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Öğe Anticancer, Antioxidant, Antimicrobial and Enzyme Inhibitory Activities of Inula aucheriana(Kahramanmaras Sutcu Imam Univ Rektorlugu, 2022) Guclu, Gulsen; Ergul, Merve; Ucar, Esra; Eruygur, Nuraniye; Atas, Mehmet; Akpulat, Huseyin AskinThe Inula aucheriana, of the Asteraceae family, is widespread in Turkey. The aim of this study was to investigate different biological properties and thereby reveal the pharmacological potential of this plant, which is already known to be used in the treatment of various diseases,. Following the preparation of 80% ethanol extract from I. aucheriana, qualitative and quantitative methods were used to investigate the chemical composition (Q-TOF analysis), antioxidant (spectrophotometric analysis), inhibitory enzyme (Ellman's method), antimicrobial (MIC concentration value), and anti-cancer (XTT analysis) activities. The results showed that 80% ethanol extract from I. aucheriana was a potent antioxidant, with anti-cancer and enzyme inhibitor effects. In the chemical composition analysis, the primary compound of the extract was determined to be luteolin (32.55%). I. aucheriana extract was seen to have AChE and BChE inhibition, , and when compared with the reference drug, the extract was determined to have an inhibitory effect an enzyme called alpha-glucosidase. Besides, relatively high tyrosinase enzyme inhibition was also detected. The extract significantly showed antiproliferative activity on the MDA-MB-231 cells at 0.0625 mg/mL and higher concentrations,for 24 hours in a a dose-dependent manner.This study is the first to evaluate enzyme inhibitory effect and antioxidant activity of I. aucheriana.Öğe Design, synthesis, and anticancer activity of novel 4-thiazolidinone-phenylaminopyrimidine hybrids(Springer, 2021) Ture, Asli; Ergul, Mustafa; Ergul, Merve; Altun, Ahmet; Kucukguzel, Ilkay4-Thiazolidinones and phenylaminopyrimidines are known as anticancer agents. Imatinib is the pioneer phenylaminopyrimidine derivative kinase inhibitor, which is used for the treatment of chronic myeloid leukemia. With a hybrid approach, a novel series of 5-benzylidene-2-arylimino-4-thiazolidinone derivatives containing phenylaminopyrimidine core were designed, synthesized, and tested for their anticancer activity on K562 (chronic myeloid leukemia), PC3 (prostat cancer), and SHSY-5Y (neuroblastoma) cells. Since superior anticancer activity was observed on K562 cells, further biological studies of selected compounds (8, 15, and 34) were performed on K562 cells. For the synthesis of designed compounds, thiourea compounds were converted to 2-imino-1,3-thiazolidin-4-ones with alpha-chloroacetic acid in the presence of sodium acetate. 5-Benzylidene-2-imino-1,3-thiazolidin-4-one derivatives were obtained by Knoevenagel condensation of 2-imino-1,3-thiazolidin-4-ones with related aldehydes. Compounds 8, 15, and 34 were evaluated for cell viability, apoptosis studies, cell cycle experiments, and DNA damage assays. IC50 values of compounds 8, 15, and 34 were found as 5.26 +/- 1.03, 3.52 +/- 0.91, and 8.16 +/- 1.27 mu M, respectively, in K562 cells. Preferably, these compounds showed less toxicity towards L929 cells compared to imatinib. Furthermore, compounds 8 and 15 significantly induced early and late apoptosis in a time-dependent manner. Compounds 15 and 34 induced cell cycle arrest at G0/G1 phase and compound 8 caused cell cycle arrest at G2/M phase. Based on DNA damage assay, compounds 8 and 15 were found to be more genotoxic than imatinib towards K562 cells. To put more molecular insight, possible Abl inhibition mechanisms of most active compounds were predicted by molecular docking studies. In conclusion, a novel series of 5-benzylidene-2-arylimino-4-thiazolidinone derivatives and their promising anticancer activities were reported herein. [GRAPHICS] .