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Olea europaea L. Cv. Arbequina (OEA) (Oleaceae) is an olive variety species that has received little attention. Besides our previous work for the chemical profiling of OEA leaves using LC−HRESIMS, an additional 23 compounds are identified. An excision wound model is used to measure wound healing action. Wounds are provided with OEA (2% w/v) or MEBO® cream (marketed treatment). The wound closure rate related to vehicle-treated wounds is significantly increased by OEA. Comparing to vehicle wound tissues, significant levels of TGF-ß in OEA and MEBO® (p < 0.05) are displayed by gene expression patterns, with the most significant levels in OEA-treated wounds. Proinflammatory TNF-α and IL-1ß levels are substantially reduced in OEA-treated wounds. The capability of several lignan-related compounds to interact with MMP-1 is revealed by extensive in silico investigation of the major OEA compounds (i.e., inverse docking, molecular dynamics simulation, and ΔG calculation), and their role in the wound-healing process is also characterized. The potential of OEA as a potent MMP-1 inhibitor is shown in subsequent in vitro testing (IC50 = 88.0 ± 0.1 nM). In conclusion, OEA is introduced as an interesting therapeutic candidate that can effectively manage wound healing because of its anti-inflammatory and antioxidant properties.
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The current study accentuates the significance of performing the multiplex approach of LC-HRESIMS, biological activity, and docking studies in drug discovery, taking into consideration a review of the literature. In this regard, the investigation of antioxidant and cytotoxic activities of Trigonella stellata collected from the Egyptian desert revealed a significant antioxidant capacity using DPPH with IC50 = 656.9 µg/mL and a moderate cytotoxicity against HepG2, MCF7, and CACO2, with IC50 values of 53.3, 48.3, and 55.8 µg/mL, respectively. The evaluation of total phenolic and flavonoid contents resulted in 32.8 mg GAE/g calculated as gallic acid equivalent and 5.6 mg RE/g calculated as rutin equivalent, respectively. Chemical profiling of T. stellata extract, using LC-HRESIMS analysis, revealed the presence of 15 metabolites, among which eleven compounds were detected for the first time in this species. Interestingly, in vitro testing of the antidiabetic activity of the alcoholic extract noted an α-glucosidase enzyme inhibitory activity (IC50 = 559.4 µg/mL) better than that of the standard Acarbose (IC50 = 799.9 µg/mL), in addition to a moderate inhibition of the α-amylase enzyme (IC50 = 0.77 µg/mL) compared to Acarbose (IC50 = 0.21 µg/mL). α-Glucosidase inhibition was also virtualized by binding interactions through the molecular docking study, presenting a high binding activity of six flavonoid glycosides, as well as the diterpenoid compound graecumoside A and the alkaloid fenugreekine. Taken together, the conglomeration of LC-HRESIMS, antidiabetic activity, and molecular docking studies shed light on T. stellata as a promising antidiabetic herb.
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The current study discusses the chemical composition of the marine sponge Spongia irregularis using LC-HRESIMS. The metabolomic profiling resulted in the annotation of 17 metabolites of different chemical classes. Additionally, evaluation of the cytotoxic activities of the total extract and different fractions were carried out against three different cell lines where the n-butanol fraction exhibited the highest cytotoxic effects against HepG-2, MCF-7 and CACO-2 cell lines with IC50 values of 9.6 ± 0.02, 4.3 ± 0.10 and 5.6 ± 0.03 µg/mL, respectively. Also, the study was supported by docking study of the identified compounds for binding affinity to MSK1.
