scholarly journals A Comprehensive Screening and Identification of Genistin Metabolites in Rats Based on Multiple Metabolite Templates Combined with UHPLC-HRMS Analysis

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 1862 ◽  
Author(s):  
Yaoyue Liang ◽  
Wenjing Zhao ◽  
Chenxiao Wang ◽  
Zijian Wang ◽  
Zhibin Wang ◽  
...  
Keyword(s):  
Neutral Loss ◽  
Negative Ion ◽  
Ring Cleavage ◽  
Therapeutic Effects ◽  
Data Sets ◽  
Orbitrap Mass Spectrometer ◽  
Product Ions ◽  
Screening And Identification ◽  
Acquisition Method

Genistin, an isoflavone belonging to the phytoestrogen family, has been reported to possess various therapeutic effects. In the present study, the genistin metabolites in rats were investigated by UHPLC-LTQ-Orbitrap mass spectrometer in both positive and negative ion modes. Firstly, the data sets were obtained based on data-dependent acquisition method and then 10 metabolite templates were established based on the previous reports. Then diagnostic product ions (DPIs) and neutral loss fragments (NLFs) were proposed to efficiently screen and ascertain the major-to-trace genistin metabolites. Meanwhile, the calculated Clog P values were used to identify the positional isomers with different retention times. Consequently, a total of 64 metabolites, including prototype drug, were positively or putatively characterized. Among them, 40 metabolites were found according to the templates of genistin and genistein, which was the same as the previous research method. After using other metabolite templates, 24 metabolites were added. The results demonstrated that genistin mainly underwent methylation, hydrogenation, hydroxylation, glucosylation, glucuronidation, sulfonation, acetylation, ring-cleavage and their composite reactions in vivo biotransformation. In conclusion, the research not only revealed the genistein metabolites and metabolic pathways in vivo comprehensively, but also proposed a method based on multiple metabolite templates to screen and identify metabolites of other natural compounds.

scholarly journals Comprehensive Screening and Identification of Phillyrin Metabolites in Rats Based on UHPLC-Q-Exactive Mass Spectrometry Combined with Multi-Channel Data Mining

2020 ◽  
Vol 2020 ◽  
pp. 1-20
Author(s):  
Beibei Ma ◽  
Jiameng Li ◽  
Tianyu Lou ◽  
Yaoyue Liang ◽  
Chenxiao Wang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Data Mining ◽  
Neutral Loss ◽  
Negative Ion ◽  
Chromatographic Retention ◽  
Data Sets ◽  
Screening And Identification ◽  
Q Exactive ◽  
Novel Strategy

Phillyrin, a well-known bisepoxylignan, has been shown to have many critical pharmacological activities. In this study, a novel strategy for the extensive acquisition and use of data was established based on UHPLC-Q-Exactive mass spectrometry to analyze and identify the in vivo metabolites of phillyrin and to elucidate the in vivo metabolic pathways of phillyrin. Among them, the generation of data sets was mainly due to multichannel data mining methods, such as high extracted ion chromatogram (HEIC), diagnostic product ion (DPI), and neutral loss filtering (NLF). A total of 60 metabolites (including the prototype compound) were identified in positive and negative ion modes based on intuitive and useful data such as the standard’s cleavage rule, accurate molecular mass, and chromatographic retention time. The results showed that a series of biological reactions of phillyrin in vivo mainly included methylation, hydroxylation, hydrogenation, sulfonation, glucuronidation, demethylation, and dehydrogenation and their composite reactions. In summary, this study not only comprehensively explained the in vivo metabolism of phillyrin, but also proposed an effective strategy to quickly analyze and identify the metabolites of natural pharmaceutical ingredients in nature.

scholarly journals Chemical Constituent Profiling of Paecilomyces cicadae Liquid Fermentation for Astragli Radix

Molecules ◽  
2019 ◽  
Vol 24 (16) ◽  
pp. 2948 ◽  
Author(s):  
Wang ◽  
Mei ◽  
Liu ◽  
Li ◽  
Zhang ◽  
...  
Keyword(s):  
Chemical Interaction ◽  
Chemical Constituents ◽  
Neutral Loss ◽  
Chemical Constituent ◽  
Negative Ion ◽  
Chemical Components ◽  
Data Sets ◽  
Bioactive Constituents ◽  
Fermentation Liquid ◽  
Product Ions

