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1.
J Chromatogr A ; : 460850, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31983414

RESUMO

In-source fragmentation of ginsenosides in the positive ESI mode (pISF-G) frequently occurs, which results in little fragment information useful for the structural elucidation. We are aimed to unveil the genesic mechanism and explore its potential significance in quality control of Ginseng and the related compound formulae. By applying six high-resolution mass spectrometers from Agilent, Waters, and Thermo Fisher, we could primarily demonstrate the susceptibility of pISF-G. The ion clusters in the positive full-scan MS1 spectra were generated from the protonated sapogenins by successive elimination of H2O, and showed specificity for ginsenoside classification. Selective ion monitoring (SIM) of the sapogenin product ions could delineate group-target ginsenoside profiles from Ginseng. A high-selectivity characteristic chromatogram (CC) was elaborated for Ginseng, on the Vion™ IMS-QTOF mass spectrometer by IM (ion mobility) separation and quadrupole filtering of four sapogenin fragments (m/z 407.37/CCS 206.24 Å2; m/z 423.36/CCS 211.26 Å2; m/z 439.36/CCS 209.60 Å2; m/z 457.37/CCS 217.81 Å2). Chemometric analysis, based on the CC data of seven Ginseng drugs (P. ginseng, P. quinquefolius, P. notoginseng, Red ginseng, leaf of P. ginseng, P. japonicus, and P. japonicus var. major), disclosed 35 marker compounds. We could readily discriminate among P. ginseng, P. quinquefolius, and P. notoginseng, in 15 different compound formulae by identifying these marker compounds on both the Vion IMS-QTOF and QTrap 4500 mass spectrometers. Conclusively, SIM of the pISF-G sapogenin product ions renders a new concept of CC enabling the group-target profiling of ginsenosides and authentication of Ginseng and the related compound formulae.

2.
Int J Biol Macromol ; 144: 1004-1012, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31715236

RESUMO

Alzheimer's disease (AD) is the most common degenerative disease of the central nervous system. It is associated with abnormal accumulation of amyloid-ß (Aß) plaques, impaired neurogenesis, and damaged cognitive functions. We have known for a long time that natural compounds and their derivatives have gained increasing attention in AD drug research due to their multiple effects and inherently enormous chemicals. In this study, we will demonstrate that polysaccharides from L. barbarum (LBP1), a traditional natural compound, can reduce Aß level and improve the cognitive functions in APP/PS1 transgenic mouse. LBP1 can enhance neurogenesis as indicated by BrdU/NeuN double labeling. Furthermore, it can restore synaptic dysfunction at hippocampus CA3-CA1 pathway. Additionally, in vitro cell assay indicates that LBP1 may affect Aß processing. In conclusion, our study indicates that LBP1 might be a potential therapeutic agent for the treatment of AD against multiple targets that include synaptic plasticity, Aß pathology and neuropathology.

3.
J Pharm Biomed Anal ; 177: 112813, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31472326

RESUMO

Differentiated composition in precursor ions for different subclasses of ginsenosides in the negative electrospray-ionization mode has been reported, which lays a foundation for the sorted and untargeted identification of ginsenosides. Carboxyl-free ginsenosides simultaneously from Panax ginseng, P. quinquefolius, and P. notoginseng, were comprehensively characterized and statistically compared. A neutral loss/product ion scan (NL-PIS) incorporated untargeted profiling approach, coupled to ultra-high performance liquid chromatography, was developed on a linear ion-trap/Orbitrap mass spectrometer for characterizing carboxyl-free ginsenosides. It incorporated in-source fragmentation (ISF) full scan-MS1, mass tag-MS2, and product ion scan-MS3. Sixty batches of ginseng samples were analyzed by metabolomics workflows for the discovery of ginsenoside markers. Using formic acid (FA) as the additive, carboxyl-free ginsenosides (protopanaxadiol-type, protopanaxatriol-type, and octillol-type) gave predominant FA-adducts, while rich deprotonated molecules were observed for carboxyl-containing ginsenosides (oleanolic acid-type and malonylated) when source-induced dissociation (SID) was set at 0 V. Based on the NL transition [M+FA‒H]- > [M-H]- and the characteristic sapogenin product ions, a NL-PIS approach was established. It took advantage of the efficient full-information acquisition of ISF-MS1 (SID: 50 V), the high specificity of mass tag (NL: 46.0055 Da)-induced MS2 fragmentation, and the substructure fragmentation of product ion scan-MS3. We could characterize 216 carboxyl-free ginsenosides, and 21 thereof were potentially diagnostic for the species differentiation. Conclusively, sorted and untargeted characterization of the carboxyl-free ginsenosides was achieved by the established NL-PIS approach. In contrast to the conventional NL or PIS-based survey scan strategies, the high-accuracy MSn data obtained can enable more reliable identification of ginsenosides.

