22 results on '"Gurbet Celik"'
Search Results
2. Evaluation of Anti‐Alzheimer Activity of Synthetic Coumarins by Combination of in Vitro and in Silico Approaches
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Ilkay Erdogan Orhan, F. Sezer Senol Deniz, Ramin Ekhteiari Salmas, Sule Irmak, Ozden Ozgun Acar, Gurbet Celik Turgut, Alaattin Sen, Ana‐Maria Zbancioc, Simon Vlad Luca, Adrianna Skiba, Krystyna Skalicka‐Woźniak, and Gabriela Tataringa
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molecular modeling ,synthetic methods ,Molecular Medicine ,biological activity ,Bioengineering ,General Chemistry ,General Medicine ,Alzheimer's disease ,cholinesterase inhibition ,SH-SY5Y ,coumarin ,Molecular Biology ,Biochemistry - Abstract
Series of synthetic coumarin derivatives (1-16) were tested against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), two enzymes linked to the pathology of Alzheimer's disease (AD). Compound 16 was the most active AChE inhibitor with IC50 32.23±2.91 ?M, while the reference (galantamine) had IC50=1.85±0.12 ?M. Compounds 9 (IC5075.14±1.82 ?M), 13 (IC50=16.14±0.43 ?M), were determined to be stronger BChE inhibitors than the reference galantamine (IC50=93.53±2.23 ?M). The IC50 value of compound 16 for BChE inhibition (IC50=126.56±11.96 ?M) was slightly higher than galantamine. The atomic interactions between the ligands and the key amino acids inside the binding cavities were simulated to determine their ligand-binding positions and free energies. The three inhibitory coumarins (9, 13, 16) were next tested for their effects on the genes associated with AD using human neuroblastoma (SH-SY5Y) cell lines. Our data indicate that they could be considered for further evaluation as new anti-Alzheimer drug candidates. © 2022 Wiley-VHCA AG, Zurich, Switzerland.
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- 2022
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3. Evaluation of Anti‐Alzheimer Activity of Synthetic Coumarins by Combination of in Vitro and in Silico Approaches
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Erdogan Orhan, Ilkay, primary, Deniz, F. Sezer Senol, additional, Salmas, Ramin Ekhteiari, additional, Irmak, Sule, additional, Acar, Ozden Ozgun, additional, Turgut, Gurbet Celik, additional, Sen, Alaattin, additional, Zbancioc, Ana‐Maria, additional, Luca, Simon Vlad, additional, Skiba, Adrianna, additional, Skalicka‐Woźniak, Krystyna, additional, and Tataringa, Gabriela, additional
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- 2022
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4. Role of AHR, NF-kB and CYP1A1 crosstalk with the X protein of Hepatitis B virus in hepatocellular carcinoma cells
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Gurbet Celik-Turgut, Nazmiye Olmez, Tugba Koc, Ozden Ozgun-Acar, Asli Semiz, Yavuz Dodurga, Naciye Lale Satiroglu-Tufan, and Alaattin Sen
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liver cell carcinoma ,Hepatocellular carcinoma ,Hep-G2 cell line ,Nuclear factor-kappa B ,Article ,carcinogenicity ,Genetics ,controlled study ,human ,Cytochrome P4501A1 ,protein expression ,Aryl hydrocarbon receptor ,cell viability ,CYP1A1 gene ,Renilla luciferin 2 monooxygenase ,luciferase assay ,gene interaction ,human cell ,hepatitis B virus X protein ,General Medicine ,firefly luciferase ,aromatic hydrocarbon receptor ,AHR gene ,immunoglobulin enhancer binding protein ,inflammation ,real time polymerase chain reaction ,protein protein interaction ,molecular interaction ,gene expression ,NF kB gene ,coimmunoprecipitation ,cytochrome P450 1A1 ,NF kB signaling - Abstract
In this study, it was aimed to elucidate the interaction between aryl hydrocarbon receptor (AHR), nuclear factor-kappa B (NF-kB), and cytochrome P4501A1 (CYP1A1) with hepatitis B virus X protein (HBX) in a human liver cancer cell line (HepG2) transfected with HBX. First, AHR, NF-kB, and CYP1A1 genes were cloned into the appropriate region of the CheckMate mammalian two-hybrid recipient plasmids using a flexi vector system. Renilla and firefly luciferases were quantified using the dual-luciferase reporter assay system to measure the interactions. Secondly, transient transfections of CYP1A1 and NF-kB (RelA) were performed into HBX–positive and HBX–negative HepG2 cells. The mRNA expression of CYP1A1 and NF-kB genes were confirmed with RT-PCR, and cell viability was measured by WST-1. Further verification was assessed by measuring the activity and protein level of CYP1A1. Additionally, CYP1A1/HBX protein–protein interactions were performed with co-immunoprecipitation, which demonstrated no interaction. These results have clearly shown that the NF-kB and AHR genes interact with HBX without involving CYP1A1 and HBX protein–protein interactions. The present study confirms that AHR and NF-kB interaction plays a role in the HBV mechanism mediated via HBX and coordinating the carcinogenic or inflammatory responses; still, the CYP1A1 gene has no effect on this interaction. © 2022 Elsevier B.V.
