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Öğe Aryl benzofuran derivatives from the stem bark of Calpocalyx dinklagei attenuate inflammation(Pergamon-Elsevier Science Ltd, 2017) Kapche, Deccaux W. F. G.; Lekane, Nadege M.; Kulabas, Seda S.; Ipek, Hande; Tok, Tugba T.; Ngadjui, Bonaventure T.; Demirtas, IbrahimCalpocalyx dinklagei Harms (Fabaceae) is a tropical medicinal tree, which is indigenous to Western Africa. A phytochemical study of this local plant species from its stem bark has led to the isolation of two previously undescribed aryl benzofuran derivatives, named dinklagein A and B, together with eight known compounds. Their chemical structures were elucidated by use of extensive spectroscopic methods (IR, HREI-MS and 1D and 2D NMR). Among all isolates, dinklagein A displayed remarkably potent inhibitory activity against the production of nitric oxide (NO) in the lipopolysaccharide (LPS) induced RAW264.7 macrophages. SAR and molecular docking investigations on iNOS and previously undescribed compounds (dinklagein A and B) supported experimental data. Furthermore, dinklagein A dose dependently suppressed the LPS-stimulated iNOS expression at both mRNA and protein level. It also attenuated IL-1 beta release, mRNA expressions of IL-1 beta and COX-2 at low doses. These results suggest that dinklagein A can be developed as natural, multi-target agent against several inflammatory diseases. (C) 2017 Elsevier Ltd. All rights reserved.Öğe Biological evaluation and molecular docking. studies of nitro benzamide derivatives with respect to in vitro anti-inflammatory activity(Elsevier, 2017) Turner, Tugba B.; Onder, Ferah Comert; Ipek, Hande; Gungor, Tugba; Savranoglu, Seda; Tok, Tugba Taskin; Celik, AyhanA series of nitro substituted benzamide derivatives were synthesized and evaluated for their potential anti-inflammatory activities in vitro. Firstly, all compounds (1-6) were screened for their inhibitory capacity on LPS induced nitric oxide (NO) production in RAW264.7 macrophages. Compounds 5 and 6 demonstrated significantly high inhibition capacities in a dose-dependent manner with IC50 values of 3.7 and 53 mu M, respectively. These two compounds were also accompanied by no cytotoxicity at the studied concentrations (max 50 mu M) in macrophages. Molecular docking analysis on iNOS revealed that compounds 5 and 6 bind to the enzyme more efficiently compared to other compounds due to having optimum number of nitro groups, orientations and polarizabilities. In addition, 5 and 6 demonstrated distinct regulatory mechanisms for the expression of the iNOS enzyme at the mRNA and protein levels. Specifically, both suppressed expressions of COX-2, IL-1 beta and TNF-alpha significantly, at 10 and 20 mu M. However, only compound 6 significantly and considerably decreased LPS-induced secretion of IL-1 beta and TNF-alpha. These results suggest that compound 6 may be a multi-potent promising lead compound for further optimization in structure and as well as for in vivo validation studies. (C) 2016 Published by Elsevier B.V.Öğe Genotoxicity of pyrethrin misuse as chamomile substitute(Bayrakol Medical Publisher, 2024) Cicekliyurt, Merve M.; Akkus, Gulsum; Tufan, Begum Dermenci; Ipek, Hande; Yalcin, Sibel OymakAim: Chrysanthemum cinerariaefolium is a white-yellow, daisy-like plant known for more than one hundred fifty years of insecticide property. Although active ingredients of Chrysanthemum cinerariaefolium, pyrethrin is less toxic than organophosphate insecticides, adverse effects on immune system have been demonstrated in numerous animal studies. In our study, the genotoxic potential of accidental consumption (by mixing or unintentional causes) of Chrysanthemum cinerariaefolium instead of chamomile (Matricaria recutita) is investigated. Material and Methods: Lymphocyte isolation was performed from five male, five female donors from peripheral blood samples. Cytotoxic and genotoxic effects of pyrethrin were investigated in human peripheral lymphocyte cultures with chromosome abnormalities (CA). Micronucleus (MN), mitotic index (MI), and nucleus division index (NDI) were calculated. Cultures were treated with mixed doses of pyrethrin and chamomile in different ratios. Results: All doses compared with negative control MN, binucleate, tetranucleate, and MI were significantly increased. In the MN assay, micronucleus formation has been increased due to the gradual increase of pyrethrin/chamomile concentration. In chromosome anomaly test, results differed compared with negative and positive control, and in 24 and 48-hour applications of 1/1 mixed pyrethrin and chamomile samples were founded genotoxically. Discussion: As a result, we have observed pyrethrin has dose-related toxicity increase within the combination. We conclude that the effect of long-term accidental consumption trigger MN, binucleate, tetranucleate formation together with chromosome and chromatin type aberrations.