scholarly journals Cytotoxic Fractions from Hechtia glomerata Extracts and p-Coumaric Acid as MAPK Inhibitors

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1096
Author(s):  
Tommaso Stefani ◽  
Antonio Romo-Mancillas ◽  
Juan J. J. Carrizales-Castillo ◽  
Eder Arredondo-Espinoza ◽  
Karla Ramírez-Estrada ◽  
...  
Keyword(s):  
Cell Lines ◽  
Active Sites ◽  
High Performance ◽  
Mapk Signaling ◽  
Mass Spectrometry Analysis ◽  
Breast Adenocarcinoma ◽  
Coumaric Acid ◽  
Molecular Docking Study ◽  
Spectrometry Analysis ◽  
Mapk Inhibitors

Preliminary bioassay-guided fractionation was performed to identify cytotoxic compounds from Hechtia glomerata, a plant that is used in Mexican ethnomedicine. Organic and aqueous extracts were prepared from H. glomerata’s leaves and evaluated against two cancer cell lines. The CHCl3/MeOH (1:1) active extract was fractionated, and the resulting fractions were assayed against prostate adenocarcinoma PC3 and breast adenocarcinoma MCF7 cell lines. Active fraction 4 was further analyzed by high-performance liquid chromatography–quadrupole time-of-flight–mass spectrometry analysis to identify its active constituents. Among the compounds that were responsible for the cytotoxic effects of this fraction were flavonoids, phenolic acids, and aromatic compounds, of which p-coumaric acid (p-CA) and its derivatives were abundant. To understand the mechanisms that underlie p-CA cytotoxicity, a microarray assay was performed on PC3 cells that were treated or not with this compound. The results showed that mitogen-activated protein kinases (MAPKs) that regulate many cancer-related pathways were targeted by p-CA, which could be related to the reported effects of reactive oxygen species (ROS). A molecular docking study of p-CA showed that this phenolic acid targeted these protein active sites (MAPK8 and Serine/Threonine protein kinase 3) at the same binding site as their inhibitors. Thus, we hypothesize that p-CA produces ROS, directly affects the MAPK signaling pathway, and consequently causes apoptosis, among other effects. Additionally, p-CA could be used as a platform for the design of new MAPK inhibitors and re-sensitizing agents for resistant cancers.

scholarly journals Identification and Quantification of Coumarins by UHPLC-MS in Arabidopsis Thaliana Natural Populations

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1804
Author(s):  
Izabela Perkowska ◽  
Joanna Siwinska ◽  
Alexandre Olry ◽  
Jérémy Grosjean ◽  
Alain Hehn ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
High Performance ◽  
Biological Activities ◽  
Natural Populations ◽  
Biologically Active ◽  
Stress Factors ◽  
Mass Spectrometry Analysis ◽  
Engineering Research ◽  
Spectrometry Analysis ◽  
Model Plant Arabidopsis Thaliana

Coumarins are phytochemicals occurring in the plant kingdom, which biosynthesis is induced under various stress factors. They belong to the wide class of specialized metabolites well known for their beneficial properties. Due to their high and wide biological activities, coumarins are important not only for the survival of plants in changing environmental conditions, but are of great importance in the pharmaceutical industry and are an active source for drug development. The identification of coumarins from natural sources has been reported for different plant species including a model plant Arabidopsis thaliana. In our previous work, we demonstrated a presence of naturally occurring intraspecies variation in the concentrations of scopoletin and its glycoside, scopolin, the major coumarins accumulating in Arabidopsis roots. Here, we expanded this work by examining a larger group of 28 Arabidopsis natural populations (called accessions) and by extracting and analysing coumarins from two different types of tissues–roots and leaves. In the current work, by quantifying the coumarin content in plant extracts with ultra-high-performance liquid chromatography coupled with a mass spectrometry analysis (UHPLC-MS), we detected a significant natural variation in the content of simple coumarins like scopoletin, umbelliferone and esculetin together with their glycosides: scopolin, skimmin and esculin, respectively. Increasing our knowledge of coumarin accumulation in Arabidopsis natural populations, might be beneficial for the future discovery of physiological mechanisms of action of various alleles involved in their biosynthesis. A better understanding of biosynthetic pathways of biologically active compounds is the prerequisite step in undertaking a metabolic engineering research.

