-23.33 g in the clinic) in feces. Then, 33 potential biomarkers were identified in total. Functional pathway analysis revealed that the alterations of these biomarkers were associated with 15 metabolic pathways, mainly including arachidonic acid metabolism, glycerophospholipid metabolism, steroid biosynthesis, primary bile acid biosynthesis and sphingolipid metabolism. Of note, different doses of rhubarb could alleviate endogenous disorders to varying degrees through regulating multiple perturbed pathways to the normal state, which might be in a dose-dependent manner and involved in therapeutic mechanisms. To sum up, integrated serum and fecal metabolomics obtained that rhubarb ranging from 0.31 to 2.1 g/kg is safe and effective for constipation treatment. Also, our findings showed that the robust metabolomics techniques would be promising to be more accurately used in the dose-effect studies of complex TCM, and to clarify syndrome pathogenesis and action mechanisms in Chinese medicine.

2.
J Pharm Biomed Anal ; 177: 112873, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31539711

RESUMO

A rapid, sensitive and convenient analytical method of ultra-performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry (UPLC-QTRAP®/MS2) was proposed for the simultaneous determination of characteristic alkaline and acidic components covering many structure types including alkaloids, phenolic acids, phenylpropanoids and flavonoids in Leonurus japonicus Houtt. (LJ). The proposed method was first reported and validated by assessing the matrix effects, linearity, limit of detections, limit of quantifications, precision, repeatability, stability and recovery of target components. The developed UPLC-QTRAP®/MS2 was successfully applied to simultaneously determine all target compounds in 38 batches of LJ from 11 different producing regions in China and five organs (including root, caulis, branch, flower and leaf) of LJ from the same stand planting base in Jiangsu Province (China). The result showed that LJ in different regions with different geographical position would affect the accumulation of different compounds, and the significant discrepancies of some target compounds were also observed in different organs of LJ due to different biosynthetic pathway and enzymes in different organs. Furthermore, both hierarchical clustering analysis and principal components analysis were performed to classify the 38 batches of LJ samples from different producing regions on the basis of target compounds. As a result, the samples could be mainly clustered into different groups, which were similar with areas classification. Overall, the presented method would be helpful for the comprehensive utilization and development of LJ resources.

3.
J Ethnopharmacol ; 247: 112284, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31604137

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Herb pair, the most fundamental and simplest form of herb compatibility, serves as the basic building block of traditional Chinese medicine formulae. The Danshen-Honghua herb pair (DH), composed of Salviae Miltiorrhizae Radix et Rhizoma (Danshen in Chinese) and Carthami Flos (Honghua in Chinese), has remarkable clinical efficacy to cure cardio-cerebrovascular diseases. This study was designed to investigate the pharmacodynamics of DH in comparison with single herbs and pharmacokinetics of DH relative to Danshen in acute myocardial ischemic injury. MATERIALS AND METHODS: Sixty male Wistar rats were divided into control, model and drug treated groups. The acute myocardial ischemia rat model was induced by administering 85 mg/kg/d isoproterenol (ISO) subcutaneously for two consecutive days. For pharmacodynamic study, histopathological and biochemical analysis were performed to assess the anti-myocardial ischemic effects. While for pharmacokinetic study, a UPLC-MS/MS method was developed for determination of nine main active ingredients, namely danshensu, protocatechuic acid, protocatechualdehyde, caffeic acid, lithospermic acid, rosmarinic acid, salvianolic acid B, salvianolic acid A and salvianolic acid C in rat plasma. RESULTS: The histopathological and biochemical analysis revealed that DH exerted enhanced anti-myocardial ischemic effects against the ISO-induced myocardial ischemia compared with single herbs. The pharmacokinetic study indicated that DH could significantly increase the t1/2z of danshensu, Tmax, AUC0-∞ and MRT0-t of protocatechuic acid in comparison with Danshen alone in normal rats, but more importantly elevate systemic exposure level and prolong t1/2z of protocatechualdehyde, caffeic acid, Tmax of danshensu in acute myocardial ischemia rats. CONCLUSIONS: Our findings demonstrated the greater effects of DH after the compatibility in ISO-induced acute myocardial ischemia rats at pharmacodynamic and pharmacokinetic levels and provided valuable information for clinical application of herb pairs.

