Metabolic profiling of cytotoxic metabolites from five Tabebuia species supported by molecular correlation analysis.
Ontology highlight
ABSTRACT:
SUBMITTER: El-Hawary SS
PROVIDER: S-EPMC8052319 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Genus Tabebuia is famous for its traditional uses and valuable phytoconstituents. Our previous investigation of Tabebuia species noted the promising anticancer activity of T. guayacan Hemsl. leaves extract, however, the mechanism underlying the observed anticancer activity is still unexplored. The current research was designed to explore the phytochemical content as well as to address the phytoconstituent(s) responsible for the recorded anticancer activity. Accordingly, sixteen compounds were isolated, and their structures were elucidated using different spectroscopic techniques. The drug-likeness of the isolated compounds, as well as their binding affinity with four anticancer drug target receptors: CDK-2/6, topoisomerase-1, and VEGFR-2, were evaluated. Additionally, the most promising compounds were in vitro evaluated for inhibitory activities against CDK-2/6 and VEGFR-2 enzymes using kinase assays method. Corosolic acid (3) and luteolin-7-O-β-glucoside (16) were the most active inhibitors against CDK-2 (-13.44 kcal/mol) and topoisomerase 1 (-13.83 kcal/mol), respectively. Meanwhile, quercetin 3-O-β-xyloside (10) scored the highest binding free energies against both CDK-6 (-16.23 kcal/mol) as well as against VEGFR-2 protein targets (-10.39 kcal/mol). Molecular dynamic simulation indicated that quercetin 3-O-β-xyloside (10) exhibited the least fluctuations and deviations from the starting binding pose with RMSD (2.6 Å). Interestingly, in vitro testing results confirmed the potent activity of 10 (IC50 = 0.154 µg/mL) compared to IC50 = 0.159 µg/mL of the reference drug ribociclib. These findings suggest the three noted compounds (3, 10, and 16) for further in vivo anticancer studies.
| S-EPMC9002841 | biostudies-literature
Project description:The in-vitro anti-proliferative evaluation of Sinularia levi total extract against three cell lines revealed its potent effect against Caco-2 cell line with IC50 3.3 μg/mL, followed by MCF-7 and HepG-2 with IC50 6.4 μg/mL and 8.5 μg/mL, respectively, in comparison to doxorubicin. Metabolic profiling of S. levi total extract using liquid chromatography coupled with high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS) revealed the presence of phytoconstituents clusters consisting mainly of steroids and terpenoids (1-20), together with five metabolites 21-25, which were additionally isolated and identified through the phytochemical investigation of S. levi total extract through various chromatographic and spectroscopic techniques. The isolated metabolites included one sesquiterpene, two steroids and two diterpenes, among which compounds prostantherol (21) and 12-hydroperoxylsarcoph-10-ene (25) were reported for the first time in Sinularia genus. The cytotoxic potential evaluation of the isolated compounds revealed variable cytotoxic effects against the three tested cell lines. Compound 25 was the most potent with IC50 value of 2.13 ± 0.09, 3.54 ± 0.07 and 5.67 ± 0.08 μg/mL against HepG-2, MCF-7 and Caco-2, respectively, followed by gorgosterol (23) and sarcophine (24). Additionally, network analysis showed that cyclin-dependent kinase 1 (CDK1) was encountered in the mechanism of action of the three cancer types. Molecular docking analysis revealed that CDK1 inhibition could possibly be the reason for the cytotoxic potential.