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- 2022
5. Cerium Oxide Nanoparticles Biosynthesized Using Fresh Green Walnut Shell in Microwave Environment and their Anticancer Effect on Breast Cancer Cells
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Sulak, Mine, primary, Turgut, Gurbet Celik, additional, and Sen, Alaattin, additional
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- 2022
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6. Cerium Oxide Nanoparticles Biosynthesized Using Fresh Green Walnut Shell in Microwave Environment and their Anticancer Effect on Breast Cancer Cells
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Mine Sulak, Gurbet Celik Turgut, and Alaattin Sen
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protein p53 ,walnut ,cerium oxide nanoparticle ,Metal Nanoparticles ,IC50 ,MCF-7 cell line ,Biochemistry ,X-Ray Diffraction ,Spectroscopy, Fourier Transform Infrared ,genetics ,infrared spectroscopy ,Microwaves ,luciferase assay ,breast tumor ,apoptosis ,NF-kappa B ,cerium oxide nanoparticles ,General Medicine ,Cerium ,particle size ,attenuated total reflectance Fourier transform infrared spectroscopy ,immunoglobulin enhancer binding protein ,plant extract ,Molecular Medicine ,cytotoxicity ,nutshell (structure) ,ultraviolet visible spectroscopy ,Female ,scanning electron microscopy ,X ray diffraction ,Bioengineering ,Breast Neoplasms ,Juglans ,antineoplastic activity ,chemistry ,Article ,microwave cooking ,reverse transcription polymerase chain reaction ,breast cancer ,drug mechanism ,Humans ,controlled study ,human ,Molecular Biology ,P53 ,energy dispersive X ray spectroscopy ,metal nanoparticle ,Plant Extracts ,human cell ,General Chemistry ,ceric oxide ,drug structure ,microwave radiation ,NF-?B ,gene expression ,drug synthesis ,Tumor Suppressor Protein p53 - Abstract
In this study, cerium oxide nanoparticles (CONPs) were synthesized using fresh green walnut shell extract in microwave environment. The morphology and structure of the CONPs were determined using ultraviolet-visible (UV/VIS), attenuated total reflection-Fourier transform infrared (ATR-FT-IR), X-ray diffraction (XRD), energy-dispersive X-ray (EDX) spectroscopy, and scanning electron microscopy (SEM). Crystal purple staining, Annexin V-FITC detection, RT-PCR, P53, and NF-?B luciferase reporter assays were performed to evaluate the mechanism of action of CONPs in breast cancer cell lines (MCF7). The biosynthesized CONPs showed cytotoxic effects and induced apoptosis in MCF7 cells. Furthermore, CONPs induced P53 expression and suppressed NF-?B gene expression, both of which were confirmed using reporter assays. Based on the present results, it was concluded that CONPs can induce apoptosis by acting on P53 at the transcriptional level and may cause cell death by suppressing NF-?B-mediated transcription. © 2022 Wiley-VHCA AG, Zurich, Switzerland.
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- 2022
7. Inula viscosa INDUCES THE p53-DEPENDENT CELL DEATH PATHWAY IN BREAST CANCER CELLS
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Turgut, Gurbet Celik
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p53 ,Inula viscosa ,breast cancer ,p73 ,apoptosis ,Antioxidant - Abstract
Failure to activate cell death mechanisms in response to drug therapy used for breast cancer may lead to drug resistance. Therefore, knowledge of cell death mechanisms is essential for drug therapy and strategies targeting drug resistance. Although Inula viscosa (IV), widely used as a medicinal plant for traditional therapeutic purposes, can induce apoptosis in many cancers cell lines, its molecular mechanisms are not fully understood. Here, a report was presented on the apoptotic mechanism of IV in breast cancer cells. To this end, cytotoxicity of IV in breast cancer cell lines was assigned by crystal violet staining assay. RT-PCR, Western blot analysis, Annexin V-FITC apoptosis detection, p53RE luciferase assay, and p73 siRNA technique were used to evaluate the apoptotic mechanism of IV. The results indicated that N showed dose-dependent cytotoxic effects in breast cancer cell lines and induced apoptosis. As a result of IV treatment, Apaf1, Bax, Caspase 8 and 9, p53, and p73 mRNA expressions were up-regulated, but Bcl-2 gene expression level was down-regulated. In addition, it was observed that IV increased the p53 luciferase activity. Fewer cells underwent apoptosis after p73 siRNA transfection. In conclusion, IV may play a role in p53-dependent caspase activation in breast cancer cells and may also induce apoptosis in p53-mutated breast cancer cells by partially targeting p73.
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- 2022
8. Biochemical, pharmacological, and toxicological attributes of caper (
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Ozden, Ozgun-Acar, Gurbet, Celik-Turgut, Hüseyin, Guner, Serdar, Sezer, and Alaattin, Sen
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- 2021
9. In vivo examination of the effects of hydroxycinnamic acid on xenobiotic metabolizing and antioxidant enzymes
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Gurbet Celik-Turgut, Serdar Karakurt, Alaattin Sen, Sevki Arslan, Hakan Akca, Orhan Adali, Asli Semiz, and Selçuk Üniversitesi
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0301 basic medicine ,Antioxidant ,medicine.medical_treatment ,Hydroxycinnamic acids ,hydroxycinnamic acids ,Chemoprevention ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,drug-metabolizing enzymes ,antioxidant enzymes ,medicine ,chemoprevention ,Aromatase ,lcsh:QH301-705.5 ,chemistry.chemical_classification ,biology ,Glutathione peroxidase ,Glutathione ,Hydroxycinnamic acid ,030104 developmental biology ,Enzyme ,chemistry ,Biochemistry ,lcsh:Biology (General) ,Catalase ,030220 oncology & carcinogenesis ,biology.protein ,Antioxidant enzymes ,General Agricultural and Biological Sciences ,Xenobiotic ,Drug-metabolizing enzymes - Abstract
WOS: 000396702900011, In the last decade, hydroxycinnamic acids (HCA) have gained increasing attention from researchers due to their antioxidant potential. The aim of this study was to examine in detail the impact of dietary HCA on particular types of P450 and also selected phase II and antioxidant enzymes in Wistar rat. HCA (10 mu M/kg/day, i.p.) was administered for ten continuous days. Examination of the activities and mRNA and protein levels revealed that CYP2B, 2C6 and 3A enzyme activities were not altered significantly, with Western blot and qRT-PCR results corroborating this result. While treatment with HCA led to a significant reduction in CYP1A1/CYP1A2-associated enzyme activities, CYP1A1 protein, and mRNA levels were found to be unchanged. Aromatase (CYP19) activity, as well as protein and mRNA levels, were significantly reduced with HCA treatment. On the other hand, the NAD(P) H: quinone oxidoreductase 1 (NQO1), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferases (GSTs) activities were increased significantly. Also, HCA treatment significantly increased the GST-mu and GST-theta mRNA levels., Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [109R012], This study was supported by a grant from The Scientific and Technological Research Council of Turkey (109R012).