Öğe Determination of biological activity of Tragopogon porrifolius and Polygonum cognatum consumed intensively by people in Sivas(Elsevier, 2020) Eruygur, Nuraniye; Ucar, Esra; Atas, Mehmet; Ergul, Merve; Ergul, Mustafa; Sozmen, FazliObjective: This study was aimed to investigate the in vitro antioxidant, antimicrobial, cytotoxicity, and enzyme inhibition activities of Tragopogon porrifolius and Polygonum cognatum which are naturally grown and consumed intensively by people in Sivas, Turkey. Methods: Plant materials were extracted with aqueous ethanol by maceration method. The components of the extracts were determined using the Gas Chromatography Mass Spectrometry. Antimicrobial, cytotoxic and enzyme inhibition activities of the extracts were investigated by micro dilution, XTT assay and 96-micro-well plate methods, respectively. The antioxidant activity evaluated using the DPPH radical scavenging, thiobarbituric acid and reducing power methods. The total phenol and total flavonoid content was also examined. Results: GC-MS analysis revealed the presence of 31 compounds inP. cognatum extract and 29 compounds in T. porrifolius extract. According to the results, T. porrifolius extract showed high level of antioxidant activity in comparison to P. Cognatum extract. T. porrifolius exhibited higher alpha-glucosidase inhibitory activity, and both extract showed strong alpha-amylase inhibition activity compared to reference drug acarbose. T. porrifolius and P. cognatum ethanolic extracts exhibited antimicrobial activity in the concentration range of 0.039-2.5 mg/ml. Both extracts also exhibited significant anticancer effect on MDA-MB-231 breast cancer cells. The IC50 values of T. porrifolius and P. cognatum extracts in MDA-MB-231 cells were determined as 0.0625 mg/mL and 0.053 mg/mL, respectively. Conclusion: Our findings demonstrated that T. porrifolius and P. cognatum ethanolic extracts have promising effect on antioxidant, antimicrobial and cytotoxic activity as well as enzyme inhibition activity, and hence further studies required to identify specific compounds responsible for these activities.Öğe Determination of inhibitory activities of enzymes, related to Alzheimer's disease and diabetes mellitus of plane tree (Platanus orientalis L.) extracts and their antioxidant, antimicrobial and anticancer activities(C M B ASSOC, 2018) Ucar, Esra; Eruygur, Nuraniye; Atas, Mehmet; Ergul, Merve; Ergul, Mustafa; Sozmen, FazliPlane tree (Platanus orientalis L.) leaves have been employed for centuries in various countries due to their pharmacological value. Therefore, determination of the biological activity of the leaves is of interest. The aim of the study was to evaluate the inhibitory effects against Alzheimer's disease-related enzymes Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE), diabetes mellitus related enzymes alpha-glucosidase and alpha-amylase. The antioxidant, anticancer, and antimicrobial activities of the leaves were also studied. According to the results, both water and methanol extracts of P. orientalis demonstrated more alpha-glucosidase and alpha-amylase inhibition activity than the antidiabetic drug-acarbose at the same concentration level. In addition, extracts showed good inhibition activity against AChE and BuChE. Significant results were obtained regarding antioxidant, anticancer, and antimicrobial activities. These results are very promising especially for the improvement of pharmaceutical formulations to treat various diseases such as age-related diseases, cancer, diabetes etc. and it is necessary to conduct further experiments.Öğe Evaluation of potential cytotoxic and apoptotic effects of bioymifi on human multiple myeloma cell lines(Pharmacotherapy Group, 2020) Terzi, Hatice; Ergul, MervePurpose: To investigate the cytotoxic and apoptotic activities of bioymifi (DR5 agonist) on bortezomibsensitive and bortezomib-resistant cells. Methods: The cytotoxic activities of bioymifi against bortezomib-sensitive (U266) and bortezomib-resistant (U266/BR) cells were evaluated using XTT cell viability test. The cells were exposed to increasing concentrations of bioymifi for 24 h. Cell cycle analysis was performed while apoptosis was examined by flow cytometry. Results: Bioymifi showed significant cytotoxic effects on 0266 and U266/BR in a concentration-dependent manner (p < 0.05). The IC50 values of bioymifi in U266 and U266/BR cells were 10.4 and 20.9 mu M, respectively. Moreover, when compared to the untreated cells, bioymifi treatment at IC50 concentrations considerably increased the percentage of apoptotic cells. Bioymifi treatment also caused cell cycle arrest at the G2/M phase in both cell types. Conclusion: The results show that bioymifi is a promising candidate for multiple myeloma treatment. However, further studies are required to evaluate the clinical anticancer activity of this agent.