| S-EPMC10846738 | biostudies-literature
Project description:The marine fungus Neosartorya pseudofischeri was isolated from Acanthaster planci from the South China Sea. In a preliminary bioactivity screening, the crude methanol extract of the fungal mycelia showed significant inhibitory activity against the Sf9 cell line from the fall armyworm Spodoptera frugiperda. Five novel compounds, including 5-olefin phenylpyropene A (1), 13-dehydroxylpyripyropene A (4), deacetylsesquiterpene (7), 5-formyl-6-hydroxy-8-isopropyl-2- naphthoic acid (9) and 6,8-dihydroxy-3-((1E,3E)-penta-1,3-dien-1-yl)isochroman-1-one (10), together with eleven known compounds, phenylpyropene A (2) and C (3), pyripyropene A (5), 7-deacetylpyripyropene A (6), (1S,2R,4aR,5R,8R,8aR)-1,8a-dihydroxy-2-acetoxy-3,8-dimethyl-5- (prop-1-en-2-yl)-1,2,4a, 5,6,7,8,8a-octahydronaphthalene (8), isochaetominine C (11), trichodermamide A (12), indolyl-3-acetic acid methyl ester (13), 1-acetyl-β-carboline (14), 1,2,3,4-tetrahydro-6-hydroxyl-2-methyl-l,3,4-trioxopyrazino[l,2-a]-indole (15) and fumiquinazoline F (16), were obtained. The structures of these compounds were determined mainly by MS and NMR data. The absolute configuration of 9 was assigned by the single-crystal X-ray diffraction studies. Compounds 1-11 and 15 showed significant cytotoxicity against the Sf9 cells from S. frugiperda.
| S-EPMC4728515 | biostudies-literature
Project description:Even though legumes are valuable medicinal plants with edible seeds that are extensively consumed worldwide, there is little information available on the metabolic variations between different dietary beans and their influence as potential anti-cholinesterase agents. High-resolution liquid chromatography coupled with mass spectrometry in positive and negative ionization modes combined with multivariate analysis were used to explore differences in the metabolic profiles of five commonly edible seeds, fava bean, black-eyed pea, kidney bean, red lentil, and chickpea. A total of 139 metabolites from various classes were identified including saponins, alkaloids, phenolic acids, iridoids, and terpenes. Chickpea showed the highest antioxidant and anti-cholinesterase effects, followed by kidney beans. Supervised and unsupervised chemometric analysis determined that species could be distinguished by their different discriminatory metabolites. The major metabolic pathways in legumes were also studied. Glycerophospholipid metabolism was the most significantly enriched KEGG pathway. Pearson's correlation analysis pinpointed 18 metabolites that were positively correlated with the anti-cholinesterase activity. Molecular docking of the biomarkers to the active sites of acetyl- and butyryl-cholinesterase enzymes revealed promising binding scores, validating the correlation results. The present study will add to the metabolomic analysis of legumes and their nutritional value and advocate their inclusion in anti-Alzheimer's formulations.
| S-EPMC11344142 | biostudies-literature
Project description:One of the most severe human health problems is gastric ulceration. The main aim of our study is to explore the gastroprotective effect of the Psidium guajava seeds extract (PGE). Metabolic profiling based on LC-HRMS for the extract led to the dereplication of 23 compounds (1-23). We carried out a gastric ulcer model induced by indomethacin in male albino rats in vivo and the extract of PGE was investigated at a dose of 300 mg/kg in comparison to cimetidine (100 mg/kg). Furthermore, the assessment of gastric mucosal lesions and histopathology investigation of gastric tissue was done. It has been proved that Psidium guajava seeds significantly decreased the ulcer index and protected the mucosa from lesions. The antiulcer effect of Psidium guajava seed extract, which has the power of reducing the ensuing inflammatory reactions, can counteract the inflammation induced by indomethacin by the downregulation of relative genes expression (IL-1β, IL-6, and TNF-α). Moreover, PGE significantly downregulated the increased COX-2, TGF-β, and IGF-1 relative genes expression, confirming its beneficial effect in ulcer healing. Moreover, the possible PGE antioxidant potential was determined by in vitro assays using hydrogen peroxide and superoxide radical scavenging and revealed high antioxidant potential. Additionally, on the putatively annotated metabolites, an in silico study was conducted, which emphasized the extract's antiulcer properties might be attributed to several sterols such as stigmasterol and campesterol. The present study provided evidence of Psidium guajava seeds considered as a potential natural gastroprotective agent.