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- 2017
10. Contribution of ellagic acid on the antioxidant potential of medicinal plantEpilobium hirsutum
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Alaattin Sen, Ayse Mine Gencler-Ozkan, Gurbet Celik, Orhan Adali, Asli Semiz, and Serdar Karakurt
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Male ,0301 basic medicine ,Cancer Research ,antioxidant ,Antioxidant ,medicine.medical_treatment ,complementary DNA ,antioxidant activity ,Medicine (miscellaneous) ,Wistar rat ,Antioxidants ,Western blotting ,chemistry.chemical_compound ,0302 clinical medicine ,aspartate aminotransferase ,medicinal plant ,glutathione transferase ,NAD(P)H Dehydrogenase (Quinone) ,rat ,animal ,Epilobium ,glutathione peroxidase ,chemistry.chemical_classification ,Nutrition and Dietetics ,NQO1 protein, rat ,biology ,messenger RNA ,Glutathione peroxidase ,enzyme activity ,Oncology ,Biochemistry ,030220 oncology & carcinogenesis ,Ellagic acid ,alanine aminotransferase ,Epilobium hirsutum ,enzymology ,animal experiment ,reduced nicotinamide adenine dinucleotide (phosphate) dehydrogenase (quinone) ,liver ,Article ,reverse transcription polymerase chain reaction ,Superoxide dismutase ,03 medical and health sciences ,Ellagic Acid ,Lactate dehydrogenase ,tandem mass spectrometry ,reduced nicotinamide adenine dinucleotide phosphate ,medicine ,liquid chromatography ,Animals ,Rats, Wistar ,protein expression ,nonhuman ,Plants, Medicinal ,Superoxide Dismutase ,lactate dehydrogenase ,Glutathione ,Molecular biology ,Enzyme assay ,Rats ,030104 developmental biology ,chemistry ,drug effects ,biology.protein ,aspartate aminotransferase blood level ,metabolism ,alanine aminotransferase blood level - Abstract
In the present study, the possible role of ellagic acid (EA) on antioxidant potential of Epilobium hirsutum (EH) in rat liver was investigated. Wistar rats were intraperitoneally treated with 37.5 mg/kg of EH and 10 mg/kg of EA for 9 days. Effects of EH and EA on antioxidant [glutathione peroxidase (GPx) and superoxide dismutases (SOD)] and Phase II [NADPH quinone oxidoreductase 1 (NQO1) and glutathione S-transferases (GSTs)] enzyme activities, as well as protein and mRNA expressions of those, were investigated. Polyphenolic content of EH was determined by LC-MS/MS analysis. EH and EA injection to rats resulted in a significant increase of NQO1 (3.6-fold and 4.7-fold), GPx (1.45-fold), and SOD (1.34-fold and 1.27-fold) enzyme activities, whereas total GST (46% and 57%) and its isoforms,and GST mu (57% and 72%), and GST theta (60% and 68%) activities were significantly decreased. Western-blot and qRT-PCR analysis showed that NQO1 and GPx protein and mRNA expressions were increased significantly (P < 0.0001), whereas GST mu and GST theta were significantly decreased (P < 0.0001). © 2016 Taylor & Francis Group, LLC.
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- 2015
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11. A Comparative Study for the Evaluation of Two Doses of Ellagic Acid on Hepatic Drug Metabolizing and Antioxidant Enzymes in the Rat
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Asli Semiz, Gurbet Celik, Serdar Karakurt, Alaattin Sen, Sevki Arslan, and Orhan Adali
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Male ,antioxidant ,Antioxidant ,medicine.medical_treatment ,tissue distribution ,lcsh:Medicine ,Wistar rat ,Pharmacology ,cytochrome P450 1A ,Antioxidants ,Western blotting ,chemistry.chemical_compound ,0302 clinical medicine ,aspartate aminotransferase ,dose response ,glutathione transferase ,rat ,animal ,Tissue Distribution ,glutathione peroxidase ,oxidoreductase ,comparative study ,chemistry.chemical_classification ,cytochrome P450 2C6 ,0303 health sciences ,biology ,messenger RNA ,Glutathione peroxidase ,catalase ,drug effect ,article ,General Medicine ,CYP2E1 ,liver microsome ,unclassified drug ,enzyme activity ,3. Good health ,xenobiotic agent ,Liver ,Catalase ,030220 oncology & carcinogenesis ,blood sampling ,Oxidoreductases ,Research Article ,Ellagic acid ,aromatase ,Article Subject ,Metabolic Clearance Rate ,alanine aminotransferase ,animal experiment ,reduced nicotinamide adenine dinucleotide (phosphate) dehydrogenase (quinone) ,General Biochemistry, Genetics and Molecular Biology ,animal tissue ,in vivo study ,reverse transcription polymerase chain reaction ,03 medical and health sciences ,Ellagic Acid ,medicine ,Animals ,controlled study ,drug screening ,Rats, Wistar ,030304 developmental biology ,nonhuman ,Dose-Response Relationship, Drug ,General Immunology and Microbiology ,lcsh:R ,Glutathione ,cytochrome P450 2B ,Enzyme assay ,cytochrome P450 2C ,Rats ,Enzyme ,chemistry ,drug effects ,biology.protein ,cytochrome P450 2E1 ,aspartate aminotransferase blood level ,metabolism ,alanine aminotransferase blood level - Abstract
The present study was designed to evaluate different doses of ellagic acid (EA)in vivoin rats for its potential to modulate hepatic phases I, II, and antioxidant enzymes. EA (10 or 30 mg/kg/day, intragastrically) was administered for 14 consecutive days, and activity, protein, and mRNA levels were determined. Although the cytochrome P450 (CYP) 2B and CYP2E enzyme activities were decreased significantly, the activities of all other enzymes were unchanged with the 10 mg/kg/day EA. In addition, western-blot and qRT-PCR results clearly corroborated the above enzyme expressions. On the other hand, while the NAD(P)H:quinone oxidoreductase 1 (NQO1), catalase (CAT), glutathione peroxidase (GPX), and glutathione S-transferase (GST) activities were increased significantly, CYP1A, 2B, 2C, 2E, and 19 enzyme activities were reduced significantly with 30 mg/kg/day EA. In addition, CYP2B, 2C6, 2E1, and 19 protein and mRNA levels were substantially decreased by the 30 mg/kg/day dose of EA, but the CYP1A protein, and mRNA levels were not changed. CYP3A enzyme activity, protein and mRNA levels were not altered by neither 10 nor 30 mg/kg/day ellagic acid. These results indicate that EA exerts a dose-dependent impact on the metabolism of chemical carcinogens and drugs by affecting the enzymes involved in xenobiotics activation/detoxification and antioxidant pathways.