Öğe Evaluation of Various Biological Activities of Endemic Sideritis libanotica Extracts(Horticulture and Forestry Society from Transylvania, 2019) Atas, Mehmet; Eruygur, Nuraniye; Sozmen, Fazli; Ergul, Mustafa; Ergul, Merve; Akpulat, Huseyin Askin; Ucar, EsraIn recent years, using of plants to develop combine therapies for treatment of certain diseases such as cancer, Alzheimer's disease, and diabetes mellitus is extremely plausible approach. Perhaps, the definitive treatment of some of these diseases is hidden in the complex content of a plant in nature. Thus, in the present study, we decided to determine the biological activities of methanol and water extracts of the endemic Sideritis libanotica. To the best of our knowledge, the present study is the first investigation on antioxidant, enzyme inhibitory activity, antimicrobial activity, and in vitro cytotoxicity of S. libanotica. According to results, while the methanol extract shows better anti-cholinesterase, ?-glucosidase, and ?-amylase inhibition activity and cytotoxicity than the water extract, the tyrosinase inhibitory activity of the water extract was found to be better than the methanol extract. This study provides valuable information on how the biological activity of endemic S. libanotica changes in different solvent extractions such as water and methanol. © 2019, Horticulture and Forestry Society from Transylvania. All rights reserved.Öğe Important Anti-Cancer Applications of Protein Based Nanoparticles(BENTHAM SCIENCE PUBL LTD, 2013) Ergul, Mustafa; Ergul, Merve; Tutar, YusufCancer is one of the most important health problems in the world and the treatment approaches are still challenging and generally not at desirable levels. Conventional anti-cancer agents may cause systemic toxicity, have poor solubility, and lack of selectivity. In order to overcome these hurdles, nanoparticle based therapeutics have been widely employed to enhance therapeutic efficacies and reduce systemic toxicity of pharmaceutical agents. In recent years, nanoparticulate carrier systems (NPCs) in medicine have attracted considerable scientific attention and interest in the worldwide because of their unique properties in the diagnosis and therapy of many diseases including cancer. One of the therapeutic strategies of NPCs is protein based nanoparticles. Human serum albumin (HSA) and bovine serum albumin (BSA) are the most frequently used materials for this purpose due to their remarkable advantages. In this review article, we focused on protein based nanoparticles and summarized their important applications including anti-cancer drug delivery, photodynamic therapy, and gene delivery.Öğe IN VITRO ANTIOXIDANT, ANTIMICROBIAL, ANTICANCER ACTIVITIES ASSESSMENT OF THYMUS PECTINATUS, SCREENING OF ENZYME INHIBITORY(Parlar Scientific Publications (P S P), 2021) Ergul, Merve; Guclu, Gulsen; Atas, Mehmet; Cetin, Metin Durmus; Eruygur, Nuraniye; Ucar, Esra; Akpulat, Huseyin AskinAccording to the data obtained in this study, Thymus pectinatus has antioxidant and enzyme inhibitory activities while has not showed antimicrobial activities. The results of the current study provide valuable information, showing that the major component of the water extract of T. pectinatus is 1,3-Propanediol, 2 -methyl-, dipropanoate (59.34 %). This is the first investigation of the antioxidant and enzyme inhibitory activity of T. pectinatus. The results showed that the water extract had high antioxidant, anti-amylase, and anticancer effects, and a higher total phenolic content. Therefore, further phytochemical and bioactivity-guided isolation of T. pectinatus water extract could be carried out to identify the active compounds.