4.
Pharmacol Res ; 148: 104453, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31541688

RESUMO

With the development of system biology, traditional Chinese medicine (TCM) is drawing more and more attention nowadays. However, there are still many enigmas behind this ancient medical system because of the arcane theory and complex mechanism of actions. In recent decades, advancements in genome sequencing technologies, bioinformatics and culturomics have led to the groundbreaking characterization of the gut microbiota, a 'forgotten organ', and its role in host health and disease. Notably, gut microbiota has been emerging as a new avenue to understanding TCM. In this review, we will focus on the structure, composition, functionality and metabolites of gut microbiota affected by TCM so as to conversely understand its theory and mechanisms. We will also discuss the potential areas of gut microbiota for exploring Chinese material medica waste, Chinese marine material medica, add-on therapy and personalized precise medication of TCM. The review will conclude with future perspectives and challenges of gut microbiota in TCM intervention.

5.
Molecules ; 24(18)2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31533325

RESUMO

In the present study, a new strategy including the combination of external appearance, chemical detection, and biological analysis was proposed for the comprehensive evaluation of safflowers in different producing areas. Firstly, 40 batches of safflower samples were classified into class I and II based on color measurements and K-means clustering analysis. Secondly, a rapid and sensitive analytical method was developed for simultaneous quantification of 16 chromaticity-related characteristic components (including characteristic components hydroxysafflor yellow A, anhydrosafflor yellow B, safflomin C, and another 13 flavonoid glycosides) in safflowers by ultra-performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry (UPLC-QTRAP®/MS2). The results of the quantification indicate that hydroxysafflor yellow A, anhydrosafflor yellow B, kaempferol, quercetin, and safflomin C had significant differences between the two types of safflower, and class I of safflower had a higher content of hydroxysafflor yellow A, anhydrosafflor yellow B, and safflomin C as the main anti-thrombotic components in safflower. Thirdly, chemometrics methods were employed to illustrate the relationship in multivariate data of color measurements and chromaticity-related characteristic components. As a result, kaempferol-3-O-rutinoside and 6-hydroxykaempferol-3-O-ß-d-glucoside were strongly associated with the color indicators. Finally, anti-thrombotic analysis was used to evaluate activity and verify the suitability of the classification basis of safflower based on the color measurements. It was shown that brighter, redder, yellower, more orange-yellow, and more vivid safflowers divided into class I had a higher content of characteristic components and better anti-thrombotic activity. In summary, the presented strategy has potential for quality evaluation of other flower medicinal materials.

6.
Zhongguo Zhong Yao Za Zhi ; 44(10): 2131-2138, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31355572

RESUMO

The dose-toxicity-effect relationship between licorice combined with rhubarb in purgation was studied. A total of 108 ICR mice were divided into control group,model group,positive group,low,medium and high-dose rhubarb groups,and low,medium and high-dose rhubarb-liquorice decoction group. After 6 days of continuous administration of loperamide hydrochloride,the constipation model of mice was replicated,and each group was given lactulose,different doses of rhubarb and rhubarb-liquorice decoction for 14 days. After administration,the defecation characteristics,blood biochemistry,liver,kidney and colon pathological changes in each group were compared. Based on the objective weight given by factor analysis,the dose-toxicity-effect relationship was comprehensively analyzed by multi-index scoring method. Two common factors were extracted by factor analysis,representing effect and toxicity respectively. The results showed that rhubarb could exert a diarrhea effect at the dosage of 1/2,2 and 8 times of the high limit set forth in the Chinese Pharmacopoeia,increase the defecation volume and the intestinal tract propulsion rate,reduce the time of anal and the oral transmission,and increase the water content of feces. The combination with licorice could alleviate its diarrhea effect,especially at the dosage of 1/2 times of the high limit set forth in the Chinese Pharmacopoeia. However,rhubarb showed obvious hepatic and colon toxicities at the dosage of 2 and 8 times of the high limit set forth in the Chinese Pharmacopoeia,and the combination with licorice could significantly reduce its toxicity. It shows that licorice has a " mediating" effect on rhubarb by alleviating the purgation property and reducing the toxicity.