scholarly journals A Comparative Study of the Antioxidative Effects of Helichrysum italicum and Helichrysum arenarium Infusions

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 380
Author(s):  
Katja Kramberger ◽  
Zala Jenko Pražnikar ◽  
Alenka Baruca Arbeiter ◽  
Ana Petelin ◽  
Dunja Bandelj ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Performance ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Morphological Type ◽  
Mass Spectrometry Analysis ◽  
In Vitro Assays ◽  
Spectrometry Analysis ◽  
Stress Related Genes

Helichrysum arenarium (L.) Moench (abbrev. as HA) has a long tradition in European ethnomedicine and its inflorescences are approved as a herbal medicinal product. In the Mediterranean part of Europe, Helichrysum italicum (Roth) G. Don (abbrev. as HI) is more common. Since infusions from both plants are traditionally used, we aimed to compare their antioxidative potential using in vitro assays. Two morphologically distinct HI plants, HIa and HIb, were compared to a commercially available HA product. Genetic analysis using microsatellites confirmed a clear differentiation between HI and HA and suggested that HIb was a hybrid resulting from spontaneous hybridization from unknown HI subspecies. High-performance liquid chromatography–mass spectrometry analysis showed the highest amounts of hydroxycinnamic acids and total arzanol derivatives in HIa, whereas HIb was richest in monohydroxybenzoic acids, caffeic acids, and coumarins, and HA contained the highest amounts of flavonoids, especially flavanones. HIa exhibited the highest radical scavenging activity; it was more efficient in protecting different cell lines from induced oxidative stress and in inducing oxidative stress-related genes superoxide dismutase 1, catalase, and glutathione reductase 1. The antioxidative potential of HI was not only dependent on the morphological type of the plant but also on the harvest date, revealing important information for obtaining the best possible product. Considering the superior properties of HI compared to HA, the evaluation of HI as a medicinal plant could be recommended.

scholarly journals Development and method validation for determination of 54 pesticides in Okra by LC-MS/MS analysis

2020 ◽  
Vol 11 (1) ◽  
pp. 985-992
Author(s):  
Hymavati Muppalla ◽  
Kiranmayi Peddi
Keyword(s):  
European Union ◽  
Pesticide Residues ◽  
High Performance ◽  
Limit Of Detection ◽  
Extraction Procedure ◽  
Mass Spectrometry Analysis ◽  
Limit Of Quantification ◽  
Spectrometry Analysis ◽  
Tandem Mass Spectrometry Analysis

The presence of pesticide residues in primary and derived agricultural products raises serious health concerns for consumers across the globe. The aim of the present study was to assess the level of pesticide residues in Okra in India. A multi-residue method for the quantification of fifty-four pesticides in okra is described in this work. The present study employed a modified quick, easy cheap, effective rugged and safe (QuEChERS) extraction procedure followed by UHPLC-MS/MS (Ultra-High-Performance Liquid Chromatography coupled to Tandem Mass Spectrometry) analysis. Validation of the method was according to the guidelines given by European Union SANCO/12571/2013. The levels of validation were 10.0, 50.0 and 100 µg kg-1. The following parameters such as linearity, the limit of detection (LOD) (nearer to 0.005 mg kg-1) and limit of quantification (LOQ) (nearer to 0.01 mg kg-1) were set to be acceptable. The trueness of the method for 54 pesticides in all Okra commodities was between 80-110% with satisfactory repeatability and within-run reproducibility except for the pesticide residues such as Thiamethoxam and Fenamidone. The measurement of uncertainty for each of the pesticide was below 50% and was estimated to be in the range of 5.37% - 10.71%, which meets the criteria established in the SANCO/12571/2013 document (European Union, 2013). This method is concluded to be applicable for the determination of pesticide residues in Okra.

scholarly journals Identification of a Shared Microbiomic and Metabolomic Profile in Systemic Autoimmune Diseases