Astragli Radix (AR) is one of the most popular traditional Chinese medicines with chemical constituents including flavonoids and saponins. As recently evidenced, some fungi or their fermentation liquid may have the potential to affect the bioactive constituents and different pharmacological effects of AR. Thus, the composition of fermented AR (FAR) produced by Paecilomyces cicadae (Miquel) Samson in liquid-state fermentation was investigated using a UHPLC-LTQ-Orbitrap mass spectrometer in both positive and negative ion modes. Firstly, the MSn data sets were obtained based on a data-dependent acquisition method and a full scan–parent ions list–dynamic exclusion (FS-PIL-DE) strategy. Then, diagnostic product ions (DPIs) and neutral loss fragments (NLFs) were proposed for better constituent detection and structural characterization. Consequently, 107 constituents in total, particularly microconstituents in FAR and AR, were characterized and compared in parallel on the same LTQ–Orbitrap instrument. Our results indicated that AR fermentation with Paecilomyces significantly influenced the production of saponins and flavonoids, especially increasing the content of astragaloside IV. In conclusion, this research was not only the first to show changes in the chemical components of unfermented AR and FAR, but it also provides a foundation for further studies on the chemical interaction between microbiota and AR.

Comprehensive and Rapid Identification of Astilbin Metabolites in Rats Based on Multiple Metabolite Templates Combined with UHPLC-Q-ExactiveMass Spectrometry

2021 ◽  
Vol 22 ◽  
Author(s):  
Shan Jiang ◽  
Haoran Li ◽  
Ailin Yang ◽  
Hongbing Zhang ◽  
Pingping Dong ◽  
...  
Keyword(s):  
Mass Spectrometer ◽  
Biological Effects ◽  
Rat Plasma ◽  
Rapid Identification ◽  
Negative Ion ◽  
Ring Cleavage ◽  
Rat Urine ◽  
Q Exactive ◽  
Negative Ion Mode

Background : Astilbin, a dihydroflavonoid compound widely found in plants, exhibits a variety of pharmacological activities and biological effects. However, little is known about the metabolism of this active compound in vivo, which is very helpful for elucidating the pharmacodynamic material basis and application of astilbin. Objective: To establish a rapid profiling and identification method for metabolites in rat urine, faeces and plasma using a UHPLC-Q-Exactive mass spectrometer in negative ion mode. Methods: In this study, a simple and rapid systematic strategy and 7 metabolite templates, which were established based on previous reports, were utilized to screen and identify astilbin metabolites. Results: As a result, a total of 72 metabolites were detected and characterized, among which 33 metabolites were found in rat urine, while 28 and 38 metabolites were characterized from rat plasma and faeces, respectively. These metabolites were presumed to be generated through ring cleavage, sulfation, dehydrogenation, methylation, hydroxylation, glucuronidation, dehydroxylation and their composite reactions. Conclusion: This study illustrated the capacity of the sensitive UHPLC-Q-Exactive mass spectrometer analytical system combined with the data-mining methods to rapidly elucidate the unknown metabolism. Moreover, the comprehensive metabolism study of astilbin provided an overall metabolic profile, which will be of great help in predicting the in vivo pharmacokinetic profiles and understanding the action mechanism of this active ingredient.

scholarly journals Variation in the Relative Isomer Abundance of Synthetic and Biologically Derived Phosphatidylethanols and Its Consequences for Reliable Quantification

2020 ◽  
Author(s):  
Marc Luginbühl ◽  
Reuben S E Young ◽  
Frederike Stoeth ◽  
Wolfgang Weinmann ◽  
Stephen J Blanksby ◽  
...  
Keyword(s):  
Reference Materials ◽  
Neutral Loss ◽  
Acyl Chain ◽  
Reversed Phase ◽  
Fatty Acyl ◽  
Negative Ion ◽  
Selected Reaction Monitoring ◽  
Fatty Acyl Chain ◽  
Blood Samples ◽  
Product Ions