4.
J Ethnopharmacol ; 251: 112490, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31884035

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Venenum Bufonis, a product of the secretions of Bufo gargarizans Cantor or B. melanostictus Schneider, possessed an array of pharmacological activities, such as cardiotonic, anti-tumor, antinociceptive, anti-inflammatory, anesthetic and antimicrobial activities. However, there were few efficient methods for quality evaluation of Venenum Bufonis medicinal materials and its related Chinese patent medicines. AIM OF THE STUDY: To establish an effective method for quality assessment of crude drugs and Chinese proprietary medicines of Venenum Bufonis, and explore the relationship of primary compounds - target - pathway - disease through a series of network databases. MATERIALS AND METHODS: An ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-QqQ-MS/MS) method was developed and validated to simultaneously determine 14 bufadienolides for quantitative analysis of 71 batches of crude drugs and 20 kinds of Chinese patent medicines of Venenum Bufonis. Multiple reaction monitoring with good specificity and accuracy was applied to monitor the 14 bufadienolides in positive mode. RESULTS: The methodology was validated with good specificity, precision, stability, repeatability and recovery. The low limits of quantification were in the range of 0.1-2.7 ng/mL. The relative standard deviation values for intra- and inter-day precisions ranged from 0.98% to 6.3% and from 2.39% to 6.76%, respectively. The recovery was varied from 87.78% to 110.57% for crude drugs and 88.32%-100.96% for Chinese proprietary medicine (Shexiang Baoxin Pill). The contents of 14 analytes in 71 batches of crude drugs and 20 sorts of Chinese proprietary medicines were procured, the results showed that the contents of crude drugs collected from the market exhibited great variations. Furthermore, 13 batches of crude drugs were identified as counterfeit with no bufadienolides detected. In addition, the total contents of bufadienolides in the same drug showed great difference among products from various manufacturers or brands. Subsequently, 9 bufadienolides with the higher contents were applied to screen the anti-tumor effect by network pharmacology, and 8 pathways which had prior correlation with bufadienolides were disclosed. CONCLUSION: This method could be used for quality assessment of crude drugs and Chinese patent medicines of Venenum Bufonis, and the data could be served as the fundamental basis for drug research and development of Venenum Bufonis.

5.
J Sep Sci ; 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31858716

RESUMO

Source authentication of herbal medicines was essential for ensuring their safety, efficacy and quality consistency, especially those with multiple botanical origins. This study proposed a metabolomics strategy for species discrimination and source recognition. Uncariae Rammulus Cum Uncis, officially stipulating the stems with hooks of five Uncaria species as its origins, was taken as a case study. Firstly, an untargeted MSE method was developed by ultra-high performance liquid chromatography hyphenated with quadrupole time-of-flight mass spectrometry for global metabolite characterization. Subsequently, data pretreatment was conducted by using Progenesis QI software and screening rules. The obtained metabolite features were defined as variables for statistical analyses. Principal component analysis and chemical fingerprinting spectra suggested that five official species were differentiated from each other except for Uncaria hirsuta and Uncaria sinensis. Furthermore, orthogonal partial least squares discrimination analysis was performed to discriminate confused two species, and resulted in the discovery of nine contributing markers. Ultimately, a Support Vector Machine model was developed to recognize five species and predict origins of commercial materials. The study demonstrated that the developed strategy was effective in discrimination and recognition of confused species, and promising in tracking botanical origins of commercial materials.