Öğe In vitro comparison of the cytotoxic effects of lenalidomide alone and in combination with verapamil on myeloma cell line(Wolters Kluwer Medknow Publications, 2021) Tastemur, Seyma; Sencan, Mehmet; Terzi, Hatice; Ergul, Merve; Tastemur, MercanIntroduction Multiple myeloma (MM) is a malignant hematological disease characterized by monoclonal proliferation of plasma cells. High-dose chemotherapy with novel agents and autologous stem cell transplantation are options for treatment. However, MM treatment generally results in failure. The most important reason for this failure is the resistance to chemotherapeutic drugs. Various studies have been tried to combine chemosensitizer agents that increase the cytotoxic effects of the chemotherapeutics to eliminate the drug resistance. In our study, we aimed to evaluate the effect of verapamil on the cytotoxic effect of lenalidomide on the myeloma cell line. Materials and methods Verapamil is a chemosensitizer that suppresses the P-glycoprotein. In our study, lenalidomide, an immunomodulatory agent, was compared alone and in combination with verapamil for cytotoxic effects. U266 MM cell line was used in the study. At the concentrations of 0.001, 0.01, 0.1, 1, 10, 50, and 100 mu M, lenalidomide alone and the combination of lenalidomide at the same concentrations with 2.5 mu g/ml of verapamil were compared in terms of possible cytotoxic properties. Cell viability was measured by XTT (2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide) test. Results A statistically significant decrease in the inhibitor concentration, causing 50% decrease in cell proliferation (IC50) of lenalidomide, was provided via verapamil administration. Our study revealed that the cytotoxic effect of lenalidomide increases when combined with verapamil. Conclusion We aimed to understand whether the cytotoxic effect of lenalidomide, which has an important place in the treatment of MM, can be increased with an easily available drug such as verapamil. We think that more studies and meta-analyses are needed owing to the different results related to the subject in the literature, and we hope to set an example for new studies. (C) 2021 The Egyptian Journal of HaematologyÖğe In Vitro Evaluation of the Chemical Composition and Various Biological Activities of Ficus carica Leaf Extracts(Turkish Pharmacists Assoc, 2019) Ergul, Mustafa; Ergul, Merve; Eruygur, Nuraniye; Atas, Mehmet; Ucar, EsraObjectives: The present study aimed to investigate the inhibitory activities of enzymes related to diabetes mellitus and Alzheimer's disease of the methanol and water extracts of Ficus carica leaf extracts. The bioactive compounds and anticancer, antioxidant, and antimicrobial effects of the extracts were also investigated. Materials and Methods: The bioactive compounds in the extracts were determined by gas chromatography-mass spectrometry. The antioxidant activity was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6 sulphonic acid) (ABTS) radical scavenging, total phenol and flavonoid content, ferric reducing power, and iron chelating method. The anticancer, anticholinesterase, and antimicrobial effects were investigated using the XTT assay, Ellman method, and microdilution, respectively. Results: Our results showed that between the water and methanol extracts there was a difference in terms of chemical composition. The antioxidant results suggested that both extracts have strong antioxidant activity. Similarly, both extracts showed strong alpha-glucosidase and alpha-amylase inhibition activity, while the water extract had higher inhibition activity than the methanol extract against acetylcholinesterase and butyrylcholinesterase. The methanol extract of F. carica exhibited significant anticancer activity on MDA-MB-231 cells and showed moderate antimicrobial activities against Escherichia coli and Staphylococcus aureus. Conclusion: Our results suggest that F. carica leaves could be a valuable source for developing a promising therapeutic agent in cancer, diabetes, and Alzheimer's disease.Öğe Investigating the effects of the Rho-kinase enzyme inhibitors AS1892802 and fasudil hydrochloride on the contractions of isolated pregnant rat myometrium(ELSEVIER SCIENCE BV, 2016) Ergul, Merve; Turgut, Nergiz H.; Sarac, Bulent; Altun, Ahmet; Yildirim, Sahin; Bagcivan, IhsanObjectives: Rho-kinases (ROCKs), are one of the dynamic structures of the actin cytoskeleton and they mediate different biological processes, including regulation of calcium sensitivity of smooth muscle contraction. The activation of Rho A/ROCK system is thought to be effective on the termination time of the pregnancy process. The aim of this study, was to investigate in vitro effects of the ROCK enzyme inhibitors, clinically available fasudil hydrochloride, and a new promising inhibitor AS1892802, on the contractions of isolated pregnant rat myometrium. Study design: Term pregnant Wistar albino