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- 2013
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12. CAPER (CAPPARIS OVATA) WATER EXTRACT AS AN EFFICIENT PREPARATION FOR TREATMENT OF MULTIPLE SCLEROSIS
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SEN, Alaattin, Ozgun, Ozden, Turgut, Gurbet Celik, Arslan, Sevki, Ozbal, Seda, and Ergur, Bekir
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This study was performed to elucidate the molecular mechanisms of Capparis ovata extract on experimental animal model of multiple sclerosis. Capparis ovata water extract was prepared as described (Turkish Patent Institute, PT 2012/04 093). Animal MS model, experimental allergic encephalomyelitis (EAE) was induced in 6-8 weeks old C57BL/6 mice. MSCov was given to EAE-induced mice intragastrically for 21 days, at 500 mg/kg. At the end of the treatment, RNA was isolated, and cDNA was synthesis was performed by RT-PCR in brain tissues of control, EAE and EAE-MSCOV-treated animals. Differential expression of MS marker genes such as cytokines, chemokines, inflammatory and immune response genes, as well as genes involved in cell adhesion, cellular stress and apoptosis whose expressions correlated across multiple analyses. The onset of EAE happened on day 12.0±1.5 with a maximal clinical score of 3.5±0.2. Caper extract remarkably suppressed development EAE and disease activity highly inhibited This suppression of EAE was associated with significantly reduced expression of genes that are important in inflammatory signaling while expression of genes involved in myelination was increased. These results propose mechanisms by which caper treatment deferred and smothered the development of EAE and improved the ailment in mice with persistent clinical signs., Journal of International Society of Antioxidants in Nutrition & Health, Vol 3, No 1 (2016): Journal of ISANH Volume 3: Special Issue for Antioxidants Middle East
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- 2016
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13. Essential oil composition, antioxidant activity and phenolic content of endemic Teucrium alyssifolium Staph. (Lamiaceae)
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Gurbet Celik, Asli Semiz, Gürkan Semiz, and Erhan Gönen
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Antioxidant ,antioxidant ,DPPH ,medicine.medical_treatment ,Flavonoid ,antioxidant activity ,Plant Science ,IC50 ,01 natural sciences ,Biochemistry ,Antioxidants ,Analytical Chemistry ,law.invention ,Teucrium ,chemistry.chemical_compound ,law ,Food science ,chemistry.chemical_classification ,caryophyllene ,biology ,food and beverages ,unclassified drug ,flower ,plant extract ,Teucrium alyssifolium ,Bisabolene ,GC-MS ,germander ,plant stem ,total phenolic ,phenol derivative ,bisabolene ,chemistry ,essential oil ,Article ,Phenols ,Botany ,medicine ,Oils, Volatile ,chemical composition ,flavonoid ,Teucrium alyssifolium extract ,Essential oil ,plant leaf ,Flavonoids ,total flavonoid ,nonhuman ,010405 organic chemistry ,Plant Extracts ,Organic Chemistry ,biology.organism_classification ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Polyphenol ,curcumene ,Lamiaceae - Abstract
The present study was designed to examine the chemical composition of the essential oil, in vitro antioxidant activity and total phenolic and flavonoid content of extracts from plant parts (leaf, flower and stem) of Teucrium alyssifolium. The principle components of the essential oil were trans-ß-caryophyllene (16.87%), ar-curcumene (11.43%) and bisabolene (11.06%), representing 39.36% of the oil. The total phenolic contents ranged between 13.99 and 41.54 mg of GAE/g of extract. The concentrations of flavonoids varied from 16.82 to 49.52 mg of Ru/g of extract. Antioxidant activity was determined in vitro using DPPH reagent and expressed as concentration of each extract required to inhibit radical by 50% (IC50) values that ranged from 13.52 to 132.55 µg/ml. Our results have indicated that water extract of T. alyssifolium (part leaf) with a total content of polyphenols (41.54 mg of GAE/g) and an IC50of 13.52 µg/ml is more antioxidant. © 2016 Informa UK Limited, trading as Taylor & Francis Group.