6.
Anal Bioanal Chem ; 411(29): 7817-7829, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31729585

RESUMO

Despite Panax quinquefolius L. serving as a crucial source for food additives, healthcare products, and herbal medicines, unawareness of the metabolome differences among three parts (root, PQR; stem leaf, PQL; flower bud, PQF) seriously restricts its quality control. Ultra-high performance liquid chromatography/quadrupole-Orbitrap mass spectrometry (UHPLC/Q-Orbitrap-MS) was fully utilized to comprehensively identify and compare the ginsenoside compositions among PQR, PQL, and PQF. Metabolite profiling and characterization were performed by coupling reversed-phase UHPLC (a CSH C18 column) and improved untargeted data-dependent MS2 acquisition in the negative mode. A novel vehicle, "Ginsenoside Sieve," was proposed by developing fixed tolerance (± 10 mDa), discrete mass defect filtering (MDF) based on the m/z features of 499 known ginsenosides, which assisted in the screening of 71 (from 3453 ions), 89 (from 6842), and 84 (from 7369) target precursor masses for PQR, PQL, and PQF, respectively. The newly established data-dependent acquisition (DDA) approach exhibited 14% improvement in characterization of targeted components (using a PQL sample), and comparable performance in identifying the unknown, compared with conventional DDA. We could characterize 347 saponins (147 from PQR, 173 from PQL, and 195 from PQF), and 157 thereof not ever-isolated from the Panax genus. These potentially new saponins have 63 unknown masses. Subsequent untargeted metabolomics analysis unveiled 20 marker saponins, among which m-Rb1, Rb1, Ro, m-Rb2, and m-Rb1 isomer are the most important diagnostic for differentiating the three parts. Conclusively, the established improved DDA represents a potent ginsenoside characterization strategy, and the results obtained in this work would benefit better quality control of P. quinquefolius. Graphical abstract.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Flores/química , Ginsenosídeos/análise , Panax/química , Raízes de Plantas/química , Caules de Planta/química , Espectrometria de Massas em Tandem/métodos , Metabolômica , Plantas Medicinais/química
7.
Molecules ; 24(20)2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31658733

RESUMO

20(S)-Ginsenoside Rg3 (GRg3) has various bioactivities including anti-cancer effects and inhibition of autophagy. However, no reports have investigated the appearance of autophagy or the connection between autophagy and apoptosis in HeLa cells treated with 20(S)-GRg3. Cell viability was measured by CCK-8 (cell counting kit-8) assays. Apoptosis and the cell cycle were analyzed by Hoechst 33342 staining and flow cytometry. Apoptotic pathways were examined by ROS (reactive oxygen species) determination and rhodamine 123 assays. Western blot analysis was used to determine changes in protein levels. Autophagy induction was monitored by acidic vesicular organelle staining and EGFP-LC3 transfection. 20(S)-GRg3 inhibited autophagy of cells in a starved state, making it impossible for cells to maintain a steady state through autophagy, and then induced apoptosis. 20(S)-GRg3 blocked the late stage of autophagy (fusion of lysosomes and degradation of autophagic lysosomes), including a decrease in acidic vesicular organelle fluorescence, increased LC3 I-II conversion, accumulation of EGFP-LC3 fluorescence, GFP-mRFP-LC3 red-green fluorescence ratio, degradation of the substrate p62, and loss of the balance between autophagy and apoptosis, which induced apoptosis. ROS increased, the mitochondrial membrane potential decreased, apoptotic inducer AIF was released from mitochondria, and nuclear transfer occurred, triggering a series of subsequent apoptotic events. Autophagy inducer rapamycin inhibited the apoptosis induced by 20(S)-GRg3, whereas autophagy inhibitor BA1 promoted apoptosis induced by 20(S)-GRg3. Therefore, 20(S)-GRg3 promoted HeLa cell apoptosis by regulating autophagy. In the autophagic state, 20(S)-GRg3 can be used as a novel autophagy inhibitor in synergy with tumor-blocking therapies such as chemotherapy, which supports its application in the medical field.