Assuntos
Catárticos/farmacologia , Glycyrrhiza/química , Extratos Vegetais/farmacologia , Rheum/química , Animais , Colo , Relação Dose-Resposta a Droga , Rim , Fígado , Camundongos , Camundongos Endogâmicos ICR , Testes de Toxicidade
7.
J Ethnopharmacol ; 238: 111868, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-30981706

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Rhei Radix et Rhizoma (rhubarb), as the preferred representative of cathartic drugs of traditional Chinese medicine (TCM), has a long history of medicinal use and multifarious functions that produce a wide range of dosage. In modern times, rhubarb and its prescriptions are not only used to treat common clinical diseases, but also achieve good results in the treatment of acute, dangerous, severe and difficult diseases. However, rhubarb also has an alias called "General", which means that its efficacy is relatively rapid. AIM OF THE STUDY: The present study was conducted to simultaneously elucidate dosage-effect relationship of rhubarb of different efficacy, "Removing accumulation with purgation" (E1) and "Clearing heat and purging fire" (E2), providing reference for the safe and effective usage of rhubarb. MATERIALS AND METHODS: Three-week-old rats were randomly divided into the normal control group (Con.), model group (Mod.) and rhubarb groups with six doses (0.135, 0.27, 0.81, 1.35, 4.05, 8.1 g/kg). We established a constipation model with gastrointestinal accumulated heat induced by dyspepsia, taking defecation characteristics observed by metabolic cages, alvine pushing rate, gastrointestinal hormones in serum, etc., as indicators of E1, and taking TG, Na+-K+-ATPase, inflammatory factors and proteins, etc., as indicators of E2. The factor analytic approach was used to systematically evaluate the two effects and analyze the corresponding dosage-effect relationship. RESULTS: The levels of Gas, AchE, TG, Na+-K+-ATPase, TNF-α, IL-1ß, (p-)NF-κB p65, (p-)p38, (p-)ERK and p-JNK in model rats increased significantly while the levels of defecation, fecal water content, MTL, SS, ET, NTS, VIP, JNK and TLR4 decreased. Compared with the Mod., in rhubarb groups, the increase of faeces, alvine pushing rate, most gastrointestinal hormones, etc., reflected the therapeutic efficacy of E1, and the reduction of TG, Na+-K+-ATPase, expression levels of inflammatory indexes, etc., reflected the impact of E2. After the analysis, the effective threshold dose ranging from 0.67 to 5.37 g/kg (corresponding to 7.44-59.67 g in the clinic) was in the EC20-EC80 range for E1 treatment and from 0.78 to 5.60 g/kg (equivalently clinical 8.67-62.22 g) was for E2 treatment. And the 1.6- and 1.2-fold rhubarb highest dose of Chinese Pharmacopoeia might be the optimal doses for E1 and E2 respectively. In general, however, the concentration of rhubarb liquid for overall efficacy is suggested to be between middle and highest dose of Chinese Pharmacopoeia. CONCLUSION: A constipation model was used to elucidate two main effects of rhubarb, which was consistent with the characteristics of TCM syndrome. In the wide range of rhubarb dosage, low doses might have little or no effect and although high concentrations of rhubarb liquid enhanced curative efficacy, it would also have certain side effects on the body. Therefore, scientific-based experiments and rational analysis by mathematical models could contribute to the safe and effective application of rhubarb in the clinic.


Assuntos
Constipação Intestinal/tratamento farmacológico , Laxantes/farmacologia , Extratos Vegetais/farmacologia , Rheum/química , Animais , Colo/efeitos dos fármacos , Colo/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/metabolismo , Laxantes/química , Masculino , Medicina Tradicional Chinesa , Fitoterapia , Extratos Vegetais/química , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
8.
Oxid Med Cell Longev ; 2019: 8636835, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30911351

RESUMO

Ginkgo ketoester tablets (GT) and donepezil were a clinically used combination for the treatment of Alzheimer's disease (AD). The aim of the study was undertaken to investigate the antiamnesic effects of the two drugs alone and in combination through in vivo models of the Morris water maze along with in vitro antioxidants, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The potential mechanisms were speculated by the activities of acetylcholine (ACh), AChE, superoxide dismutase (SOD), and malondialdehyde (MDA) and the protein expression of brain-derived neurotrophic factor (BDNF) and tyrosine protein kinase B (TrkB). The combination group showed a concentration-dependent inhibition of cholinesterase and antioxidation. As far as its mechanism was concerned, the combination of two drugs exerted excellent effects on oxidative stress, cholinergic pathway damage, and inactivation of the BDNF-TrkB signaling pathway. Additionally, to elucidate the binding mechanism of GT active ingredients into the structure of AChE, the results of molecular docking studies indicated that hydrogen and/or hydrophobic bonds might play an important role in their binding process. Thus, the combination of drugs could treat AD perfectly and further verify the scientific rationality of clinical medication.