| S-EPMC9311959 | biostudies-literature
Project description:Gastric ulceration is among the most serious humanpublic health problems. Olea europea L. cv. Arbequina is one of the numerous olive varieties which have scarcely been studied. The reported antioxidant and anti-inflammatory potential of the olive plant make it a potential prophylactic natural product against gastric ulcers. Consequently, the main goal of this study is to investigate the gastroprotective effect of Olea europea L. cv. Arbequina leaf extract. LC-HRMS-based metabolic profiling of the alcoholic extract of Olea europea L. cv. Arbequina led to the dereplication of 18 putative compounds (1-18). In vivo indomethacin-induced gastric ulcer in a rat model was established and the Olea europea extract was tested at a dose of 300 mg kg-1 compared to cimetidine (100 mg kg-1). The assessment of gastric mucosal lesions and histopathology of gastric tissue was done. It has been proved that Olea europea significantly decreased the ulcer index and protected the mucosa from lesions. The antioxidant potential of the extract was evaluated using three in vitro assays, H2O2 scavenging, xanthine oxidase inhibitory, and superoxide radical scavenging activities and showed promising activities. Moreover, an in silico based study was performed on the putatively dereplicated compounds, which highlighted that 3-hydroxy tyrosol (4) and oleacein (18) can target the 5-lipoxygenase enzyme (5-LOX) as a protective mechanism against the pathogenesis of ulceration. Upon experimental validation, both compounds 3-hydroxy tyrosol (HT) and oleacein (OC) (4 and 18, respectively) exhibited a significant in vitro 5-LOX inhibitory activity with IC50 values of 8.6 and 5.8 µg/mL, respectively. The present study suggested a possible implication of O. europea leaves as a potential candidate having gastroprotective, antioxidant, and 5-LOX inhibitory activity for the management of gastric ulcers.
| S-EPMC8146603 | biostudies-literature
Project description:Cellular metabolism regulates immune cell activation, differentiation and effector functions, but current metabolic approaches lack single-cell resolution and simultaneous characterization of cellular phenotype. In this study, we developed an approach to characterize the metabolic regulome of single cells together with their phenotypic identity. The method, termed single-cell metabolic regulome profiling (scMEP), quantifies proteins that regulate metabolic pathway activity using high-dimensional antibody-based technologies. We employed mass cytometry (cytometry by time of flight, CyTOF) to benchmark scMEP against bulk metabolic assays by reconstructing the metabolic remodeling of in vitro-activated naive and memory CD8+ T cells. We applied the approach to clinical samples and identified tissue-restricted, metabolically repressed cytotoxic T cells in human colorectal carcinoma. Combining our method with multiplexed ion beam imaging by time of flight (MIBI-TOF), we uncovered the spatial organization of metabolic programs in human tissues, which indicated exclusion of metabolically repressed immune cells from the tumor-immune boundary. Overall, our approach enables robust approximation of metabolic and functional states in individual cells.
| S-EPMC7878201 | biostudies-literature
Project description:Estrogen receptor (ER)-positive breast cancers overall have a good prognosis, however, some patients suffer relapses and do not respond to endocrine therapy. The purpose of this study was to determine whether there are any correlations between high-resolution magic angle spinning (HR-MAS) magnetic resonance spectroscopy (MRS) metabolic profiles of core needle biopsy (CNB) specimens and the molecular markers currently used in patients with ER-positive breast cancers. The metabolic profiling of CNB samples from 62 ER-positive cancers was performed by HR-MAS MRS. Metabolic profiles were compared according to human epidermal growth factor receptor 2 (HER2) and Ki-67 status, and luminal type, using the Mann-Whitney test. Multivariate analysis was performed with orthogonal projections to latent structure-discriminant analysis (OPLS-DA). In univariate analysis, the HER2-positive group was shown to have higher levels of glycine and glutamate, compared to the HER2-negative group (P<0.01, and P <0.01, respectively). The high Ki-67 group showed higher levels of glutamate than the low Ki-67 group without statistical significance. Luminal B cancers showed higher levels of glycine (P=0.01) than luminal A cancers. In multivariate analysis, the OPLS-DA models built with HR-MAS MR metabolic profiles showed visible discrimination between the subgroups according to HER2 and Ki-67 status, and luminal type. This study showed that the metabolic profiles of CNB samples assessed by HR-MAS MRS can be used to detect potential prognostic biomarkers as well as to understand the difference in metabolic mechanism among subtypes of ER-positive breast cancer.