8.
Chin J Nat Med ; 17(8): 631-640, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31472901

RESUMO

Characterization of aqueous extract in traditional Chinese medicine (TCM) is challenging due to the poor retention of the analytes on conventional C18 columns. This study presents a systematic characterization method based on a rapid chromatographic separation (8 min) on a polar-modified C18 (Waters Cortecs T3) column of aqueous extract of Cordyceps sinensis. UHPLC-HRMS method was used to profile components in both untargeted and targeted manners by full MS/PIL/dd-MS2 acquisition approach. The components were identified or tentatively identified by reference standards comparison, fragmentation rules elucidation and available databases search. A total of 91 components, including 10 nucleobases, 20 nucleosides, 39 dipeptides, 18 amino acids and derivatives and 4 other components, were characterized from the aqueous extract of C. sinensis. And this was the first time to systematically report the presence of nucleosides and dipeptides in C. sinensis, especially for modified nucleosides. The chemical basis inquiry of this work would be beneficial to mechanism exploration and quality control of C. sinensis and related products. Meanwhile, this work also provided an effective solution for characterization of aqueous extract in TCM.

9.
Acta Pharm Sin B ; 9(4): 809-818, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31384540

RESUMO

Twenty-one protostane-type triterpenoids with diverse structures, including nine new compounds (1-9), were isolated from the of Alisma plantago-aquatica Linn. Structurally, alisolides A‒F (1-6), composed of an oxole group coupled to a five-membered ring, represent unusual C-17 spirost protostane-type triterpenoids. Alisolide H (8) is a novel triterpenoid with an unreported endoperoxide bridge. Alisolide I (9) represents the first example of 23,24-acetal triterpenoid. Their structures were elucidated based on spectroscopic analysis, wherein the absolute configurations of 4‒6, 8 were further confirmed by the Mo2(OAc)4-induced ECD method. Furthermore, all isolates were evaluated for their inhibitory effects on LPS-induced NO production in Caco-2 cells, and all the compounds showed remarkable inhibitory activities, with IC50 values in the range of 0.76-38.20 µmol/L.

10.
Front Pharmacol ; 10: 845, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417403

RESUMO

The sourcing of plants from multiple botanical origins is a common phenomenon in traditional Chinese medicines. Uncaria Stem with Hooks (UHs) are approved for using five botanical origins in the Chinese Pharmacopoeia (2015 Edition). All five UHs are commonly used for treating hypertension even though the plants have different chromatographic fingerprints based on our previous study. However, their hypotensive effects and metabolic phenotypes have not been fully studied. In the present study, spontaneously hypertensive rats (SHRs) were orally administered five aqueous extracts (4 g crude drug/kg) prepared from the different UHs over a 6-week period. Systolic blood pressure (SBP) was measured every week, and urine was collected after SBP measurement. Untargeted metabonomics was performed using ultra performance liquid chromatography (UPLC) coupled with an LTQ-Orbitrap mass spectrometer. Bidirectional orthogonal projection to latent structures discriminant analysis (O2PLS-DA), Student's t test, and correlation analysis were used for pattern recognition and the selection of significant metabolites. A similar and prolonged reduction in SBP was observed in each of the groups given the five different UHs, while the metabolic profiles were perturbed slightly compared with that of SHR. Further analysis has shown that only a few common, different components were observed within the five groups, which showed the similar antihypertensive effect in spite of the distinct metabolic pathways due to their different alkaloid composition. These results help in understanding the mechanisms of the phenomenon "different species, same effect" of UHs.

11.
Molecules ; 24(13)2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31269719

RESUMO

Gastrodia elata Blume (G. elata) is a valuable Traditional Chinese Medicine (TCM) with a wide range of clinical applications. G. elata polysaccharides, as one of the main active ingredients of G. elata, have interesting extraction, purification, qualitative analysis, quantitative analysis, derivatization, and pharmacological activity aspects, yet a review of G. elata polysaccharides has not yet been published. Based on this, this article summarizes the progress of G. elata polysaccharides in terms of the above aspects to provide a basis for their further research and development.