rats (n = 12), weighing 200-220 g, were used in this study. Myometrial tissues obtained from rats were dissected into four full-thickness longitudinal muscle strips and then myometrial tension was recorded isometrically. The inhibitory effects of cumulative concentrations of AS1892802 and of fasudil hydrochloride in the presence and absence of ODQ (guanylate cyclase inhibitor), L-NAME (nitric oxide synthase inhibitor) and L-NNA (endothelial nitric oxide synthase inhibitor) on oxytocin-induced myometrial contractions were measured, and values for -log10 EC50 (pD(2)) and mean maximal inhibition (E-max) were compared. Results: Both ROCK inhibitors, AS1892802 and fasudil hydrochloride starting from the concentrations of 10(-6) M reached statistical significance on contraction amplitude and frequency of myometrial strips (p < 0.05). The inhibition of the amplitude and frequency of myometrial contractions was antagonized with ODQ (10(-5) M; only amplitude), L-NAME (3 x 10(-5) M) and L-NNA (10(-5) M) (p < 0.05). Conclusion: These results suggest that fasudil hydrochloride and AS1892802 may contribute to the development of new tocolytic drugs. We conclude that AS1892802 and fasudil hydrochloride perform this inhibitory effect partially through ROCK inhibition and the NO/cGMP pathway. (C) 2016 Elsevier Ireland Ltd. All rights reserved.Öğe Positive effects of angiotensin-converting enzyme (ACE) inhibitor, captopril, on pentylenetetrazole-induced epileptic seizures in mice(Pharmacotherapy Group, 2020) Tastemur, Yasar; Gumus, Erkan; Ergul, Merve; Ulu, Mustafa; Akkaya, Recep; Ozturk, Aysegul; Taskiran, Ahmet SevkiPurpose: To evaluate the effects of an angiotensin-converting enzyme (ACE) inhibitor, captopril, on pentylenetetrazole (PTZ)-induced seizures and post-seizure hippocampal injury. Materials: Thirty-five male Balb-c mice weighing 30 - 33 g were divided into control, saline PTZ, s(erum ;physiologic 1 ml/kg as solvent), positive control (valproic acid 200 mg/kg), captopril (25 mg/kg/day for 7 days), and captopril (50 mg/kg/ day for 7 days) groups. PTZ (60 mg/kg) was administered thirty minutes after medication administration to induce epileptic seizures. The animals were observed for 30 min to record Racine stages, the time of the first myoclonic jerk (FMJ), and the occurrence of the first generalized tonic-clonic seizure (GTCS). Cornu Ammonis (CA)1, CA2, CA3, and the dentate gyrus (DG) of the hippocampus underwent histopathological examinations. The levels of total oxidant status (TOS), oxidative stress markers (total antioxidant status, TAS), and oxidative stress index (OSI) were measured in the brain tissue. Results: Compared to PTZ group, 25 mg/kg captopril decreased seizure scores and delayed FMJ and GTCS (p < 0.05). Histopathological assessment demonstrated that both 25 and 50 mg/kg captopril alleviated neuronal injury in CA1, CA2, CA3, and DG compared to PTZ (p < 0.05). Also, TOS and OSI levels in the brain tissue were reduced by both 25 and 50 mg/kg doses of captopril (p < 0.05). Conclusion: Captopril favorably improves epileptic seizure parameters and acts against post-seizure neuronal injury in the hippocampus. Captopril may be a drug of choice in epileptic individuals with hypertension.Öğe Proteasome Inhibitor Carfilzomib Enhances the Anticancer Effect of Paclitaxel in MDA-MB-231 Breast Cancer Cells(Indian Pharmaceutical Assoc, 2019) Terzi, Hatice; Mustafa, E.; Ergul, Merve; Ahmet, A.; Mehmet, S.y This study was aimed to determine the anticancer efficacy of the combination of paclitaxel, the standard treatment of breast cancer, and carfilzomib, which is a proteasome inhibitor, in breast cancer cells in vitro. Paclitaxel, carfilzomib and their combinations at various concentrations were added to MDA-MB-231 human breast cancer cells, and cell viability was detected using the XTT assay. Combination index values were determined using the Chou-Talalay method. Apoptotic effect and cell cycle arrest of single administrations and combinations of these agents were also evaluated using the flow cytometry. According to the results of the XTT assay, the combination produced a greater anticancer effect than that produced by both agents administered alone. Chou-Talalay approaches exhibited that the combination of paclitaxel and carfilzomib demonstrated a synergistic effect. The flow analysis showed that the combinations have induced a cell cycle arrest of MDA-MB-231 cells at G2/M phase and significantly induced apoptosis. The present study revealed that carfilzomib could significantly increase the efficacy of paclitaxel in human breast cancer cells in vitro. It is recommended that carfilzomib to be used along with paclitaxel in metastatic breast cancer patients to increase the anticancer effect and reduce potential toxicity-related side effects.