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Antineoplásicos , Poríferos , Animales , Humanos , Células CACO-2 , Océano Índico , Poríferos/química , Antineoplásicos/farmacología , Antineoplásicos/química , MetabolómicaRESUMEN
INTRODUCTION: Sponge-Coscinoderma sp. (Family: Spongiidae) is a coastal sponge that possesses a broad variety of natural-products. However, the exact chemical constituents and cytotoxic activity of the extract are still undefinable. METHODOLOGY: In the present study, the metabolomic profiling of Coscinoderma sp. dereplicated 20 compounds, utilizing liquid chromatography coupled with high-resolution mass spectrometry (LC-HRESIMS). Coscinoderma-derived crude extract, before and after encapsulation within nanosized liposomes, was in vitro screened against hepatic, breast, and colorectal carcinoma human cell lines (HepG2, MCF-7, and Caco-2, respectively). RESULTS: The identified metabolites were fit to diverse chemical classes, covering diterpenes, an indole alkaloid, sesterterpenoid, sterol, and methylherbipoline salt. Comprehensive in silico experiments predicted several compounds in the sponge-derived extract (eg, compounds 1-15) to have an anticancer potential via targeting multiple targets. The crude extract showed moderate antiproliferative activities towards studied cell lines with IC50 values range from 10.7 to 12.4 µg/mL. The formulated extract-containing liposomes (size 141±12.3nm, PDI 0.222, zeta potential 20.8 ± 2.3), significantly enhanced the in vitro anticancer activity of the entrapped extract (IC50 values ranged from 1.7 to 4.1 µg/mL). DISCUSSION: Encapsulation of both the hydrophilic and the lipophilic components of the extract within the lipid-based nanovesicles enhanced the cellular uptake and accessibility of the entrapped cargo. This study introduces liposomal nano-vesicles as a promising approach to improve the therapeutic potential of sponge-derived extracts.
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Antineoplásicos/farmacología , Mezclas Complejas/farmacología , Simulación por Computador , Liposomas/administración & dosificación , Metaboloma , Neoplasias/tratamiento farmacológico , Poríferos/química , Animales , Antineoplásicos/química , Apoptosis , Humanos , Liposomas/química , Neoplasias/metabolismo , Neoplasias/patología , Células Tumorales CultivadasRESUMEN
Bioactivity-guided fractionation of a methanolic extract of the Red Sea cucumber Holothuria spinifera and LC-HRESIMS-assisted dereplication resulted in the isolation of four compounds, three new cerebrosides, spiniferosides A (1), B (2), and C (3), and cholesterol sulfate (4). The chemical structures of the isolated compounds were established on the basis of their 1D NMR and HRMS spectral data. Metabolic profiling of the H. spinifera extract indicated the presence of diverse secondary metabolites, mostly hydroxy fatty acids, diterpenes, triterpenes, and cerebrosides. The isolated compounds were tested for their in vitro cytotoxicities against the breast adenocarcinoma MCF-7 cell line. Compounds 1, 2, 3, and 4 displayed promising cytotoxic activities against MCF-7 cells, with IC50 values of 13.83, 8.13, 8.27, and 35.56 µM, respectively, compared to that of the standard drug doxorubicin (IC50 8.64 µM). Additionally, docking studies were performed for compounds 1, 2, 3, and 4 to elucidate their binding interactions with the active site of the SET protein, an inhibitor of protein phosphatase 2A (PP2A), which could explain their cytotoxic activity. This study highlights the important role of these metabolites in the defense mechanism of the sea cucumber against fouling organisms and the potential uses of these active molecules in the design of new anticancer agents.
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Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Cerebrósidos/farmacología , Holothuria/metabolismo , Animales , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Cerebrósidos/química , Cerebrósidos/aislamiento & purificación , Proteínas de Unión al ADN/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Células HCT116 , Células HeLa , Células Hep G2 , Chaperonas de Histonas/metabolismo , Humanos , Concentración 50 Inhibidora , Células MCF-7 , Masculino , Estructura Molecular , Células PC-3 , Proteína Fosfatasa 2/metabolismo , Metabolismo Secundario , Relación Estructura-ActividadRESUMEN
Premna odorata Blanco (Lamiaceae) is an ethnomedicinal plant native to different tropical regions. Although some reports addressed their anti-inflammatory, cytotoxic, and antituberculotic effects, their hepatoprotective potential is yet to be discovered. Accordingly, this study investigated the crude extract and different fractions of the plant leaves; metabolic profiling using liquid chromatography/high-resolution electrospray ionization mass spectroscopy (LC-HRESIMS) analysis, in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties for the dereplicated metabolite via online PreADMET program, ROS scavenger activity on the Hep G2 human liver cancer cell line, and the possible hepatic cellular treatment effects in alcohol-inflamed liver female Wistar albino rats. Metabolic profiling dereplicated a total of 28 metabolites from the crude extract and its various fractions. In silico ADMET and ROS scavenger activity screening suggested plant metabolites are of potential bioactivity. In vivo hepatic treatment with crude, defatted crude, and n-hexane leave extracts suggested all extracts significantly improved liver damage, which was indicated by the reduction of elevated serum levels of bilirubin, AST, ALT, ALP, CRP, TNF-α, ICAM-1, VCAM-1, and MDA. The reduced levels of GSH and TAC were normalized during the study. Histological examinations of liver tissue showed collagen fiber distribution nearly back to its normal pattern. The anti-inflammatory and antioxidant potentials of Premna odorata extracts could be partly related to the combined effects of these phytochemicals or their synergistic interactions.