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- 2016
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14. Inhibitory Action Of Epilobium Hirsutum Extract And Its Constituent Ellagic Acid On Drug-Metabolizing Enzymes
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Orhan Adali, Alaattin Sen, Serdar Karakurt, Ayse Mine Gencler-Ozkan, Asli Semiz, Sevki Arslan, and Gurbet Celik
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Male ,0301 basic medicine ,Ellagic acid ,CYP2C6 ,CYP3A ,CYP3A1 ,benzphetamine N-demethylase ,Epilobium hirsutum extract ,Wistar rat ,Pharmacology ,benzphetamine n demethylase ,chemistry.chemical_compound ,0302 clinical medicine ,medicinal plant ,Cytochrome P-450 Enzyme System ,rat ,animal ,Pharmacology (medical) ,Epilobium ,Gallic acid ,cytochrome P450 2B1 ,enzyme inhibition ,cytochrome P450 2C6 ,biology ,erythromycin n demethylase ,unclassified drug ,enzyme activity ,030220 oncology & carcinogenesis ,Inactivation, Metabolic ,plant extract ,CYP2D2 ,Inhibition, drug-herb interaction ,gallic acid ,Drug-metabolizing enzymes ,drug inactivation ,cytochrome P450 3A1 ,medicine.drug ,drug isolation ,cytochrome P450 ,Metabolic Clearance Rate ,Epilobium hirsutum ,animal experiment ,Article ,animal tissue ,drug clearance ,in vivo study ,03 medical and health sciences ,Ellagic Acid ,In vivo ,n demethylase ,medicine ,Animals ,controlled study ,cytochrome P450 2D2 ,Rats, Wistar ,protein expression ,nonhuman ,Plants, Medicinal ,Plant Extracts ,CYP2B1 ,Cytochrome P450 ,Oxidoreductases, N-Demethylating ,Metabolism ,cytochrome P450 2D ,drug metabolism ,cytochrome P450 2C ,Rats ,030104 developmental biology ,chemistry ,drug effects ,gene expression ,adverse effects ,biology.protein ,Benzphetamine ,metabolism ,Drug metabolism - Abstract
Epilobium hirsutum (EH) is a medicinal plant for treating various diseases. Despite its wide usage, there is no available information about its potential influences on drug metabolism. The present study was undertaken to determine the in vivo effects of EH on hepatic CYP2B, CYP2C, CYP2D, and CYP3A enzymes that are primarily involved in drug metabolism. Male Wistar rats were injected intraperitoneally with EH water extract (EHWE) and ellagic acid (EA) at a daily dose of 37.5 and 20 mg/kg, respectively, for 9 days and hepatic drug-metabolizing enzymes were assessed at activity, protein and mRNA levels. Erythromycin N-demethylase activity was inhibited by 53 and 21 % in EHWE- and EA-treated rats, respectively. Benzphetamine N-demethylase and 7-benzyloxyresorufin-O-debenzylase activities were decreased by 53 and 43 %, and 57 and 57 % in EHWE-and EA-treated rats, respectively. Moreover, protein levels of CYP2B1, CYP2C6, CYP2D2, and CYP3A1 also decreased by 55, 15, 33, and 82 % as a result of EHWE treatment of rats, respectively. Similarly, CYP2B1, CYP2C6, CYP2D2, and CYP3A1 protein levels decreased by 62, 63, 49, and 37 % with EA treatment, respectively. qRT-PCR analyses also showed that mRNA levels of these enzymes were significantly inhibited with bothEHWE and EA treatments. In conclusion, inhibition of drug clearances leading to drug toxicity because of the lowered activity and expression of drug-metabolizing enzymes might be observed in the people who used EH as complementary herbal remedy that might be contributed by its EA content. © 2014 Springer International Publishing Switzerland.
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- 2016
15. Capparis ovata treatment suppresses inflammatory cytokine expression and ameliorates experimental allergic encephalomyelitis model of multiple sclerosis in C57BL/6 mice
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Ufuk Kolak, Seda Ozbal, Alaattin Sen, Isil Gazioglu, Ozden Ozgun-Acar, Sevki Arslan, Bekir Ugur Ergur, Gurbet Celik-Turgut, Gulacti Topcu, and GAZİOĞLU, IŞIL
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gamma interferon inducible protein 10 ,medicine.medical_treatment ,Encephalomyelitis ,cell infiltration ,experimental autoimmune encephalomyelitis ,myelin oligodendrocyte glycoprotein ,Transcriptome ,Mice ,0302 clinical medicine ,cytokine ,nervous system inflammation ,genetics ,tumor necrosis factor alpha ,C57BL mouse ,myelination ,Brain ,gene expression regulation ,Immunohistochemistry ,Neurology ,priority journal ,real time polymerase chain reaction ,chemically induced ,Cytokines ,antiinflammatory agent ,down regulation ,signal transduction ,Capparis ovata ,mouse model ,Immunology ,LC–MS–MS ,chemistry ,Article ,animal tissue ,03 medical and health sciences ,RANTES ,tandem mass spectrometry ,liquid chromatography ,C57BL 6 mouse ,Remyelination ,mouse ,animal model ,antiinflammatory activity ,fruit ,medicine.disease ,Peptide Fragments ,Mice, Inbred C57BL ,antigen presentation ,030104 developmental biology ,peptide fragment ,Neurology (clinical) ,myelin oligodendrocyte glycoprotein (35-55) ,transcriptome ,disease activity ,030217 neurology & neurosurgery ,Capparis ovata extract ,0301 basic medicine ,Anti-Inflammatory Agents ,multiple sclerosis ,tissue section ,immune response ,humoral immunity ,Immunology and Allergy ,animal ,innate immunity ,Experimental autoimmune encephalomyelitis ,Anti-neuroinflammatory ,gene control ,remyelinization ,Cytokine expression ,unclassified drug ,flower ,Cytokine ,medicine.anatomical_structure ,immunoglobulin enhancer binding protein ,female ,plant extract ,Myelin Proteins ,analysis of variance ,Encephalomyelitis, Autoimmune, Experimental ,animal experiment ,interleukin 6 ,immunocompetent cell ,Biology ,immunization ,Immune system ,medicine ,gene expression profiling ,Animals ,controlled study ,Transcriptome profiling ,Innate immune system ,nonhuman ,Plant Extracts ,Multiple sclerosis ,Experimental allergic encephalomyelitis ,disease model ,Ozgun-Acar O., Celik-Turgut G., Gazioglu I., Kolak U., Ozbal S., Ergur B. U. , Arslan S., Sen A., Topcu G., -Capparis ovata treatment suppresses inflammatory cytokine expression and ameliorates experimental allergic encephalomyelitis model of multiple sclerosis in C57BL/6 mice-, JOURNAL OF NEUROIMMUNOLOGY, cilt.298, ss.106-116, 2016 ,myelin protein ,phytotherapy ,bud ,Capparis ,Disease Models, Animal ,drug effects ,gene expression ,CXCL9 chemokine ,Myelin-Oligodendrocyte Glycoprotein ,metabolism - Abstract