Abstract Phosphatidylethanol (PEth) in human blood samples is a marker for alcohol usage. Typically, PEth is detected by reversed-phase liquid chromatography coupled with negative ion tandem mass spectrometry, investigating the fatty acyl anions released from the precursor ion upon collision-induced dissociation (CID). It has been established that in other classes of asymmetric glycerophospholipids, the unimolecular fragmentation upon CID is biased depending on the relative position (known as sn-position) of each fatty acyl chain on the glycerol backbone. As such, the use of product ions in selected-reaction-monitoring (SRM) transitions could be prone to variability if more than one regioisomer is present in either the reference materials or the sample. Here, we have investigated the regioisomeric purity of three reference materials supplied by different vendors, labeled as PEth 16:0/18:1. Using CID coupled with ozone-induced dissociation, the regioisomeric purity (% 16:0 at sn-1) was determined to be 76, 80 and 99%. The parallel investigation of the negative ion CID mass spectra of standards revealed differences in product ion ratios for both fatty acyl chain product ions and ketene neutral loss product ions. Furthermore, investigation of the product ion abundances in CID spectra of PEth within authentic blood samples appears to indicate a limited natural variation in isomer populations between samples, with the cannonical, PEth 16:0/18:1 (16:0 at sn-1) predominant in all cases. Different reference material isomer distributions led to variation in fully automated quantification of PEth in 56 authentic dried blood spot (DBS) samples when a single quantifier ion was used. Our results suggest caution in ensuring that the regioisomeric compositions of reference materials are well-matched with those of the authentic blood samples.

Clinical Trials in Thrombosis: Secondary Prevention of Myocardial Infarction

1976 ◽  
Vol 35 (01) ◽  
pp. 049-056 ◽  
Author(s):  
Christian R Klimt ◽  
P. H Doub ◽  
Nancy H Doub
Keyword(s):  
Myocardial Infarction ◽  
Secondary Prevention ◽  
Case Control ◽  
Therapeutic Effects ◽  
Case Control Studies ◽  
Definitive Answer ◽  
Inhibition Of Platelet Aggregation ◽  
Prospective Trials

SummaryNumerous in vivo and in vitro experiments, investigating the inhibition of platelet aggregation and the prevention of experimentally-induced thrombosis, suggest that anti-platelet drugs, such as aspirin or the combination of aspirin and dipyridamole or sulfinpyrazone, may be effective anti-thrombotic agents in man. Since 1971, seven randomized prospective trials and two case-control studies have been referenced in the literature or are currently being conducted, which evaluate the effects of aspirin, sulfinpyrazone, or dipyridamole in combination with aspirin in the secondary prevention of myocardial infarction. A critical review of these trials indicates a range of evidence from no difference to a favorable trend that antiplatelet drugs may serve as anti-thrombotic agents in man. To date, a definitive answer concerning the therapeutic effects of these drugs in the secondary prevention of coronary heart disease is not available.

scholarly journals An Algorithm for the Removal of Cosmic Ray Artifacts in Spectral Data Sets

2019 ◽  
Vol 73 (8) ◽  
pp. 893-901
Author(s):  
Sinead J. Barton ◽  
Bryan M. Hennelly
Keyword(s):  
Cosmic Ray ◽  
Data Sets ◽  
Biological Cells ◽  
Statistical Classification ◽  
Signal To Noise ◽  
Multivariate Statistical ◽  
Data Set ◽  
Artefact Removal ◽  
Single Capture ◽  
Acquisition Method

Cosmic ray artifacts may be present in all photo-electric readout systems. In spectroscopy, they present as random unidirectional sharp spikes that distort spectra and may have an affect on post-processing, possibly affecting the results of multivariate statistical classification. A number of methods have previously been proposed to remove cosmic ray artifacts from spectra but the goal of removing the artifacts while making no other change to the underlying spectrum is challenging. One of the most successful and commonly applied methods for the removal of comic ray artifacts involves the capture of two sequential spectra that are compared in order to identify spikes. The disadvantage of this approach is that at least two recordings are necessary, which may be problematic for dynamically changing spectra, and which can reduce the signal-to-noise (S/N) ratio when compared with a single recording of equivalent duration due to the inclusion of two instances of read noise. In this paper, a cosmic ray artefact removal algorithm is proposed that works in a similar way to the double acquisition method but requires only a single capture, so long as a data set of similar spectra is available. The method employs normalized covariance in order to identify a similar spectrum in the data set, from which a direct comparison reveals the presence of cosmic ray artifacts, which are then replaced with the corresponding values from the matching spectrum. The advantage of the proposed method over the double acquisition method is investigated in the context of the S/N ratio and is applied to various data sets of Raman spectra recorded from biological cells.