Assuntos
Amnésia/tratamento farmacológico , Donepezila/uso terapêutico , Ginkgo biloba/química , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Acetilcolina/metabolismo , Acetilcolinesterase , Amnésia/patologia , Animais , Benzotiazóis/química , Compostos de Bifenilo/química , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Inibidores da Colinesterase/farmacologia , Transtornos Cognitivos/tratamento farmacológico , Donepezila/farmacologia , Quimioterapia Combinada , Ginkgolídeos/química , Ligantes , Malondialdeído/metabolismo , Camundongos Endogâmicos ICR , Simulação de Acoplamento Molecular , Picratos/química , Extratos Vegetais/farmacologia , Receptor trkB/metabolismo , Escopolamina , Ácidos Sulfônicos/química , Superóxido Dismutase/metabolismo , Comprimidos
9.
J Ethnopharmacol ; 235: 227-242, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-30703496

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Danggui buxue Decoction (DBD) has been frequently used to treat with blood deficiency, which consisted of Danggui (DG) and Huangqi (HQ) at a ratio of 1:5. Accumulating evidence showed that blood deficiency in traditional Chinese medicine (TCM) was similar to anemia in modern medicine. AIM OF THE STUDY: The purpose of this study was to explore its therapeutic mechanism of with network pharmacology approach. MATERIALS AND METHODS: We explored the chemical compounds of DBD and used compound ADME screening to identify the potential compounds. Targets for the therapeutic actions of DBD were obtained from the PharmMapper, Swiss, SEA and STITCH. GO analysis and pathway enrichment analysis was performed using the DAVID webserver. Cytoscape was used to visualize the compound-target-pathway network for DBD. The pharmacodynamics and crucial targets were also validated. RESULTS: Thirty-six potential active components in DBD and 49 targets which the active components acted on were identified. 47 KEGG pathways which DBD acted on were also come to light. And then, according to KEGG pathway annotation analysis, only 16 pathways seemed to be related to the blood nourishing effect of DBD, such as PI3K-AKT pathway, and so on. Only 32 targets participated in these 16 pathways and they were acted on by 29 of the 36 active compounds. Whole pharmacodynamic experiments showed that DBD had significant effects to blood loss rats. Furthermore, DBD could promote the up-regulation of hematopoietic and immune related targets and the down-regulation of inflammatory related targets. Significantly, with the results of effective rate, molecular docking and experimental validation, we predicted astragaloside IV in HQ, senkyunolide A and senkyunolide K in DG might be the major contributing compounds to DBD's blood enriching effect. CONCLUSION: In this study, a systematical network pharmacology approach was built. Our results provided a basis for the future study of senkyunolide A and senkyunolide K as the blood enriching compounds in DBD. Furthermore, combined network pharmacology with validation experimental results, the nourishing blood effect of DBD might be manifested by the dual mechanism of enhancing immunity and promoting hematopoiesis.


Assuntos
Células Sanguíneas/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa/métodos , Simulação de Acoplamento Molecular , Animais , Células CACO-2 , Regulação para Baixo/efeitos dos fármacos , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Regulação para Cima/efeitos dos fármacos
10.
J Sep Sci ; 42(6): 1122-1132, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30618086

RESUMO

A rapid and sensitive ultra high performance liquid chromatography coupled to triple quadrupole tandem mass spectrometry method was established and employed to determine 21 nucleosides, nucleobases, and amino acids in 60 samples from different parts of Angelicae Sinensis Radix. The established methods were validated by good linearity (r2  > 0.9937), limits of detection (0.12-77.75 ng/mL), limits of quantitation (0.31-272.13 ng/mL), intra- and interday precisions (RSD ≤ 4.84%, RSD ≤ 6.26%), stability (RSD ≤ 5.92%), repeatability (RSD ≤ 7.14%), recovery (91.4-103.4%), and matrix effects (0.92-1.03). Chemical comparative analysis revealed that the content of total analytes in four parts of Angelicae Sinensis Radix were different, and exhibited the order: Head (14.89 mg/g) > Body (10.15 mg/g) > All (8.22 mg/g) > Tail (6.23 mg/g). Principal component analysis showed that the samples could be classified into four groups in accord with four different parts of Angelicae Sinensis Radix. The results could provide a scientific basis and reference for the quality control of Angelicae Sinensis Radix, and may be conducive to further research on the pharmacological activities of Angelicae Sinensis Radix.