Assuntos
Gastrodia/química , Polissacarídeos/análise , Polissacarídeos/farmacologia , Antineoplásicos/farmacologia , Peso Molecular , Fármacos Neuroprotetores/farmacologia , Polissacarídeos/isolamento & purificação
12.
J Chromatogr A ; 1603: 179-189, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31255247

RESUMO

Comprehensive analysis and identification of chemical components are very important to evaluate the efficacy and safety of traditional Chinese medicine (TCM). Meanwhile, the discovery of new natural compounds is of great significance for drug exploitation and development. Although two-dimensional liquid chromatography (2D LC) systems expand the peak capacity and improve selectivity and resolution, interpreting the post-processing data is tedious and time-consuming. In this study, an off-line two-dimensional liquid chromatography/ultra-high performance supercritical fluid chromatography tandem quadrupole time-of-flight mass spectrometry (2D LC/UHPSFC-Q-TOF/MS) system was established for systematic chromatographic separation and identification of bufadienolides. Subsequently, the Global Natural Product Social Molecular Networking (GNPS) was applied for dereplication of chemical components of adjacent fractions with high efficiency and accuracy. The key parameters which affected separation and detection with respect to chromatographic conditions and mass spectrometry conditions were optimized. The extract of Venenum Bufonis was fractionated into forty fractions by first-dimensional reversed phase high-performance liquid chromatography (HPLC), which were further analyzed by the second-dimensional UHPSFC-Q-TOF/MS in positive ion mode. The data of forty fractions was imported into GNPS and processed automatically within about five hours. Furthermore, the chemical components with similar featured fragments were classified into the same cluster, which was helpful for components identification. A total of 229 bufadienolides were characterized and two subclasses of compounds (bufogenins conjugated with carboxylic acid and N-heterocyclic bufogenins) were found in Venenum Bufonis for the first time. In addition, UHPSFC exhibited powerful separation ability of isomers in Venenum Bufonis. In this analysis, two new compounds were isolated and fully characterized by NMR verifying the feasibility of this combined analytical strategy. This integrated strategy can improve the efficiency in the detection of new compounds and offer greater observation of isomers from medicinal herbs and other natural sources.


Assuntos
Bufanolídeos/isolamento & purificação , Animais , Produtos Biológicos/análise , Bufanolídeos/química , Bufonidae , Cromatografia Líquida de Alta Pressão , Cromatografia de Fase Reversa , Espectroscopia de Ressonância Magnética , Espectrometria de Massas em Tandem
13.
Phytomedicine ; 60: 152971, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31178234

RESUMO

BACKGROUND: Resibufogenin is one of the main active compounds of Venenum Bufonis and exhibits diverse pharmacological activities. It is brought into focus for its potency in heart failure and cancer therapy. PURPOSE: The purpose of this study was to establish a convenient and effective method which was used to simultaneously determine the resibufogenin and its metabolites in rat plasma for further understanding the metabolic profiles of resibufogenin in vivo and pharmacokinetic study by LC-MS/MS. METHODS: The analytes were separated on a BEH C18 column with a mobile phase of water containing 0.05% formic acid and acetonitrile under gradient elution at a flow rate of 0.4 ml/min. Resibufogenin and its eight metabolites were quantified in positive electrospray ionization and MRM mode with transitions of m/z 385.5→349.2 for resibufogenin; m/z 513.7→145.3 for IS (internal standard); m/z 401.23→365.21, m/z 417.23→285.21 and m/z 385.24→349.21 for three main metabolites (hydroxylated-resibufogenin; dihydroxylated-resibufogenin and 3-epi-resibufogenin, respectively). RESULTS: This method was successfully validated with a good linearity over the concentration ranges of 1-200 ng/ml for resibufogenin and the correlation coefficients was more than 0.990. The lower limit of quantification was 1 ng/ml and the precision and accuracy values were less than 15%. The method was applied to study the metabolic profiles of resibufogenin in rat plasma after oral administration of 20 mg/kg. The results indicated that the metabolic reactions of resibufogenin were mainly hydroxylation, dihydroxylation, dehydrogenation and isomerization. Totally eleven metabolites were identified, among which eight were successfully quantified. CONCLUSION: The results could provide further research foundation for the mechanisms study of activity and toxicity in vivo and facilitate the appropriate clinical application of resibufogenin.