Since ancient times, Capparis species have been widely used in traditional medicine to treat various diseases. Our recent investigations have suggested Capparis ovata-s potential anti-neuroinflammatory application for the treatment of multiple sclerosis (MS). The present study was designed to precisely determine the underlying mechanism of its anti-neuroinflammatory effect in a mouse model of MS. C. ovata water extract (COWE) was prepared using the plant-s fruit, buds, and flower parts (Turkish Patent Institute, PT 2012/04,093). We immunized female C57BL/6 J mice with MOG(35_55)/CFA. COWE was administered at a daily dose of 500 mg/Kg by oral gavage either from the day of immunization (T1) or at disease onset (12) for 21 days. Gene expression analysis was performed using a Mouse Multiple Sclerosis RT2 Profiler PCR Array, and further determinations and validations of the identified genes were performed using qPCR. Whole-genome transcriptome profiling was analyzed using Agilent SurePrint G3 Mouse GE 8X60K microarrays. Immunohistochemical staining was applied to brain sections of the control and treated mice to examine the degree of degeneration. COWE was further fractionated and analyzed phytochemically using the Zivak Tandem Gold Triple Quadrupole LC/MS-MS system. COWE remarkably suppressed the development of EAE in T1, and the disease activity was completely inhibited. In the T2 group, the maximal score was significantly reduced compared with that of the parallel EAE group. The COWE suppression of EAE was associated with a significantly decreased expression of genes that are important in inflammatory signaling, such as TNF alpha, IL6, NF-kappa B, CCL5, CXCL9, and CXCK10. On the other hand, the expression of genes involved in myelination/remyelination was significantly increased. Immunohistochemical analysis further supported these effects, showing that the number of infiltrating immune cells was decreased in the brains of COWE-treated animals. In addition, differential expression profiling of the transcriptome revealed that COWE treatment caused the down regulation of a group of genes involved in the immune response, inflammatory response, antigen processing and presentation, B-cell-mediated immunity and innate immune response. Collectively, these results suggest anti-neuroinflammatory mechanisms by which COWE treatment delayed and suppressed the development of EAE and ameliorated the disease in mice with persistent clinical signs. (C) 2016 Elsevier B.V. All rights reserved. Türkiye Bilimsel Ve Teknolojik Araştırma Kurumu ( Tübitak )
- Published
- 2016
16. The isolation of tetrangomycin from terrestrial Streptomyces sp. CAH29: evaluation of antioxidant, anticancer, and anti-MRSA activity
- Author
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Thomas P. Umile, Alaattin Sen, Gurbet Celik, Necmettin Pirinccioglu, Robert W. Davis, Kevin P. C. Minbiole, Süleyman Özakin, Murat Kizil, and Ebru Ince
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0301 basic medicine ,prostate adenocarcinoma ,antioxidant ,interleukin 1beta ,protein p53 ,cyclin D2 ,cyclin D1 ,antioxidant activity ,arginine ,IC50 ,Antimicrobial activity ,stress activated protein kinase ,medicine.disease_cause ,01 natural sciences ,synthetase ,caspase 8 ,antibacterial activity ,Tetrangomycin ,valine ,A549 cell line ,epithelium basal cell ,Candida albicans ,fermentation medium ,rhizosphere bacterium ,General Pharmacology, Toxicology and Pharmaceutics ,prostate cancer cell line ,antineoplastic agent ,biology ,Chemistry ,messenger RNA ,mitogen activated protein kinase ,Interleukin ,methicillin resistant Staphylococcus aureus ,lung alveolus epithelium ,Streptomyces ,unclassified drug ,antiinfective agent ,Interleukin 10 ,Staphylococcus aureus ,glutamine ,cytotoxicity ,enzyme binding ,leucine ,Raf protein ,Immunosuppressive activity ,protein Bax ,protein bcl 2 ,drug isolation ,RNA 16S ,Streptococcus pyogenes ,tumor necrosis factor ,Anti-MRSA ,interleukin 6 ,biological activity ,RNA sequence ,antineoplastic activity ,interleukin 2 ,Article ,Microbiology ,03 medical and health sciences ,LNCaP ,medicine ,unindexed drug ,controlled study ,human ,Interleukin 6 ,protein expression ,terrestrial species ,A549 cell ,nonhuman ,Cytotoxic activity ,010405 organic chemistry ,bacterial enzyme ,human cell ,Organic Chemistry ,antifungal activity ,Streptomyces stramineus ,Angucylines ,phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase ,molecular docking ,sequence homology ,biology.organism_classification ,lung adenocarcinoma ,LNCaP cell line ,0104 chemical sciences ,drug structure ,nuclear magnetic resonance ,030104 developmental biology ,concentration response ,bacterial extract ,biology.protein ,Streptomyces sp cah29 ,interleukin 10 ,tyrosine - Abstract
A rhizosphere isolate Streptomyces sp. CAH29 was found to possess potent antibacterial and antifungal activity against a variety of test organisms. Based on 16S ribosomal ribonucleic acid sequence homology studies, this strain was found to be similar to Streptomyces stramineus (gene sequence similarity 99 %). The major bioactive metabolite produced by Streptomyces sp. CAH29 isolate was extracted, purified andidentified by nuclear magnetic resonance as tetrangomycin. This known anthraquinone-exhibited antimicrobial activity against Staphylococcus aureus, Streptococcus pyogenes, methicillin resistant Staphylococcus aureus and Candida albicans with inhibition zones of 14, 10, 12 and 8 mm, respectively. Docking results demonstrate that tetrangomycin has a similar mode of action and a comparable docking score to bind to the dehydrosqualene synthase (CrtM) enzyme of methicillin resistant Staphylococcus aureus compared to the current inhibitor. Hence, this suggests that tetrangomycin has a potential to be used as an anti-methicillin resistant Staphylococcus aureus agent. Tetrangomycin also showed moderate free radical scavenging activity with 1,1-diphenyl-2-picryl-hydrazil. Tetrangomycin apparently decreased all of the studied cytokine (pro-inflammatory: interleukin 1B, interleukin 2, tumor necrosis factor and interleukin L6 and anti-inflammatory: interleukin 10) expression levels at IC50 concentrations in A459 (adenocarcinomic human alveolar basal epithelial) and LNCAP (human prostate adenocarcinoma) cell lines. In addition, it reduced Caspase 8 and 3 mRNA levels in LNCAP and A549 cells. This study describes for the first time novel in vitro immunosuppressive function of tetrangomycin by reducing the transcription of cytokine genes. © 2016, Springer Science+Business Media New York.