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Antiinflamatorios , Antioxidantes , Enfermedad Hepática Inducida por Sustancias y Drogas , Etanol/efectos adversos , Lamiaceae/química , Hígado , Hojas de la Planta/química , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Etanol/farmacología , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Polifenoles/química , Polifenoles/farmacología , Ratas , Ratas Wistar , Terpenos/química , Terpenos/farmacologíaRESUMEN
Bioactivity-guided isolation supported by LC-HRESIMS metabolic profiling led to the isolation of two new compounds, a ceramide, stylissamide A (1), and a cerebroside, stylissoside A (2), from the methanol extract of the Red Sea sponge Stylissa carteri. Structure elucidation was achieved using spectroscopic techniques, including 1D and 2D NMR and HRMS. The bioactive extract's metabolomic profiling showed the existence of various secondary metabolites, mainly oleanane-type saponins, phenolic diterpenes, and lupane triterpenes. The in vitro cytotoxic activity of the isolated compounds was tested against two human cancer cell lines, MCF-7 and HepG2. Both compounds, 1 and 2, displayed strong cytotoxicity against the MCF-7 cell line, with IC50 values at 21.1 ± 0.17 µM and 27.5 ± 0.18 µM, respectively. They likewise showed a promising activity against HepG2 with IC50 at 36.8 ± 0.16 µM for 1 and IC50 30.5 ± 0.23 µM for 2 compared to the standard drug cisplatin. Molecular docking experiments showed that 1 and 2 displayed high affinity to the SET protein and to inhibitor 2 of protein phosphatase 2A (I2PP2A), which could be a possible mechanism for their cytotoxic activity. This paper spreads light on the role of these metabolites in holding fouling organisms away from the outer surface of the sponge, and the potential use of these defensive molecules in the production of novel anticancer agents.
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Antineoplásicos/farmacología , Productos Biológicos/farmacología , Ceramidas/farmacología , Cerebrósidos/farmacología , Poríferos/metabolismo , Animales , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Antineoplásicos/metabolismo , Productos Biológicos/química , Productos Biológicos/aislamiento & purificación , Productos Biológicos/metabolismo , Ceramidas/química , Ceramidas/aislamiento & purificación , Ceramidas/metabolismo , Cerebrósidos/química , Cerebrósidos/aislamiento & purificación , Cerebrósidos/metabolismo , Cisplatino/farmacología , Proteínas de Unión al ADN/antagonistas & inhibidores , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/metabolismo , Ensayos de Selección de Medicamentos Antitumorales , Células Hep G2 , Chaperonas de Histonas/antagonistas & inhibidores , Chaperonas de Histonas/química , Chaperonas de Histonas/metabolismo , Humanos , Océano Índico , Concentración 50 Inhibidora , Células MCF-7 , Espectroscopía de Resonancia Magnética , Simulación del Acoplamiento Molecular , Estructura Molecular , Metabolismo SecundarioRESUMEN
The diversity of actinomycetes associated with the marine sponge Coscinoderma mathewsi collected from Hurghada (Egypt) was studied. Twenty-three actinomycetes were separated and identified based on the 16S rDNA gene sequence analysis. Out of them, three isolates were classified as novel species of the genera Micromonospora, Nocardia, and Gordonia. Genome sequencing of actinomycete strains has revealed many silent biosynthetic gene clusters and has shown their exceptional capacity for the production of secondary metabolites, not observed under classical cultivation conditions. Therefore, the effect of mycolic-acid-containing bacteria or mycolic acid on the biosynthesis of cryptic natural products was investigated. Sponge-derived actinomycete Micromonospora sp. UA17 was co-cultured using liquid fermentation with two mycolic acid-containing actinomycetes (Gordonia sp. UA19 and Nocardia sp. UA 23), or supplemented with pure mycolic acid. LC-HRESIMS data were analyzed to compare natural production across all crude extracts. Micromonospora sp. UA17 was rich with isotetracenone, indolocarbazole, and anthracycline analogs. Some co-culture extracts showed metabolites such as a chlorocardicin, neocopiamycin A, and chicamycin B that were not found in the respective monocultures, suggesting a mycolic acid effect on the induction of cryptic natural product biosynthetic pathways. The antibacterial, antifungal, and antiparasitic activities for the different cultures extracts were also tested.