Assuntos
Aminoácidos/análise , Angelica sinensis/química , Nucleosídeos/análise , Cromatografia Líquida de Alta Pressão , Conformação Molecular , Análise de Componente Principal , Controle de Qualidade , Espectrometria de Massas em Tandem
11.
Int J Mol Sci ; 19(10)2018 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-30287737

RESUMO

Sipunculus nudus, an old marine species, has great potential for use as functional seafood due to its various bioactivities. Its potential antithrombotic activity pushed us to isolate the bio-active components bio-guided by tracking fibrinolytic activity. As a result, a novel protease named as SK (the kinase obtained from S. nudus) was obtained, which possessed a molecular weight of 28,003.67 Da and 15 N-terminal amino acid sequences of PFPVPDPFVWDTSFQ. SK exerted inhibitory effects on thrombus formation through improving the coagulation system with dose-effect relationship within a certain range. Furthermore, in most cases SK got obviously better effect than that of urokinase. With the help of untargeted mass spectrometry-based metabolomics profiling, arachidonic acid, sphingolipid, and nicotinate and nicotinamide mechanism pathways were found to be important pathways. They revealed that the effect mechanism of SK on common carotid arterial thrombosis induced by FeCl3 was achieved by inhibiting vessel contraction, platelet aggregation, adhesion, and release, correcting endothelial cell dysfunction and retarding process of thrombus formation. This study demonstrated SK was a promising thrombolytic agent on the basis of its comprehensive activities on thrombosis, and it should get further exploitation and utilization.


Assuntos
Trombose das Artérias Carótidas/tratamento farmacológico , Fibrinolíticos/metabolismo , Proteínas de Helminto/metabolismo , Nematoides/enzimologia , Peptídeo Hidrolases/metabolismo , Animais , Fibrinolíticos/química , Fibrinolíticos/uso terapêutico , Proteínas de Helminto/química , Proteínas de Helminto/uso terapêutico , Masculino , Peptídeo Hidrolases/química , Peptídeo Hidrolases/uso terapêutico , Ratos , Ratos Sprague-Dawley
12.
Front Pharmacol ; 9: 165, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29551975

RESUMO

As a well-known traditional Chinese medicine (TCM) prescription, Xin-Sheng-Hua Granule (XSHG) has been applied in China for more than 30 years to treat postpartum diseases, especially anemia. However, underlying therapeutic mechanisms of XSHG for anemia were still unclear. In this study, plasma metabolomics profiling with UHPLC-QTOF/MS and multivariate data method was firstly analyzed to discover the potential regulation mechanisms of XSHG on anemia rats induced by bleeding from the orbit. Afterward, the compound-target-pathway network of XSHG was constructed by the use of network pharmacology, thus anemia-relevant signaling pathways were dissected. Finally, the crucial targets in the shared pathways of metabolomics and network pharmacology were experimentally validated by ELISA and Western Blot analysis. The results showed that XSHG could exert excellent effects on anemia probably through regulating coenzyme A biosynthesis, sphingolipids metabolism and HIF-1α pathways, which was reflected by the increased levels of EPOR, F2, COASY, as well as the reduced protein expression of HIF-1α, SPHK1, and S1PR1. Our work successfully explained the polypharmcological mechanisms underlying the efficiency of XSHG on treating anemia, and meanwhile, it probed into the potential treatment strategies for anemia from TCM prescription.