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- 2016
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17. Modulatory actions of o-coumaric acid on carcinogen-activating cytochrome P450 isozymes and the potential for drug interactions in human hepatocarcinoma cells
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Gulsum Terzioglu, Pelin Atmaca, Alaattin Sen, Sevki Arslan, Gurbet Celik, and Ozden Ozgun
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Carcinoma, Hepatocellular ,Coumaric Acids ,Pharmaceutical Science ,Antineoplastic Agents ,Pharmacology ,Isozyme ,Substrate Specificity ,Activation, Metabolic ,chemistry.chemical_compound ,Cytochrome P-450 Enzyme System ,Drug Discovery ,Humans ,Drug Interactions ,RNA, Messenger ,CYP2C9 ,Carcinogen ,CYP3A4 ,biology ,Dose-Response Relationship, Drug ,Liver Neoplasms ,CYP1A2 ,o-Coumaric acid ,Cytochrome P450 ,General Medicine ,Hep G2 Cells ,CYP2E1 ,eye diseases ,Isoenzymes ,Complementary and alternative medicine ,chemistry ,biology.protein ,Carcinogens ,Molecular Medicine - Abstract
Although humans are exposed to o-coumaric acid (OCA) in their diet, there is no available literature related to drug interaction and the carcinogen-activating potential of OCA in the HepG2 cell line.This study was undertaken to determine the effects of OCA on the cytochrome P450 (CYP) 1A2, CYP2E1, CYP2C9, and CYP3A4 enzymes, which are primarily involved in carcinogen and drug metabolism.The cytotoxicity of OCA in HepG2 cells was investigated by measuring the cleavage of WST-1. The protein and mRNA levels of CYPs were determined by western blotting and RT-PCR, respectively.The EC10, EC25, and EC50 values of OCA were calculated to be 1.84, 3.91 and 7.39 mM, respectively. A sublethal dose of 5 mM was used throughout this study. The CYP1A2 protein and mRNA levels were increased by 52 and 40% (p 0.05), as were the CYP2E1 levels by 225 and 424%, respectively (p 0.05). However, OCA treatment caused 52 and 60% decreases in the levels of CYP3A4 protein and mRNA (p 0.05), respectively. In contrast to CYP3A4, the CYP2C9 protein and mRNA levels increased by 110 and 130%, respectively.Co-administration of OCA with some drugs may lead to undesirable food-drug interactions due to modulatory effects on CYP isozymes involved in drug metabolism. Moreover, exposure to OCA may cause an increase in carcinogenicity and toxicity due to the induction of the CYP isozymes involved in chemical carcinogenesis. Therefore, serious precautions should be taken when using OCA as a supplement.
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- 2015
18. Anti-neuroinflammatory effect of butanolic subextract of Capparis ovata water extract used as an alternative and complementary treatment for multiple sclerosis
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Ozden Ozgun, Alaattin Sen, Gulacti Topcu, Gurbet Celik, Ufuk Kolak, Sevki Arslan, Işıl Hacıbekiroğlu, and TOPÇU, GÜLAÇTI
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Neurology ,Traditional medicine ,Capparis ovata ,Multiple sclerosis ,Immunology ,medicine ,Immunology and Allergy ,Neurology (clinical) ,Biology ,medicine.disease ,Sen A., Topcu G., Ozgun O., Kolak U., Hacibekiroglu I., Celik G., Arslan S., -Anti-neuroinflammatory effect of butanolic subextract of Capparis ovata water extract used as an alternative and complementary treatment for multiple sclerosis-, 12th International Congress of Neuroimmunology (ISNI), Mainz, Almanya, 9 - 13 November 2014, cilt.275, ss.172-173 - Published
- 2014
19. Erratum to 'A Comparative Study for the Evaluation of Two Doses of Ellagic Acid on Hepatic Drug Metabolizing and Antioxidant Enzymes in the Rat'
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Gurbet Celik, Aslı Semiz, Serdar Karakurt, Sevki Arslan, Orhan Adali, and Alaattin Sen
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General Immunology and Microbiology ,lcsh:R ,lcsh:Medicine ,General Medicine ,Erratum ,General Biochemistry, Genetics and Molecular Biology - Published
- 2014
20. Epilobium hirsutum alters xenobiotic metabolizing CYP1A1, CYP2E1, NQO1 and GPx activities, mRNA and protein levels in rats
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Gurbet Celik, Asli Semiz, Alaattin Sen, Serdar Karakurt, Ayse Mine Gencler-Ozkan, and Orhan Adali
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Male ,natural product ,Pharmaceutical Science ,Cytochrome P450 ,Epilobium hirsutum extract ,Epilobium hirsutum ,Pharmacology ,Polymerase Chain Reaction ,chemistry.chemical_compound ,Drug Discovery ,NAD(P)H Dehydrogenase (Quinone) ,rat ,Epilobium ,glutathione peroxidase ,chemistry.chemical_classification ,epilobium hirsutum ,ethoxyresorufin deethylase ,messenger RNA ,Glutathione peroxidase ,Medicinal plant ,article ,Cytochrome P-450 CYP2E1 ,General Medicine ,CYP2E1 ,Onagraceae ,xenobiotic metabolism ,Liver enzymes ,unclassified drug ,enzyme activity ,Blot ,Biochemistry ,Liver ,Molecular Medicine ,NQO1 ,cytochrome P450 1A1 ,Injections, Intraperitoneal ,animal experiment ,Blotting, Western ,Biology ,nadph quinone oxidoreductase 1 ,animal tissue ,Xenobiotics ,in vivo study ,In vivo ,reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) ,drug mechanism ,Cytochrome P-450 CYP1A1 ,Animals ,Animalia ,controlled study ,RNA, Messenger ,Rats, Wistar ,protein expression ,Messenger RNA ,Glutathione Peroxidase ,Drug metabolism ,nonhuman ,Plant Extracts ,Rattus ,animal model ,biology.organism_classification ,Enzyme assay ,oxygenase ,Rats ,enzyme metabolism ,Complementary and alternative medicine ,chemistry ,Gene Expression Regulation ,biology.protein ,liver level ,cytochrome P450 2E1 ,phytochemistry ,Xenobiotic - Abstract
Context: Natural products have attracted increasing interests due to their use in flavoring, nutrition, cosmetics, pharmacy and medicine. Epilobium hirsutum L. (Onagraceae) is known for its analgesic, antimicrobial, and antiproliferative activity. CYP1A1 and CYP2E1, xenobiotic metabolizing enzymes, serve as a metabolic activation route yielding reactive metabolites that are eliminated by the action of NQO1 and glutathione peroxidase (GPx) enzymes. Objective: This study investigated in vivo effects of Epilobium hirsutum (EH) on CYP2E1, CYP1A1, NQO1 and GPx activities, protein and mRNA expressions in liver. Materials and methods: Male Wistar Albino rats were injected with EH at a dose of 37.5mg/kg i.p. daily for 9d. CYP2E1, CYP1A1, NQO1 and GPx activities, protein and mRNA levels were determined by enzyme assays, Western blotting and qPCR, respectively. Results: CYP1A1 associated ethoxyresorufin-O-deethylase activity of control and EH-treated animals were found as 6.54±1.21 and 4.48±1.67nmol/min/mg, respectively. CYP2E1 associated aniline 4-hydroxylase of control and EH group were 0.537±0.011 and 0.109±0.01nmol/min/mg, respectively. However, EH treatment increased the GPx and NQO1 activities from 0.069±0.015 to 0.107±0.026nmol/min/mg and from 163.34±92 to 588.3±14nmol/min/mg, respectively. Furthermore, protein and mRNA expression analysis revealed that CYP1A1 and CYP2E1 levels were decreased while those of NQO1 and GPx increased after EH treatment. Discussion and conclusion: Our current data suggest that the metabolism of xenobiotics, including drugs, may be altered due to changes in the expression and activity of these proteins by EH. © 2013 Informa Healthcare USA, Inc.
