Scopus İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/395
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Article Citation - WoS: 14Citation - Scopus: 15Triterpenoids and Steroids Isolated from Anatolian Capparis Ovata and Their Activity on the Expression of Inflammatory Cytokines(Taylor & Francis Ltd, 2020-01-01) Gazioglu, Isil; Semen, Sevcan; Acar, Ozden Ozgun; Kolak, Ufuk; Sen, Alaattin; Topcu, GulactiContext CapparisL. (Capparaceae) is grown worldwide. Caper has been used in traditional medicine to treat various diseases including rheumatism, kidney, liver, stomach, as well as headache and toothache. Objective To isolate and elucidate of the secondary metabolites of theC. ovataextracts which are responsible for their anti-inflammatory activities. Materials and methods Buds, fruits, flowers, leaves and stems ofC. ovataDesf. was dried, cut to pieces, then ground separately. From their dichloromethane/hexane (1:1) extracts, eight compounds were isolated and their structures were elucidated by NMR, mass spectroscopic techniques. The effects of compounds on the expression of inflammatory cytokines in SH-SY5Y cell lines were examined by qRT-PCR ranging from 4 to 96 mu M. Cell viability was expressed as a percentage of the control, untreated cells. Results This is a first report on isolation of triterpenoids and steroids fromC. ovatawith anti-inflammatory activity. One new triterpenoid ester olean-12-en-3 beta,28-diol, 3 beta-pentacosanoate (1) and two new natural steroids 5 alpha,6 alpha-epoxycholestan-3 beta-ol (5) and 5 beta,6 beta-epoxycholestan-3 beta-ol (6) were elucidated besides known compounds; oleanolic acid (2), ursolic acid (3), beta-sitosterol (4), stigmast-5,22-dien-3 beta-myristate (7) and bismethyl-octylphthalate (8). mRNA expression levels as EC(10)of all the tested seven genes were decreased, particularly CXCL9 (19.36-fold), CXCL10 (8.14-fold), and TNF (18.69) by the treatment of 26 mu M of compound1on SH-SY5Y cells. Discussion and conclusions Triterpenoids and steroids isolated fromC. ovatawere found to be moderate-strong anti-inflammatory compounds. Particularly, compounds1and3were found to be promising therapeutic agents in the treatment of inflammatory and autoimmune diseases.Article Citation - WoS: 31Citation - Scopus: 30Synthesis of Nitrogen-Containing Oleanolic Acid Derivatives as Carbonic Anhydrase and Acetylcholinesterase Inhibitors(Springer Birkhauser, 2023-02-13) Senol, Halil; Turgut, Gurbet Celik; Sen, Alaattin; Saglamtas, Rueya; Tuncay, Salih; Gulcin, Ilhami; Topcu, Guelacti; Çelik Turgut, GurbetIn this study, a total of 13 compounds (5-17) were synthesized starting from oleanolic acid (OA), a natural triterpenoid. Five new compounds (10, 11, 12, 15 and 17), are the main targets of the study, which were synthesized for the first time in this work as oxime, imine and hydrazone derivatives of OA. Other compounds were previously obtained as natural or semi-synthetically. NMR and HRMS analyses were carried out to determine of structures of all the synthesized molecules. The inhibitory effects of the synthesized compounds on acetylcholinesterase (AChE), human carbonic anhydrase I (hCA I) and II (hCA II) were evaluated. Compounds 13 and 15 showed better inhibitory activity than the other compounds against both hCA I and hCA II isoenzymes, which are competing with AZA. In addition, compound 15 showed the strongest AChE inhibitory activity among all the tested compounds, with an IC50 value of 34.46 mu M.Article Citation - Scopus: 23Synthesis and Comprehensive in Vivo Activity Profiling of Olean-12-en-28-ol, 3β-Pentacosanoate in Experimental Autoimmune Encephalomyelitis: A Natural Remyelinating and Anti-Inflammatory Agent(American Chemical Society, 2023-01-04) Şenol, Halil; Ozgun-Acar, Özden; Daǧ, Aydan; Eken, Ahmet; Guner, Hüseyin; Aykut, Zaliha Gamze; Sen, AlaattinMultiple sclerosis (MS) treatment has received much attention, yet there is still no certain cure. We herein investigate the therapeutic effect of olean-12-en-28-ol, 3β-pentacosanoate (OPCA) on a preclinical model of MS. First, OPCA was synthesized semisynthetically and characterized. Then, the mice with MOG<inf>35-55</inf>-induced experimental autoimmune/allergic encephalomyelitis (EAE) were given OPCA along with a reference drug (FTY720). Biochemical, cellular, and molecular analyses were performed in serum and brain tissues to measure anti-inflammatory and neuroprotective responses. OPCA treatment protected EAE-induced changes in mouse brains maintaining blood-brain barrier integrity and preventing inflammation. Moreover, the protein and mRNA levels of MS-related genes such as HLD-DR1, CCL5, TNF-α, IL6, and TGFB1 were significantly reduced in OPCA-treated mouse brains. Notably, the expression of genes, including PLP, MBP, and MAG, involved in