Assuntos
Bufanolídeos/farmacocinética , Metaboloma , Administração Oral , Animais , Bufanolídeos/administração & dosagem , Bufanolídeos/metabolismo , Cromatografia Líquida , Estabilidade de Medicamentos , Medicamentos de Ervas Chinesas , Masculino , Ratos , Ratos Wistar , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem
14.
Molecules ; 24(9)2019 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-31035327

RESUMO

Characterization and determination of metabolites to monitor metabolic pathways play a paramount role in evaluating the efficacy and safety of medicines. However, the separation and quantification of metabolites are rather difficult due to their limited contents in vivo, especially in the case of Chinese medicine, due to its complexity. In this study, an effective and convenient method was developed to simultaneously quantify bufalin and its nine metabolites (semi-quantitation) in rat plasma after an oral administration of 10 mg/kg to rats. The prototype and metabolites that were identified were subsequently quantified using positive electrospray ionization in multiple reaction monitoring (MRM) mode with transitions of m/z 387.4→369.6 and 387.4→351.3 for bufalin, m/z 513.7→145.3 for IS, and 387.4→369.6, 419.2→365.2, and 403.2→349.2 for the main metabolites (3-epi-bufalin, dihydroxylated bufalin, and hydroxylated bufalin, respectively). The method was validated over the calibration curve range of 1.00-100 ng/mL with a limit of quantitation (LOQ) of 1 ng/mL for bufalin. No obvious matrix effect was observed, and the intra- and inter-day precisions, as well as accuracy, were all within the acceptable criteria in this method. Then, this method was successfully applied in metabolic profiling and a pharmacokinetic study of bufalin after an oral administration of 10 mg/kg to rats. The method of simultaneous determination of bufalin and its nine metabolites in rat plasma could be useful for pharmacokinetic-pharmacodynamic relationship research of bufalin, providing experimental evidence for explaining the occurrence of some adverse effects of Venenum Bufonis and its related preparations.


Assuntos
Antineoplásicos/farmacocinética , Bufanolídeos/farmacocinética , Metaboloma , Metabolômica , Animais , Antineoplásicos/química , Bufanolídeos/química , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Metabolômica/métodos , Estrutura Molecular , Controle de Qualidade , Ratos , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem
15.
Phytomedicine ; : 152918, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30979691

RESUMO

BACKGROUND: Danqi Tongmai tablet (DQTM), a combination of salvianolic acids (SA) and panax notoginsenosides (PNS), is now in phase II clinical trial developed for the treatment of cardiovascular diseases. However, the mechanisms of its protective effects through regulating endogenous metabolites remain unclear. PURPOSE: The purpose of this study was to explore the protective effects of DQTM on acute myocardial ischemia rats by comprehensive metabolomics profiling. STUDY DESIGN: The rats were divided into three groups: sham-operating, acute myocardial ischemia (AMI) and DQTM groups. The plasma and heart were collected and profiled by LC-MS based metabolomics and lipidomics. Based on the identified differential metabolites, the pathway analysis results were obtained and further validated using the network pharmacology approach. METHODS: The AMI model was induced by ligating the left anterior descending coronary artery. The metabolomics and lipidomics profiling were based on two established LC-QTOF/MS analysis methods. The raw data were processed using XCMS Online, then the differential metabolites with nonparametric t-test p value less than 0.05 were selected and identified using HMDB and METLIN. The pathway analysis was conducted using MetaboAnalyst and validated with the predicted network results obtained by BATMAN-TCM. RESULTS: The metabolomics and lipidomics profiles of plasma and heart in response to AMI and DQTM were significantly different. The AMI operation had a serious influence on metabolites in heart ischemia region, while DQTM had a greater impact on lipids in heart non-ischemia region. A total of 151 differential metabolites were identified, including mainly amino acids and fatty acids. Multiple metabolic pathways were disturbed after AMI and could be restored by DQTM, of which arachidonic acid metabolism was further validated with the predicted results of network pharmacology. CONCLUSION: The protective effects of DQTM on acute myocardial ischemia rats could be achieved through the regulation of multiple metabolic pathways.