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- 2013
21. Investigation of aromotase inhibition by several dietary vegetables in human non-small cell lung cancer cell lines
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Hakan Akca, Alaattin Sen, and Gurbet Celik
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Oncology ,Allium porrum ,Clinical Biochemistry ,Cell ,ved/biology.organism_classification_rank.species ,Biochemistry ,Western blotting ,Non-small cell lung cancer ,Crocus sativus ,Aromatase ,Cytotoxicity ,Crocus sativus and Allium porrum ,messenger RNA ,lung non small cell cancer ,article ,Mentha piperita ,unclassified drug ,Blot ,medicine.anatomical_structure ,Aromatase inhibitors ,Allium porrum extract ,plant extract ,cytotoxicity ,Laurus nobilis ,medicine.medical_specialty ,Biology ,reverse transcription polymerase chain reaction ,Mentha x piperita ,In vivo ,Internal medicine ,medicine ,controlled study ,human ,Crocus sativus extract ,Laurus nobilis extract ,Molecular Biology ,protein expression ,cell viability ,peppermint ,ved/biology ,human cell ,Biochemistry (medical) ,fluorometry ,leek ,Molecular biology ,cell proliferation ,Cell culture ,aromatase inhibitor ,biology.protein - Abstract
Objective: In this study we have investigated the effect of extracts obtained from well-known vegetable diets consumed commonly in Mediterranean and Aegean regions of Turkey on the expression of aromatase at protein, mRNA and activity levels in human non-small cell lung cancer cells- PC-3 and PC-14 cell lines. Method: For this purpose, cytotoxicity was determined by using crystal violet stain. In vivo and in vitro aromatase activity was determined flourometrically. The expression of aromatase in protein and mRNA levels was detected by Western blotting using anti-hCYP19 and reverse transcriptase- polymerase chain reaction using suitable primers, respectively. Result: Extracts obtained from Laurus nobilis, Mentha piperita, Crocus sativus reduced aromatase activity 32%, 44%, 36% and 42%, 32%, 56% in PC-14 and PC-3 cell lines, respectively, no significant changes were observed in protein and mRNA levels. Whereas extract obtained from Allium porrum decreased aromatase activity and mRNA level only in PC-14 cell lines by 52% and 2,5-fold, respectively, without significant influence on aromatase protein level. Conclusion: The results obtained in this study have shown that Laurus nobilis, Mentha piperita, Crocus sativus and Allium porrum do contain effective aromatase inhibitors. Therefore, further studies investigating the content of these vegetables are necessary to understand the potential role and mechanism of action of these foods in reducing the risk of non-small cell lung carcinomas. © TurkJBiochem.com.
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- 2013
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22. Effects of Cyclamen trochopteranthum on hepatic drug-metabolizing enzymes
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Gurbet Celik, Alaattin Sen, Asli Semiz, Ozden Ozgun, Olcay Düşen, Sevki Arslan, and Ramazan Mammadov
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chemistry.chemical_classification ,biology ,Complementary and alternative herbs ,Cyclamen trochopteranthum ,CYP1A2 ,Cytochrome P450 ,Metabolism ,CYP2E1 ,biology.organism_classification ,General Biochemistry, Genetics and Molecular Biology ,Drug interaction potential ,Enzyme ,lcsh:Biology (General) ,chemistry ,Biochemistry ,In vivo ,Toxicity ,biology.protein ,General Agricultural and Biological Sciences ,Drug-metabolizing enzymes ,lcsh:QH301-705.5 ,Cyclamen - Abstract
The modulatory effects of the Cyclamen trochopterantum tuber extract on hepatic drug-metabolizing enzymes, including aniline 4-hydroxylase (A4H; CYP2E1), ethoxyresorufin O-deethylase (EROD; CYP1A), methoxyresorufin O-demethylase (MROD; CYP1A), caffeine N-demethylase (C3ND; CYP1A2) aminopyrene N-demethylase (APND; CYP2C6), and erythromycin N-demethylase (ERND; CYP3A1), were examined in vivo in rats. The activities of all of these enzymes were induced by the cyclamen extract. In addition, Western-blot and RT-PCR results clearly showed that CYP2E1, CYP1A1/CYP1A2 and CYP2C6 protein and mRNA levels were substantially increased by four different doses of cyclamen. Although, the CYP3A1 protein level was increased significantly, the mRNA level was not changed. These results indicate that cyclamen tuber extract might have a potential not only to inhibit and/or induce the metabolism of certain co-administered drugs but also influence the development of toxicity and carcinogenesis due to the induction of the cytochrome P450-dependent drug-metabolizing enzymes.
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- 2011
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