scholarly journals microRNA-186 in extracellular vesicles from bone marrow mesenchymal stem cells alleviates idiopathic pulmonary fibrosis via interaction with SOX4 and DKK1

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jing Zhou ◽  
Yang Lin ◽  
Xiuhua Kang ◽  
Zhicheng Liu ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Extracellular Vesicles ◽  
Luciferase Assay ◽  
Therapeutic Effects ◽  
Loss Of Function ◽  
Fibroblast Activation ◽  
Promising Therapeutic Approach

Abstract Background Previous reports have identified that human bone marrow mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) with their cargo microRNAs (miRNAs) are a promising therapeutic approach for the treatment of idiopathic pulmonary fibrosis (IPF). Therefore, we explored whether delivery of microRNA-186 (miR-186), a downregulated miRNA in IPF, by BMSC EVs could interfere with the progression of IPF in a murine model. Methods In a co-culture system, we assessed whether BMSC-EVs modulated the activation of fibroblasts. We established a mouse model of PF to evaluate the in vivo therapeutic effects of BMSC-EVs and determined miR-186 expression in BMSC-EVs by polymerase chain reaction. Using a loss-of-function approach, we examined how miR-186 delivered by BMSC-EVs affected fibroblasts. The putative relationship between miR-186 and SRY-related HMG box transcription factor 4 (SOX4) was tested using luciferase assay. Next, we investigated whether EV-miR-186 affected fibroblast activation and PF by targeting SOX4 and its downstream gene, Dickkopf-1 (DKK1). Results BMSC-EVs suppressed lung fibroblast activation and delayed IPF progression in mice. miR-186 was downregulated in IPF but enriched in the BMSC-EVs. miR-186 delivered by BMSC-EVs could suppress fibroblast activation. Furthermore, miR-186 reduced the expression of SOX4, a target gene of miR-186, and hence suppressed the expression of DKK1. Finally, EV-delivered miR-186 impaired fibroblast activation and alleviated PF via downregulation of SOX4 and DKK1. Conclusion In conclusion, miR-186 delivered by BMSC-EVs suppressed SOX4 and DKK1 expression, thereby blocking fibroblast activation and ameliorating IPF, thus presenting a novel therapeutic target for IPF.

scholarly journals A New Symmetrical Thiazolidinedione Derivative: In Silico Design, Synthesis, and In Vivo Evaluation on a Streptozotocin- Induced Rat Model of Diabetes

Processes ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1294
Author(s):  
Samuel Álvarez-Almazán ◽  
Gabriel Navarrete-Vázquez ◽  
Itzia Irene Padilla-Martínez ◽  
José Correa-Basurto ◽  
Diana Alemán-González-Duhart ◽  
...  
Keyword(s):  
Rat Model ◽  
In Silico ◽  
Female Rats ◽  
Therapeutic Effects ◽  
Acute Oral Toxicity ◽  
Oral Toxicity ◽  
In Vivo Evaluation ◽  
Docking Simulations ◽  
Ppar Γ

By activating PPAR-γ, thiazolidinediones normalize glucose levels in animal models of type 2 diabetes and in patients with this pathology. The aim of the present study was to analyze 219 new derivatives in silico and select the best for synthesis, to be evaluated for acute oral toxicity in female rats and for control of diabetes-related parameters in a rat model of streptozotocin-induced diabetes. The best compound was chosen based on pharmacokinetic, pharmacodynamic, and toxicological parameters obtained in silico and binding orientation observed by docking simulations on PPAR-γ. Compound 1G was synthesized by a quick and easy Knoevenagel condensation. Acute oral toxicity was found at a dose greater than 2000 mg/Kg. Compound 1G apparently produces therapeutic effects similar to those of pioglitazone, decreasing glycaemia and triglyceride levels in diabetic animals, without liver damage. Moreover, it did not cause a significant weight gain and tended to reduce polydipsia and polyphagia, while diminishing systemic inflammation related to TNF-α and IL-6. It lowered the level of endogenous antioxidant molecules such as reduced glutathione and glutathione reductase. In conclusion, 1G may be a candidate for further testing as an euglycemic agent capable of preventing the complications of diabetes.

Sign in / Sign up

Export Citation Format

Share Document