Öğe The effect of salmon calcitonin against glutamate-induced cytotoxicity in the C6 cell line and the roles the inflammatory and nitric oxide pathways play(Springer/Plenum Publishers, 2021) Taskiran, Ahmet Sevki; Ergul, MerveRecent evidence has shown that salmon calcitonin (sCT) has positive effects on the nervous system. However, its effect and mechanisms on glutamate-induced cytotoxicity are still unclear. The current experiment was designed to examine the effect of sCT on glutamate-induced cytotoxicity in C6 cells, involving the inflammatory and nitric oxide stress pathways. The study used the C6 glioma cell line. Four cell groups were prepared to evaluate the effect of sCT on glutamate-induced cytotoxicity. The control group was without any treatment. Cells in the glutamate group were treated with 10 mM glutamate for 24 h. Cells in the sCT group were treated with various concentrations (3, 6, 12, 25, and 50 mu g/mL) of sCT for 24 h. Cells in the sCT + glutamate group were pre-treated with various concentrations of sCT for 1 h and then exposed to glutamate for 24 h. The cell viability was evaluated with an XTT assay. Nuclear factor kappa b (NF-kB), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), neuronal nitric oxide synthase (nNOS), nitric oxide (NO), cyclic guanosine monophosphate (cGMP), caspase-3, and caspase-9 levels in the cells were measured by ELISA kits. Apoptosis was detected by flow cytometry method. sCT at all concentrations significantly improved the cell viability in C6 cells after glutamate-induced cytotoxicity (p < 0.001). Moreover, sCT significantly reduced the levels of NF-kB (p < 0.001), TNF-alpha, and IL-6 levels (p < 0.001). sCT also decreased nNOS, NO, and cGMP levels (P < 0.001). Furthermore, it decreased the apoptosis rate and increased the live-cell rate in the flow cytometry (P < 0.001). In conclusion, sCT has protective effects on glutamate-induced cytotoxicity in C6 glial cells by inhibiting inflammatory and nitric oxide pathways. sCT could be a useful supportive agent for people with neurodegenerative symptoms.Öğe Thiamine Protects Glioblastoma Cells against Glutamate Toxicity by Suppressing Oxidative/Endoplasmic Reticulum Stress(Pharmaceutical Soc Japan, 2021) Ergul, Merve; Taskiran, Ahmet SevkiThiamine (vitamin B1), which is synthesized only in bacteria, fungi and plants and which humans should take with diet, participates in basic biochemical and physiological processes in a versatile way and its deficiency is associated with neurological problems accompanied by cognitive dysfunctions. The rat glioblastoma (C6) model was used, which was exposed to a limited environment and toxicity with glutamate. The cells were stressed by exposure to glutamate in the presence and absence of thiamine. The difference in cell proliferation was evaluated in the XTT assay. Oxidative stress (OS) markers malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels, as well as endoplasmic reticulum (ER) stress markers 78-kDa glucose-regulated protein (GRP78), activating transcription factor-4 (ATF-4), and C/EBP homologous protein (CHOP) levels, were measured with commercial kits. Apoptosis determined by flow cytometry was confirmed by 4',6-diamidino-2-phenylindole (DAPI) staining. At all concentrations, thiamine protects the cells and increased the viability against glutamate-induced toxicity. Thiamine also significantly decreased the levels of MDA, while increasing SOD and CAT levels. Moreover, thiamine reduced ER stress proteins' levels. Moreover, it lessened the apoptotic cell amount and enhanced the live-cell percentage in the flow cytometry and DAPI staining. As a result, thiamine may be beneficial nutritional support for individuals with a predisposition to neurodegenerative disorders due to its protective effect on glutamate cytotoxicity in glioblastoma cells by suppressing OS and ER stress.