13.
Zhongguo Zhong Yao Za Zhi ; 42(15): 3017-3025, 2017 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-29139273

RESUMO

To evaluate the promoting blood circulation and removing blood stasis effects of Danshen-Honghua(DH) herb pair with different preparations (alcohol, 50% alcohol and water) on blood rheology and coagulation functions in acute blood stasis rats, and optimize the best preparation method of DH based on principal component analysis(PCA), hierarchical cluster heatmap analysis and multi-attribute comprehensive index methods. Ice water bath and subcutaneous injection of adrenaline were both used to establish the acute blood stasis rat model. Then the blood stasis rats were administrated intragastrically with DH (alcohol, 50% alcohol and water) extracts. The whole blood viscosity(WBV), plasma viscosity(PV), erythrocyte sedimentation rate(ESR) and haematocrit(HCT) were tested to observe the effects of DH herb pair with different preparations and doses on hemorheology of blood stasis rats; the activated partial thromboplastin time(APTT), thrombin time(TT), prothrombin time(PT), and plasma fibrinogen(FIB) were tested to observe the effects of DH herb pair with different preparations on blood coagulation function and platelet aggregation of blood stasis rats. Then PCA, hierarchical cluster heatmap analysis and multi-attribute comprehensive index methods were all used to comprehensively evaluate the total promoting blood circulation and removing blood stasis effects of DH herb pair with different preparations. The hemorheological indexes and coagulation parameters of model group had significant differences with normal blank group. As compared with the model group, the DH herb pair with different preparations at low, middle and high doses could improve the blood hemorheology indexes and coagulation parameters in acute blood stasis rats with dose-effect relation. Based on the PCA, hierarchical cluster heatmap analysis and multi-attribute comprehensive index methods, the high dose group of 50% alcohol extract had the best effect of promoting blood circulation and removing blood stasis. Under the same dose but different preparations, 50% alcohol DH could obviously improve the hemorheology and blood coagulation function in acute blood stasis rats. These results suggested that DH herb pair with different preparations could obviously ameliorate the abnormality of hemorheology and blood coagulation function in acute blood stasis rats, and the optimized preparation of DH herb pair on promoting blood effects was 50% alcohol extract, providing scientific basis for more effective application of the DH herb pair in modern clinic medicine.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Hemorreologia , Salvia miltiorrhiza/química , Animais , Carthamus tinctorius/química , Fibrinogênio/análise , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Ratos , Tempo de Trombina
14.
Molecules ; 22(10)2017 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-29039793

RESUMO

The compatibility between Danggui (Angelicae Sinensis Radix) and Honghua (Carthami Flos) is a known herb pair, which could activate blood circulation and dissipate blood stasis effects. In this paper, we quantified seven main bio-active components (hydroxysafflor yellow A, caffeic acid, p-coumaric acid, kaempferol-3-O-rutinoside, ferulic acid, 3-n-butylphthalide, and ligustilide) in plasma samples in vivo by UPLC-TQ/MS method and investigatedwhether the pharmacokinetic (PK) behaviors of the seven components could be altered in blood stasis rats after oral administration of the Gui-Hong extracts. It was found that the Cmax and AUC0-t of these components in blood stasis rats had increasing tendency compared with normal rats. Most components in model and normal rats had significant difference in some pharmacokinetic parameters, which indicated that the metabolism enzymes and transporters involved in the metabolism and disposition of these bio-active componentsmay bealtered in blood stasis rats. This study was the first report about the pharmacokinetic investigation between normal and blood stasis rats after oral administrationof Gui-Hong extracts, and these results are important and valuable for better clinical applications of Gui-Hong herb pair and relatedTCM formulae.


Assuntos
Produtos Biológicos/química , Produtos Biológicos/farmacocinética , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinética , Administração Oral , Animais , Produtos Biológicos/administração & dosagem , Biomarcadores , Carthamus tinctorius/química , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Testes Hematológicos , Espectrometria de Massas , Estrutura Molecular , Controle de Qualidade , Ratos , Sensibilidade e Especificidade
15.
J Sep Sci ; 40(17): 3392-3401, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28657142

RESUMO

A sensitive, reliable, and powerful ultra-high performance liquid chromatography coupled to triple quadrupole tandem mass spectrometry method was developed for simultaneous quantification of the 15 main bio-active components including phenolic acids and flavonoids within 13 min for the first time. The proposed method was first reported and validated by good linearity (r2  > 0.9975), limit of detection (1.12-7.01 ng/mL), limit of quantification (3.73-23.37 ng/mL), intra- and inter-day precisions (RSD ≤ 1.92%, RSD ≤ 2.45%), stability (RSD ≤ 5.63%), repeatability (RSD ≤ 4.34%), recovery (96.84-102.12%), and matrix effects (0.92-1.02). The established analytical methodology was successfully applied to comparative analysis of main bio-active components in the herb pair Danshen-Honghua and its single herbs. Compared to the single herb, the content of most flavonoid glycosides was remarkably increased in their herb pair, and main phenolic acids were decreased, conversely. The content changes of the main components in the herb pair supported the synergistic effects on promoting blood circulation and removing blood stasis. The results provide a scientific basis and reference for the quality control of Danshen-Honghua herb pair and the drug interactions based on variation of bio-active components in herb pairs.