16.
J Ethnopharmacol ; 237: 215-235, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-30905791

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The animal medicine of Venenum Bufonis (VB), a product of the secretions of Bufo gargarizans Cantor or B. melanostictus Schneider, has long been used as a traditional Chinese medicine (TCM) for the treatment of sunstroke and faint, acute filthy disease - abdominal pain or vomiting and diarrhea, etc. AIM OF THE REVIEW: This review is aimed at providing the comprehensive and up-to-date information of VB as regards its ethnopharmacological uses, constituents and their metabolism, pharmacokinetics, pharmacology and toxicology, all of which could be used as fundamental data for future research as well as development of new drugs. MATERIALS AND METHODS: The information and data about the studies of VB were collected from scientific journals, material medica, historical documents, library, and electronic databases (PubMed, Google Scholar, Science Direct, Researchgate, Web of Science and CNKI). RESULTS: To date, about 142 bufadienolides and 16 indole alkaloids have been isolated from VB in total. The extract and isolated compounds showed a wide range of in vitro and in vivo pharmacologic effects, such as cardiotonic, anti-tumor, antinociceptive, anti-inflammatory, anesthetic and antimicrobial activities. Especially, bufadienolides have been extensively studied due to its powerful anti-tumor activities against various cancer cells. Furthermore, their metabolites and metabolic pathways were concluded in detail, and the main metabolic pathways of bufadienolides were hydroxylation, 3-isomerization, 3-keto, 16-hydrolyzation, 3-O-sulfate and 3-O-glucuronide. CONCLUSIONS: Although VB possesses significant anti-tumor effect against various cancer cell lines, the development of new drugs still remains to be a challenge due to its pharmacodynamic effects in vivo, druggability and toxicology. The main problem lies in its side effects in vivo, poor bioavailability, fast metabolism, cardiotoxicity and neurovirulence. Besides, studies on its metabolism and toxicology in vitro and in vivo, as well as clinical trials should be further conducted for the new drug development and the establishment of optimal dosage of consumption of its administration.


Assuntos
Bufanolídeos , Medicina Tradicional Chinesa , Animais , Bufanolídeos/química , Bufanolídeos/farmacologia , Bufanolídeos/uso terapêutico , Humanos , Compostos Fitoquímicos/análise
17.
Chem Commun (Camb) ; 55(24): 3548-3551, 2019 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-30843551

RESUMO

We report on a naphthalimide ratiometric fluorescent probe for the real-time sensing and imaging of pathogenic bacterial glucosyltransferases, which are associated with the development of dental caries. Using a high-throughput screening method, we identified that several natural polyphenols from green tea were GTFs inhibitors that could eventually lead to suitable oral treatments to prevent the development of dental caries.


Assuntos
Corantes Fluorescentes/química , Glucosiltransferases/análise , Naftalimidas/química , Imagem Óptica/métodos , Streptococcus mutans/enzimologia , Cárie Dentária/microbiologia , Humanos , Simulação de Acoplamento Molecular
18.
J Pharm Biomed Anal ; 166: 52-65, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30609394

RESUMO

Danqi Tongmai tablet (DQTT), an innovative TCM formula under clinical trials, is composed of salvianolic acids (SA) and panax notoginsenosides (PNE) for the treatment of coronary heart disease and angina pectoris. However, the in vivo herb-herb interaction of DQTT remains unclear. In the present research, a rapid, reliable and sensitive method for quantitative analysis of multi-notoginsenoside in rat plasma based on ultra high performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-TQ/MS) was established and then applied to explore the herb-herb interaction mechanism of DQTT based on the pharmacokinetics in acute myocardial ischemia (AMI) and sham rats after oral administration of DQTT and PNE. Compared with sham rats after oral administration of PNE, the values of AUC0-t for Rf and Rb2 were significantly higher in DQTT group. Compared with AMI rats after oral PNE, AUC0-t for NR1, Rg1, Re, Rb1, Rd, Rg2, Rb2, NR2, Rh1, F1 and F2 were significantly increased after oral administration of DQTT. These results hinted that SA could improve the bioavailability of notoginsenosides in AMI rats, which provides scientific information for better understanding the herb-herb interaction mechanism and offers a reference for clinical administration of DQTT. Additionally, the presently developed methodology was simple, robust, accurate, precise, and would be useful for the pharmacokinetic studies for all kinds of notoginsenosides and other herbal saponins.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Ginsenosídeos/farmacocinética , Interações Ervas-Drogas , Panax/metabolismo , Animais , Disponibilidade Biológica , Ginsenosídeos/sangue , Masculino , Isquemia Miocárdica/sangue , Ratos , Comprimidos
19.
J Chromatogr A ; 1584: 87-96, 2019 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-30473109

