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    Bio-activity guided isolation of 1,5-dicaffeoyl quinic acid from Cirsium species and investigation of their therapeutic potency on melanoma through in vitro and in silico approaches
    (Springer Int Publ Ag, 2025) Sener, Sila Ozlem; Kanbolat, Seyda; Badem, Merve; Ozgen, Ufuk; Aliyazicioglu, Rezzan; Ceylan, Esma; Goren, Ahmet Ceyhan
    Melanoma exhibits a high fatality rate, and its characteristic of rapid proliferation is progressively increasing. Collagenase inhibitors are pivotal in influencing the invasion of cancer cells in melanoma. The objective of this research is to explore the therapeutic impact of specific Cirsium species on melanoma. A bioactivity-guided fractionation was carried out to identify the effective compound using collagenase inhibitory efficacy. The most potent compound underwent additional examination through in silico methods, and the presence of this compound, along with several phenolic compounds, in the most effective Cirsium species was identified using LC-MS/MS analysis. The cytotoxic effect on SK-Mel cells was assessed using the in vitro MTT technique. The bioactivity-guided fractionation study led to the identification of CTR-E1 from Cirsium trachylepis's root (CTR), and its structure was determined as 1,5-dicaffeoylquinic acid. In silico analysis revealed that 1,5-dicaffeoylquinic acid exhibited significant potency with a maximum binding affinity of - 8.19 kcal/mol, as well as hydrogen bonds and hydrophobic interactions. 1,5-dicaffeoylquinic acid, fumaric acid, pyrogallol, and epicatechin were detected and quantified in CTR by LC-MS/MS analysis. CTR was found to be effective on SK-Mel cells. Further clinical and toxicological studies, as well as additional in vitro and in vivo studies, are necessary to support the therapeutic efficacy of CTR and 1,5-dicaffeoylquinic acid.
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    Evaluation of biological activities of Barbarea integrifolia and isolation of a new glucosinolate derivated compound
    (Walter De Gruyter Gmbh, 2021) Badem, Merve; Sener, Sila Ozlem; Kanbolat, Seyda; Korkmaz, Nuriye; Yildirmis, Sermet; Ozgen, Ufuk; Aliyazicioglu, Rezzan
    The aim of the present study is to determine the potent biological activities and carry out isolation studies on Barbarea integrifolia. The antioxidant capacity of the species was evaluated by total phenolic content, FRAP, CUPRAC, and DPPH radical scavenging activity. Anticancer activity studies were performed by MTT assay in MDA-MB-231, MCF-7, Hep3B, PC-3, A549, HCT116, L-929 cell lines. It was observed that the remaining aqueous fraction has higher total phenolic content while higher activity in the CUPRAC and FRAP assays was displayed for the methanolic extract and chloroform fraction. The extracts showed anticancer activity as compared with vincristine. It was observed that chloroform fraction has the highest anticancer activity on MCF-7 cell line, while ethyl acetate fraction has the highest anticancer activity on Hep-3B and A549 cell lines. Methanolic extract has the highest anticancer activity on HCT116 and MDA-MB-23 cell lines. The isolation studies have been performed using several chromatographic methods. The chemical structures of compounds have been identified by means of H-1 NMR, C-13 NMR, 2D-NMR, and MS. Five major compounds, one steroid (beta-Sitosterol), one phenolic acid (Rosmarinic acid), one flavonol heteroside (kaempferol 7-O-alpha-L-rhamnoside-3-O-beta-D-(2-O-beta-D-glucosyl)-beta-D-glucoside), and two glucosinolates (Gluconasturtiin, Gluconasturtiin choline salt) have been isolated.
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    Investigation of therapeutic potential of three endemic Cirsium species for global health problem obesity
    (Elsevier, 2021) Sener, Sila Ozlem; Ozgen, Ufuk; Kanbolat, Seyda; Korkmaz, Nuriye; Badem, Merve; Hanci, Hatice; Dirmenci, Tuncay
    Obesity is a risk factor for metabolic disorders causes serious health problems and economic costs globally. Some Cirsium genus has been reported to possess anti-obesity effect and traditional uses for vascular diseases, anti-inflammatory and diuretic effects. This study aims to investigate the therapeutic value of endemic Cirsium species for obesity treatment. C. balikesirense Yildiz, Arabaci & Dirmenci (CB), C. nerimaniae Yildiz, Dirmenci & Arabaci (CN) and C. sommieri Petr. (CS) were selected for the study. High-fat diet (HFD) induced obese Sprague Dawley rats were employed for in vivo studies. The extract obtained aerial parts of Cirsium species were applied to rats orally for 8 weeks. To interpret the antiobesity activity, body weight of the rats were measured. Also, biochemical, histopathological and quantitative real-time PCR (RT-PCR) analysis were performed on rats. Bioactivity-guided fractionation studies were carried out guidance with in vitro lipase enzyme inhibition. The structures of the pure compounds purified using various chromatographic techniques were determined by spectroscopic methods. Oral administration of the extracts and orlistat decreased in body weights, adipocytes size, levels of serum low-density lipoprotein (LDL), triglyceride (TG), leptin levels, lipase, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and increased levels of serum high-density lipoprotein (HDL), adiponectin. According to RT-PCR analysis, the extracts reduced the levels of key transcription factors in adipogenesis and fatty acid synthase (FAS). Bioactivity-guided fractionation studies led to isolation of active compounds as syringin, cimidahurinin, astragalin, afzelin, lupeol, and psi-taraxasterol. In conclusion, CB, CN, CS and their isolated compounds were uncovered to be hopeful as a candidate for antiobesity therapeutics. (C) 2021 SAAB. Published by Elsevier B.V. All rights reserved.