Assuntos
Medicamentos de Ervas Chinesas/análise , Salvia miltiorrhiza/química , Carthamus tinctorius/química , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas em Tandem
16.
Artigo em Inglês | MEDLINE | ID: mdl-28499205

RESUMO

Kansui, the root of Euphorbia kansui T.N. Liou ex T.P. Wang (Euphorbiaceae), is a well-known poisonous traditional Chinese medicine (TCM). However, many monographs of TCM indicated that it cannot be co-used with licorice, as kansui-licorice is a typical "eighteen incompatible" medicaments. Our previous studies have indicated that kansui was effective in treating malignant pleural effusion (MPE), and the efficacy could be weakened by the co-use of licorice, even causing serious toxicity at the given ratio. Nevertheless, the actual mechanisms of their dosage-toxicity-efficacy relationship need to be well clarified. The present study aimed to investigate the effect of individual and combined use of kansui and licorice on MPE rats, and explain the underlying mechanisms from a metabolomic perspective. Urine samples were analyzed by ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Partial least-squares discriminate analysis (PLS-DA) models were built to evaluate the interaction between kansui and licorice. Seven potential biomarkers contribute to the separation of model group and control group were tentatively identified. And selenoamino acid metabolism and nicotinate and nicotinamide metabolism with the impact-value 0.31 and 0.24, respectively, were filtered out as the most important metabolic pathways. Kansui and kansui-licorice at a ratio of 4:1 can treat MPE rats by adjusting abnormal metabolic pathways to the normal state, while it may have opposite result with kansui-licorice 1:4. The different influences to the two metabolic pathways may partially explain the dosage-toxicity-efficacy relationship of kansui-licorice with different ratios. The results could offer valuable insights into the compatibility property changes for the two herbs.


Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/metabolismo , Euphorbia/química , Glycyrrhiza/química , Derrame Pleural Maligno/tratamento farmacológico , Derrame Pleural Maligno/metabolismo , Animais , Biomarcadores/urina , Interações de Medicamentos , Medicamentos de Ervas Chinesas/toxicidade , Masculino , Redes e Vias Metabólicas , Metabolômica , Análise Multivariada , Raízes de Plantas/química , Derrame Pleural Maligno/urina , Ratos , Ratos Wistar , Espectrometria de Massas em Tandem
17.
Chin Med ; 12: 36, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29299052

RESUMO

Rhubarb is one of the most ancient, commonly used and important herbs in Chinese medicine. The modern researches of rhubarb clarified the efficacies, ingredients and mechanisms in a more scientific and rigorous way. The main chemical compositions of rhubarb include anthraquinones, anthrones, stilbenes, tannins, polysaccharides etc. These compositions show extensive pharmacological activities including regulating gastrointestinal, anticancer, antimicrobial, hepatoprotective, anti-inflammatory, protecting cardiovascular, cerebrovascular and so on. This paper reviews the recent studies on the active ingredients, pharmacological effects, clinical application and functional mechanism.