the development and structure of myelin was significantly elevated in OPCA-treated EAE. Furthermore, therapeutic OPCA effects included a substantial reduction in pro-inflammatory cytokines in the serum of treated EAE animals. Lastly, following OPCA treatment, the promoter regions for most inflammatory regulators were hypermethylated. These data support that OPCA is a valuable and appealing candidate for human MS treatment since OPCA not only normalizes the pro- and anti-inflammatory immunological bias but also stimulates remyelination in EAE. © 2023 Elsevier B.V., All rights reserved.Article Citation - WoS: 22Citation - Scopus: 26Suppression of Inflammatory Cytokines Expression With Bitter Melon (Momordica Charantia) in TNBS-Instigated Ulcerative Colitis(Sciendo, 2020-09-01) Semiz, Asli; Acar, Ozden Ozgun; Cetin, Hulya; Semiz, Gurkan; Sen, AlaattinBackground and Objective: This study was aimed to elucidate the molecular mechanism of Momordica charantia (MCh), along with a standard drug prednisolone, in a rat model of colitis induced by trinitrobenzene sulfonic acid (TNBS). Methods: After the induction of the experimental colitis, the animals were treated with MCh (4 g/kg/day) for 14 consecutive days by intragastric gavage. The colonic tissue expression levels of C-C motif chemokine ligand 17 (CCL-17), interleukin (IL)-1 beta, IL-6, IL-23, interferon-gamma (IFN-gamma), nuclear factor kappa B (NFkB), and tumor necrosis factor-alpha (TNF-alpha), were determined at both mRNA and protein levels to estimate the effect of MCh. Besides, colonic specimens were analyzed histopathologically after staining with hematoxylin and eosin. Results: The body weights from TNBS-instigated colitis rats were found to be significantly lower than untreated animals. Also, the IFN-gamma, IL-1 beta, IL-6, Il-23, TNF-alpha, CCL-17, and NF-kB mRNA and protein levels were increased significantly from 1.86-4.91-fold and 1.46-5.50-fold, respectively, in the TNBS-instigated colitis group as compared to the control. Both the MCh and prednisolone treatment significantly reduced the bodyweight loss. It also restored the induced colonic tissue levels of IL-1 beta, IL-6, IFN-gamma, and TNF-alpha to normal levels seen in untreated animals. These results were also supported with the histochemical staining of the colonic tissues from both control and treated animals. Conclusion: The presented data strongly suggests that MCh has the anti-inflammatory effect that might be modulated through vitamin D metabolism. It is the right candidate for the treatment of UC as an alternative and complementary therapeutics.Article Citation - WoS: 20Citation - Scopus: 22Role of Cytochrome P450 Polymorphisms and Functions in Development of Ulcerative Colitis(Baishideng Publishing Group inc, 2019-06-21) Sen, Alaattin; Stark, HolgerCytochromes P450s (CYPs) are terminal enzymes in CYP dependent monooxygenases, which constitute a superfamily of enzymes catalysing the metabolism of both endogenous and exogenous substances. One of their main tasks is to facilitate the excretion of these substances and eliminate their toxicities in most phase 1 reactions. Endogenous substrates of CYPs include steroids, bile acids, eicosanoids, cholesterol, vitamin D and neurotransmitters. About 80% of currently used drugs and environmental chemicals comprise exogenous substrates for CYPs. Genetic polymorphisms of CYPs may affect the enzyme functions and have been reported to be associated with various diseases and adverse drug reactions among different populations. In this review, we discuss the role of some critical CYP isoforms (CYP1A1, CYP2D6, CYP2J2, CYP2R1, CYP3A5, CYP3A7, CYP4F3, CYP24A1, CYP26B1 and CYP27B1) in the pathogenesis or aetiology of ulcerative colitis concerning gene polymorphisms. In addition, their significance in metabolism concerning ulcerative colitis in patients is also discussed showing a clear underestimation in genetic studies performed so far.Article Citation - WoS: 16Citation - Scopus: 15Role of AHR, NF-kB and CYP1A1 Crosstalk With the X Protein of Hepatitis B Virus in Hepatocellular Carcinoma Cells(Elsevier, 2023-02) Celik-Turgut, Gurbet; Olmez, Nazmiye; Koc, Tugba; Ozgun-Acar, Ozden; Semiz, Asli; Dodurga, Yavuz; Sen, AlaattinIn 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.Article Citation - WoS: 70Citation - Scopus: 78Prophylactic and Therapeutic Roles of Oleanolic Acid and Its Derivatives in Several Diseases(Baishideng Publishing Group inc, 2020-05-26) Sen, AlaattinOleanolic acid (OA) and its derivatives are widely found in diverse plants and are naturally effective pentacyclic triterpenoid compounds with broad prophylactic and therapeutic roles in various diseases such as ulcerative colitis, multiple sclerosis, metabolic disorders, diabetes, hepatitis and different cancers. This