2019 ◽  
Vol 8 (9) ◽  
pp. 1291 ◽  
Author(s):  
Bellocchi ◽  
Fernández-Ochoa ◽  
Montanelli ◽  
Vigone ◽  
Santaniello ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
High Performance ◽  
16S Rrna Gene Sequencing ◽  
Study Groups ◽  
Mass Spectrometry Analysis ◽  
Rrna Gene ◽  
Operating Characteristics ◽  
Systemic Autoimmune Diseases ◽  
Spectrometry Analysis

Dysbiosis has been described in systemic autoimmune diseases (SADs), including systemic lupus erythematosus (SLE), Sjögren’s syndrome (SjS), and primary anti-phosholipid syndrome (PAPS), however the biological implications of these associations are often elusive. Stool and plasma samples from 114 subjects, including in SLE (n = 27), SjS (n = 23), PAPs (n = 11) and undifferentiated connective tissue (UCTD, n = 26) patients, and geographically-matched healthy controls (HCs, n = 27), were collected for microbiome (16s rRNA gene sequencing) and metabolome (high-performance liquid chromatography coupled to mass spectrometry) analysis to identify shared characteristics across diseases. Out of 130 identified microbial genera, a subset of 29 bacteria was able to differentiate study groups (area under receiver operating characteristics (AUROC) = 0.730 ± 0.025). A fair classification was obtained with a subset of 41 metabolic peaks out of 254 (AUROC = 0.748 ± 0.021). In both models, HCs were well separated from SADs, while UCTD largely overlapped with the other diseases. In all of the SADs pro-tolerogenic bacteria were reduced, while pathobiont genera were increased. Metabolic alterations included two clusters comprised of: (a) members of the acylcarnitine family, positively correlating with a Prevotella-enriched cluster and negatively correlating with a butyrate-producing bacteria-enriched cluster; and (b) phospholipids, negatively correlating with butyrate-producing bacteria. These findings demonstrate a strong interaction between intestinal microbiota and metabolic function in patients with SADs.

scholarly journals CBMT-07. BIOMARKERS OF AGGRESSIVENESS IN IDH MUTANT GLIOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi34-vi34
Author(s):  
Tomohiro Yamasaki ◽  
Adrian Lita ◽  
Tyrone Dowdy ◽  
Mark Gilbert ◽  
Mioara Larion
Keyword(s):  
Cell Lines ◽  
Imaging Spectroscopy ◽  
Mutant Gene ◽  
Raman Imaging ◽  
Malignant Progression ◽  
Mass Spectrometry Analysis ◽  
Live Cells ◽  
Lower Grade ◽  
Spectrometry Analysis ◽  
Idh Mutations

Abstract BACKGROUND Gliomas with isocitrate dehydrogenase (IDH) mutations in adults evolve from lower-grade gliomas to secondary glioblastomas (GBM), a fatal disease with fast progression. IDH mutation occurs early in tumorigenesis, and persistently contribute to the reprograming of glucose, lipid and amino acid metabolism. This offer a plethora of potential biomarkers of progression. However, because it is extremely difficult to detect the distribution and transfer of metabolites changing in every moment in a single cell, the involvement of metabolites produced by mutant IDH in malignant progression remains understudied. MATERIALS AND METHODS Raman imaging spectroscopy, which can image chemical bonds and concentration of molecules at submicron spatial resolution, enables detection of spatiotemporal changes of metabolomes in live cells. We developed the software called Biomolecular Component Analysis (BCAbox) to deconvolute the recorded raw Raman spectra, leading to detection of unique spectral features of different classes of biomolecules. RESULTS AND CONCLUSIONS We applied Raman imaging spectroscopy to GBM cell lines that were transfected with IDH1 mutant gene. Our results indicated that lipid metabolism has a unique profile in IDH1 mutant gliomas. Subsequent mass spectrometry analysis of extracted organelle revealed the exact classes of lipids altered in the IDH mutant glioma and suggested biomarkers unique to IDH1 mutant. We will report our validation studies of the biomarkers in patient-derived IDH mutant glioma cell lines and patients derived-orthotopic xenograft mouse models with different degrees of aggressiveness and in matched primary versus recurrent gliomas. The results of the present study may provide novel insights into the discovery of metabolic biomarkers for the malignant progression in IDH mutant gliomas.

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