| S-EPMC5609932 | biostudies-literature
Project description:ObjectiveThe aim of the study was to investigate the associations of amino acids and other polar metabolites with metabolic syndrome (MetS) in postmenopausal women in a lean Asian population.MethodsThe participants were 1,422 female residents enrolled in a cohort study from April to August 2012. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III modified for Japanese women. Associations were examined between MetS and 78 metabolites assayed in fasting plasma samples using capillary electrophoresis-mass spectrometry. Replication analysis was performed to confirm the robustness of the results in a separate population created by random allocation.ResultsAnalysis was performed for 877 naturally postmenopausal women, including 594 in the original population and 283 in the replication population. The average age, body mass index, and levels of high- and low-density lipoprotein cholesterol of the entire population were 64.6 years, 23.0?kg/m, 72.1?mg/dL, and 126.1?mg/dL, respectively. There was no significant difference in low-density lipoprotein cholesterol levels between women with and without MetS. Thirteen metabolites were significantly related to MetS: multiple plasma amino acids were elevated in women with MetS, including branched-chain amino acids, alanine, glutamate, and proline; and alpha-aminoadipate, which is generated by lysine degradation, was also significantly increased.ConclusionsOur large-scale metabolomic profiling indicates that Japanese postmenopausal women with MetS have abnormal polar metabolites, suggesting altered catabolic pathways. These results may help to understand metabolic disturbance, including in persons with normal body mass index and relatively high levels of high-density lipoprotein cholesterol, and may have clinical utility based on further studies.
| S-EPMC4927224 | biostudies-literature
Project description:PurposeTo investigate associations between imaging features of cholangiocarcinoma by visual assessment and texture analysis, which quantifies heterogeneity in tumor enhancement patterns, with molecular profiles based on hypoxia markers.MethodsThe institutional review board approved this HIPAA-compliant retrospective study of CT images of intrahepatic cholangiocarcinoma, obtained before surgery. Immunostaining for hypoxia markers (EGFR, VEGF, CD24, P53, MDM2, MRP-1, HIF-1α, CA-IX, and GLUT1) was performed on pre-treatment liver biopsies. Quantitative imaging phenotypes were determined by texture analysis with gray level co-occurrence matrixes. The correlations between quantitative imaging phenotypes, qualitative imaging features (measured by radiographic inspection alone), and expression levels of the hypoxia markers from the 25 tumors were assessed.ResultsTwenty-five patients were included with a median age of 62 years (range: 54-84). The median tumor size was 10.2 cm (range: 4-14), 10 (40%) were single tumors, and 90% were moderately differentiated. Positive immunostaining was recorded for VEGF in 67% of the cases, EGFR in 75%, and CD24 in 55%. On multiple linear regression analysis, quantitative imaging phenotypes correlated significantly with EGFR and VEGF expression levels (R2 = 0.4, p<0.05 and R2 = 0.2, p<0.05, respectively), while a trend was demonstrated with CD24 expression (R2 = 0.33, p = 0.1). Three qualitative imaging features correlated with VEGF and CD24 expression (P<0.05), however, none of the qualitative features correlated with the quantitative imaging phenotypes.ConclusionQuantitative imaging phenotypes, as defined by texture analysis, correlated with expression of specific markers of hypoxia, regardless of conventional imaging features.
| S-EPMC4514866 | biostudies-literature