review assembles and presents the latestin vivoreports on the impacts of OA and OA derivatives from various plant sources and the biological mechanisms of OA activities. Thus, this review presents sufficient data proposing that OA and its derivatives are potential alternative and complementary therapies for the treatment and management of several diseases.Article Citation - WoS: 4Citation - Scopus: 4Natural Diterpenoid Alysine a Isolated from Teucrium Alyssifolium Exerts Antidiabetic Effect via Enhanced Glucose Uptake and Suppressed Glucose Absorption(Tubitak Scientific & Technological Research Council Turkey, 2019-10-07) Sen, Alaattin; Ayar, Buket; Yilmaz, Anil; Acar, Ozden Ozgun; Turgut, Gurbet Celik; Topcu, GulactiTeucrium species have been used in folk medicine as antidiabetic, antiinflammatory, antiulcer, and antibacterial agents. We have explored in vitro antidiabetic impacts of 2 natural diterpenoids, alysine A and alysine B, isolated from Teucrium alyssifolium. The lactate dehydrogenase (LDH) cytotoxicity assay, glucose uptake test, glucose utilization (glycogen content) test, glucose transport test, glucose absorption (a-glucosidase activity) test, insulin secretion test, RNA isolation and cDNA synthesis assay, qPCR quantification assays, and statistical analyses were carried out in the present study. Alysine A exerted the following effects at non-cytotoxic doses: Enhanced the glucose uptake, as much as the insulin in the C2C12, HepG2, and 3T3-L1 cells Increased the glycogen content in the C2C12 and HepG2 liver cells, significantly higher than the insulin and metformin Suppressed the alpha-glucosidase and the GLUT2 expression levels in the Caco-2 cells Suppressed the SGLT1 and GLUT1-5 expression levels in the Caco-2 cells Induced the insulin receptor substrate (IRS)1 and GLUT2 expression levels of the BTC6 pancreatic cells Induced the insulin receptor (INSR), IRS2, phosphoinositide 3-kinase (PI3K), GLUT4, and protein kinase (PK) expression levels of the 3T3-L1 and C2C12 cells Increased glucose transport through the Caco-2 cell layer Did not influence insulin secretion in the pancreatic BTC6 cells Consequently, these data strongly emphasized the antidiabetic action of alysine A on the particularly critical model mechanisms that assume a part in glucose homeostasis, such as glucose uptake, utilization, and storage. Moreover, the expression level of the essential genes in glucose metabolism and insulin signaling was altered in a way that the results would be antihyperglycemic. A blend of in vitro and in situ tests affirmed the antihyperglycemic action of alysine A and its mechanism. Alysine A has exercised significant and positive results on the glucose homeostasis; thus, it is a natural and pleiotropic antidiabetic agent. Advanced in vivo studies are required to clarify the impact of this compound on glucose homeostasis completely.Article Citation - WoS: 1Citation - Scopus: 3Complementary Medicines Used in Ulcerative Colitis and Unintended Interactions With Cytochrome P450-Dependent Drug-Metabolizing Enzymes(Tubitak Scientific & Technological Research Council Turkey, 2022-01-01) Sen, AlaattinUlcerative colitis (UC) is an idiopathic, chronic inflammatory disease with multiple genetic and a variety of environmental risk factors. Although current drugs significantly aid in controlling the disease, many people have led to the application of complementary therapies due to the common belief that they are natural and safe, as well as due to the consideration of the side effect of current drugs. Curcumin, cannabinoids, wheatgrass, Boswellia, wormwood and Aloe vera are among the most commonly used complementary medicines in UC. However, these treatments may have adverse and toxic effects due to unintended interactions with drugs or drug-metabolizing enzymes such as cytochrome P450s; thus, being ignorant of these interactions might cause deleterious effects with severe consequences. In addition, the lack of complete and controlled long-term studies with the use of these complementary medicines regarding drug metabolism pose additional risk and unsafety. Thus, this review aims to give an overview of the potential interactions of drug-metabolizing enzymes with the complementary botanical medicines used in UC, drawing attention to possible adverse effects.Article Citation - Scopus: 9Cerium Oxide Nanoparticles Biosynthesized Using Fresh Green Walnut Shell in Microwave Environment and Their Anticancer Effect on Breast Cancer Cells(John Wiley and Sons Inc, 2022-07-12) Sulak, Mine; Turgut, Gurbet Çelik; Sen, AlaattinIn 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-κB 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-κB 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-κB-mediated transcription. © 2022 Elsevier B.V., All rights reserved.