RESUMO

Large-scale targeted and untargeted metabolites characterization can be achieved by feat of different liquid chromatography/mass spectrometry (LC-MS) platforms by multiple MS experiments or using data-independent acquisition followed by precursor-product ions matching based on certain algorithms. The resulting insufficiency in efficiency and availability greatly restricts the applicability of these strategies in large-scale profiling and identification of various metabolites. A strategy simultaneously enabling both the targeted and untargeted metabolites characterization is established on a Q Exactive hybrid quadrupole-Orbitrap mass spectrometer, by integrating precursor ions list-triggered data-dependent MS2 acquisition (PIL/dd-MS2) of the targeted components and using the "If idle-pick others" (IIPO) function to induce untargeted metabolites fragmentation. A compounds-specific mass defect filter (MDF) algorithm is proposed as a method to generate the PIL. As a proof of concept, this strategy coupled with offline two-dimensional liquid chromatography (2D-LC) was applied to identify the multicomponents of a traditional Chinese medicine formula Erzhi Pill (EZP). A rigid MDF vehicle was elaborated by orthogonal screening of the integer mass and integer mass-dependent dynamic mass defects considering a variation of 20 ppm. The Full MS/dd-MS2 method enabling PIL and IIPO exhibited better performance than Full MS/dd-MS2 and Targeted SIM/dd-MS2 (selected ion monitoring) in respect of the sensitivity in identifying the targeted components and the ability to characterize more untargeted ones. As a consequence, 270 components were separated from EZP, and 146 thereof were selectively characterized. In conclusion, it is a practical, multifaced strategy facilitating the in-depth metabolites profiling and characterization of complex herbal and biological samples.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/química , Espectrometria de Massas em Tandem/métodos
20.
Biomed Chromatogr ; 33(2): e4385, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30242797

RESUMO

Salvia miltiorrhiza, one of the most well-known herbal medicines, is commonly used for the treatment of coronary heart diseases in China. Besides traditional decoction slices (TDS), another relatively new product of S. miltiorrhiza, ultrafine granular powder (UGP; D90 < 45 µm), is also increasingly being used. In this paper, a UHPLC-LTQ-Orbitrap MS technique was developed for a metabolite profile study after oral administration of UGP and TDS of S. miltiorrhiza. The results showed that the number of in vivo absorbed compounds from UGP was much greater than that from TDS, and different types of products from S. miltiorrhiza will have different metabolic processes in vivo. Furthermore, a UHPLC-Q-Trap MS/MS method for simultaneously determining four tanshinones (tanshinone IIA, dihydrotanshinone I, tanshinone I and cryptotanshinone) was established and applied to assess the pharmacokinetics of the two types of products. All of the analytes displayed significant higher area under the concentration-time curve and peak concentration after oral administration of UGP than after TDS, indicating that ultrafine powder product could improve the bioavailability and absorption of cryptotanshinon,tanshinone II A,dihydrotanshinonE I and tanshinone I in vivo. The present study provides scientific information for further exploration of the pharmacology of these two types of S. miltiorrhiza and offers a reference for clinical administration of S. miltiorrhiza.


Assuntos
/sangue , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/farmacocinética , Salvia miltiorrhiza , /química , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Modelos Lineares , Masculino , Espectrometria de Massas , Pós , Ratos , Ratos Wistar , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
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