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In the present study, LC-HRESIMS-assisted dereplication along with bioactivity-guided isolation led to targeting two brominated oxindole alkaloids (compounds 1 and 2) which probably play a key role in the previously reported antibacterial, antibiofilm, and cytotoxicity of Callyspongia siphonella crude extracts. Both metabolites showed potent antibacterial activity against Gram-positive bacteria, Staphylococcus aureus (minimum inhibitory concentration (MIC) = 8 and 4 µg/mL) and Bacillus subtilis (MIC = 16 and 4 µg/mL), respectively. Furthermore, they displayed moderate biofilm inhibitory activity in Pseudomonas aeruginosa (49.32% and 41.76% inhibition, respectively), and moderate in vitro antitrypanosomal activity (13.47 and 10.27 µM, respectively). In addition, they revealed a strong cytotoxic effect toward different human cancer cell lines, supposedly through induction of necrosis. This study sheds light on the possible role of these metabolites (compounds 1 and 2) in keeping fouling organisms away from the sponge outer surface, and the possible applications of these defensive molecules in the development of new anti-infective agents.
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Alcaloides/farmacología , Callyspongia/química , Oxindoles/farmacología , Animales , Antiinfecciosos/farmacología , Antiprotozoarios/farmacología , Bacterias/efectos de los fármacos , Biopelículas/efectos de los fármacos , Línea Celular Tumoral , Células HT29 , Halogenación , Humanos , Océano Índico , Pruebas de Sensibilidad Microbiana/métodosRESUMEN
BACKGROUND: In the context of a balanced diet, the antioxidant-rich food consumption is a preventive way of many degenerative diseases. Consequently, improving the nutraceutical quality of traditional foods such as bakery products is an interesting approach. Considering the present consumer's demand, cladodes from prickly pear that were traditionally used as a valuable food as well as in folk medicine for the treatment of several chronic diseases were investigated for their use in bread production to improve its functionality. METHODS: Bioactive substances were determined by liquid chromatography-high resolution electrospray ionization mass spectrometry (LC-HRESIMS) analysis. Dough rheological properties were characterized by alveographic measurements. Bread antioxidant quality was evaluated by total phenolics content, DPPH⢠radical-scavenging, metal (Fe2+) chelating and Fe3+ reducing power determinations. RESULTS: LC-HRESIMS analysis of the cladodes extract allowed the identification of 9 flavonoids, 2 phenolics, 1 alkaloid and 1 terpenoid compounds. Cladodes powder enrichment induced important modifications on the dough rheological parameters in terms of the extensibility (L) and deformation energy (W) decrease. Moreover, cladodes powder addition to bread resulted in a decrease in both crust and crumb colour parameters (L*, a* and b*). A 5% supplementation resulted in an increase of the bread yield and bread specific volume by 8.9 and 25%, respectively. Interestingly, Bread containing cladodes powder showed enhanced total phenolics content and antioxidant potential as compared to the control. CONCLUSIONS: Substitution of wheat flour by the cladodes powder at 5% level was optimal for improving the total phenolics content and the antioxidant potential of bread without having any negative effect on its sensory acceptability. Cladodes from Opuntia ficus-indica could be considered as a potential health-promoting functional ingredient in bakery products.