Şen, