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In-Vivo Antidiabetic Activity and In-Silico Mode of Action of LC/MS-MS Identified Flavonoids in Oleaster Leaves.

ABSTRACT: BACKGROUND:Olea europea L. subsp. europaea var. sylvestris (Mill) Lehr (Oleaster) is a wild endemic olive tree indigenous to the Mediterranean region. Olea europea leaves represent a natural reservoir of bioactive molecules that can be used for therapeutic purposes. AIM OF THE STUDY:This work was conducted to study antidiabetic and antihyperglycemic activities of flavonoids from oleaster leaves using alloxan-induced diabetic mice. The mode of action of flavonoids against eight receptors that have a high impact on diabetes management and complication was also investigated using molecular docking. RESULTS:During 28 days of mice treatment with doses 25 and 50 mg/kg b.w, the studied flavonoids managed a severe diabetic state (<450 mg/dL), exhibiting a spectacular antidiabetic and antihyperglycemic activity, and improved mice health status compared to diabetic control. The in-silico mode of action of oleaster flavonoids revealed the inhibition of protein tyrosine phosphatase 1B (PTP1B), Dipeptidyl-peptidase 4 (DPP4), ?-Amylase (AAM), ?-Glucosidase inhibition, Aldose reductase (AldR), Glycogen phosphorylase (GP), and the activation of free fatty acid receptor 1 (FFAR1). CONCLUSION:The findings obtained in the present work indicate that the flavonoids from the oleaster may constitute a safe multi-target remedy to treat diabetes.

SUBMITTER: Mechchate H

PROVIDER: S-EPMC7663640 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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In-Vivo Antidiabetic Activity and In-Silico Mode of Action of LC/MS-MS Identified Flavonoids in Oleaster Leaves.

Mechchate Hamza H Es-Safi Imane I Bourhia Mohammed M Kyrylchuk Andrii A El Moussaoui Abdelfattah A Conte Raffaele R Ullah Riaz R Ezzeldin Essam E Mostafa Gamal A GA Grafov Andriy A Bekkari Hicham H Bousta Dalila D

Molecules (Basel, Switzerland) 20201101 21

<h4>Background</h4><i>Olea europea</i> L. subsp. <i>europaea</i> var. <i>sylvestris</i> (Mill) Lehr (Oleaster) is a wild endemic olive tree indigenous to the Mediterranean region. <i>Olea europea</i> leaves represent a natural reservoir of bioactive molecules that can be used for therapeutic purposes.<h4>Aim of the study</h4>This work was conducted to study antidiabetic and antihyperglycemic activities of flavonoids from oleaster leaves using alloxan-induced diabetic mice. The mode of action of ...[more]

PMID: 33139638

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Project description:BACKGROUND:Human rhinoviruses (HRVs) are responsible for more than half of all cases of the common cold and cause billions of USD annually in medical visits and school and work absenteeism. An assessment was made of the cytotoxic and antiviral activities and possible mode of action of the tannin ellagic acid from the leaves of Lagerstroemia speciosa toward HeLa cells and three rhinoviruses, HRV-2, -3, and -4. METHODS:The antiviral property and mechanism of action of ellagic acid were evaluated using a sulforhodamine B assay and real-time reverse transcription-PCR (RT-PCR) with SYBR Green dye. Results were compared with those of the currently used broad-spectrum antiviral agent, ribavirin. RESULTS:As judged by 50% inhibitory concentration values, natural ellagic acid was 1.8, 2.3, and 2.2 times more toxic toward HRV-2 (38 ?g/mL), HRV-3 (31 ?g/mL), and HRV-4 (29 ?g/mL) than ribavirin, respectively. The inhibition rate of preincubation with 50 ?g/mL ellagic acid was 17%, whereas continuous presence of ellagic acid during infection led to a significant increase in the inhibition (70%). Treatment with 50 ?g/mL ellagic acid considerably suppressed HRV-4 infection only when added just after the virus inoculation (0 h) (87% inhibition), but not before -1 h or after 1 h or later (<20% inhibition). These findings suggest that ellagic acid does not interact with the HRV-4 particles and may directly interact with the human cells in the early stage of HRV infections to protect the cells from the virus destruction. Furthermore, RT-PCR analysis revealed that 50 ?g/mL ellagic acid strongly inhibited the RNA replication of HRV-4 in HeLa cells, suggesting that ellagic acid inhibits virus replication by targeting on cellular molecules, rather than virus molecules. CONCLUSIONS:Global efforts to reduce the level of antibiotics justify further studies on L. speciosa leaf-derived materials containing ellagic acid as potential anti-HRV products or a lead molecule for the prevention or treatment of HRV infection.

Project description:The indiscriminate use of antibiotics in agriculture has raised concerns about antibiotic residues in food products, necessitating robust analytical methods for detection and quantification. In this study, our primary aim was to develop a robust and advanced liquid chromatography-tandem mass spectrometry (LC-MS/MS) methodology specifically designed for the accurate quantification of ticarcillin degradation products in tomato leaves. The choice of ticarcillin as the target analyte stems from its frequent use in agriculture and the potential formation of degradation products, which can pose a threat to food safety. The use of tomatoes as the target sample matrix in this study is justified by their significance in human diets, their widespread cultivation, and their suitability as a model for assessing antibiotic residue dynamics in diverse agricultural environments. By optimizing the MS/MS parameters, the study successfully demonstrates the practicality and reliability of the employed LC-MS/MS method in accurately assessing ticarcillin degradation product (Thiophene-2-Acetic acid and Thiophene-3-Acetic acid) levels. The chromatographic separation was achieved using a specialized column, ensuring high resolution and sensitivity in detecting analytes. Multiple reaction monitoring (MRM) data acquisition was employed to enhance the selectivity and accuracy of the analysis. The developed method exhibited excellent linearity and precision, meeting the stringent requirements for antibiotic residue analysis in complex matrices. Key outcomes of this study include the successful identification and quantification of ticarcillin and its degradation products in tomato leaves, providing crucial insights into the fate of this antibiotic in agricultural settings. The methodology's applicability was further demonstrated by analyzing real-world samples, highlighting its potential for routine monitoring and ensuring food safety compliance. In summary, our study constitutes a noteworthy advancement in the domain of antibiotic residue analysis, offering a reliable method for quantifying ticarcillin degradation products in tomato leaves. The optimized parameters and MRM-based LC-MS/MS approach enhance the precision and sensitivity of the analysis, opening up opportunities for further studies in the assessment of antibiotic residues in agricultural ecosystems.

Project description:BackgroundRuk/CIN85 is a mammalian adaptor molecule with three SH3 domains. Using its SH3 domains Ruk/CIN85 can cluster multiple proteins and protein complexes, and, consequently, facilitates organisation of elaborate protein interaction networks with diverse regulatory roles. Previous research linked Ruk/CIN85 with the regulation of vesicle-mediated transport and cancer cell invasiveness. Despite the recent findings, precise molecular functions of Ruk/CIN85 in these processes remain largely elusive and further research is hampered by a lack of complete lists of its partner proteins.ResultsIn the present study we employed a LC-MS/MS-based experimental pipeline to identify a considerable number (over 100) of proteins recruited by the SH3 domains of Ruk/CIN85 in vitro. Most of these identifications are novel Ruk/CIN85 interaction candidates. The identified proteins have diverse molecular architectures and can interact with other proteins, as well as with lipids and nucleic acids. Some of the identified proteins possess enzymatic activities. Functional profiling analyses and literature mining demonstrate that many of the proteins recruited by the SH3 domains of Ruk/CIN85 identified in this work were involved in the regulation of membranes and cytoskeletal structures necessary for vesicle-mediated transport and cancer cell invasiveness. Several groups of the proteins were also associated with few other cellular processes not previously related to Ruk/CIN85, most prominently with cell division.ConclusionObtained data support the notion that Ruk/CIN85 regulates vesicle-mediated transport and cancer cell invasiveness through the assembly of multimeric protein complexes governing coordinated remodelling of membranes and underlying cytoskeletal structures, and imply its important roles in formation of coated vesicles and biogenesis of invadopodia. In addition, this study points to potential involvement of Ruk/CIN85 in other cellular processes, chiefly in cell division.

Dataset Information

In-Vivo Antidiabetic Activity and In-Silico Mode of Action of LC/MS-MS Identified Flavonoids in Oleaster Leaves.

Publications

In-Vivo Antidiabetic Activity and In-Silico Mode of Action of LC/MS-MS Identified Flavonoids in Oleaster Leaves.

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