18.
J Ethnopharmacol ; 186: 251-256, 2016 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-27084456

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The root of Euphorbia kansui T.P. Wang (Euphorbiaceae), a well-known traditional Chinese medicine (TCM) with certain toxicity, is known as Gan sui (Chinese: ) or kansui. It has been used to treat edema, ascites, asthma, and etc. Licorice is the root of Glycyrrhiza uralensis Fisch. or Glycyrrhiza inflate Bat. or Glycyrrhiza glabra L., Leguminosae. It is a widely used herbal medicine native to southern Europe and parts of Asia as an herbal medicine and natural sweetener. Kansui cannot be co-used with licorice, which is recorded in "eighteen incompatible" medicaments in many monographs of TCM. AIM OF THE STUDY: The present study was conducted to investigate the dosage-toxicity-efficacy relationship of the co-use of kansui and licorice and to explore its regularity of the toxicity and efficacy change. MATERIALS AND METHODS: Malignant pleural effusion rats were used and randomly divided into the normal control group, model group, positive control group (furosemide), kansui group, licorice group, and kansui-licorice groups with different ratios (kansui: licorice: 4:1, 2:1, 1:1, 0.5:1, 0.25:1, 0.1:1). Each group was adopted simultaneously to investigate the characteristic of toxicity and effect by measuring the pleural fluid and urine volumes, serum biochemical indexes, and serum TNF-α, IL-2 and IFN-γ levels. The factor analytic approach was used to analyze the dosage-toxicity-efficacy relationship between kansui and licorice. RESULTS: Two common factors were extracted from 8 indexes concerning toxicity and 5 indexes concerning efficacy. And the total factors related to toxicity (Ft) and efficacy (Fe) were calculated. The curved line of Ft indicated that the toxicity was increased along with the dose increase in licorice. The curved line of Fe indicated that the efficacy was decreased along with the dose increase in licorice. The intersection of these two lines was between the ratios of 2:1 and 1:1, and was deemed the flex point of the dosage-toxicity-efficacy. CONCLUSIONS: Kansui demonstrated a certain efficacy in treating malignant pleural effusion, and the efficacy could be weakened by the co-use of licorice, even causing serious toxicity at the given ratio. The ratio between 2:1 and 1:1 (kansui: licorice) was deemed the flex point of the dosage-toxicity-efficacy of kansui and licorice. The results will be helpful for their better utilization and development.


Assuntos
Euphorbia , Glycyrrhiza , Extratos Vegetais/toxicidade , Extratos Vegetais/uso terapêutico , Derrame Pleural Maligno/tratamento farmacológico , Animais , Relação Dose-Resposta a Droga , Interações de Medicamentos , Análise Fatorial , Interferon gama/sangue , Interleucina-2/sangue , Masculino , Fitoterapia/efeitos adversos , Raízes de Plantas , Derrame Pleural Maligno/sangue , Ratos Wistar , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangue
19.
Chin J Nat Med ; 12(9): 705-11, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25263985

RESUMO

Ultraperformance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and the Metabolynx™ software, combined with mass defect filtering, were applied to identity the metabolites of quercetin-3-O-ß-D-gluco-pyranosyl-(4→1)-α-L-rhamnoside (QGR) in rats after intravenous administration. MS(E) was used for simultaneous acquisition of precursor ion information and fragment ion data at high and low collision energy in one analytical run, which facilitated the rapid structural characterization of eight metabolites in rat plasma, urine and bile. The results indicated that methylation and glucuronidation were the major metabolic pathways of QGR in vivo. The present study provided important information about the metabolism of QGR which will be useful for fully understanding the mechanism of action of this compound. Furthermore, this work demonstrated the potential of the UPLC-Q-TOF/MS approach using Metabolynx for rapid and automated research of the metabolites of natural products.


Assuntos
Ginkgo biloba/química , Extratos Vegetais/metabolismo , Quercetina/metabolismo , Administração Intravenosa , Animais , Cromatografia Líquida de Alta Pressão , Masculino , Espectrometria de Massas/métodos , Quercetina/análogos & derivados , Ratos Sprague-Dawley
20.
Guang Pu Xue Yu Guang Pu Fen Xi ; 33(3): 808-12, 2013 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-23705459

RESUMO

Abstract Inorganic elements were determined by ICP-AES using microwave digestion, and principal components analysis(PCA) was used for analysis. The result showed that ginkgo biloba leaves contained more than 22 inorganic elements, Fe, Zn, Cu, Mn, Cr, Co, Ni, Sr, B, Si and Ni were essential trace elements, and Ca, P, K% Na and Mg were essential macro elements. PCA with seven factors (F1, F2, F3, F4, F5, F6, F7) selected could be used to evaluate the quality of ginkgo biloba leaves. The function was following F=0.230 17F1+0.122 39F2+0.079 67F3+0.078 97F4+0.065 25F5+0.062 03F6+0.056 71F7. The samples from Taixing, Shijiazhuang and Taian was the top three which indicated the quality in those cultivation sources was better based on inorganic elements. All the results will provide good basis for comprehensive utilization of ginkgo biloba leaves, especially the leaves from fruit cultivars.


Assuntos
Ginkgo biloba/química , Compostos Inorgânicos/análise , Folhas de Planta/química , Espectrofotometria Atômica/métodos , Oligoelementos/análise , Micro-Ondas , Análise de Componente Principal
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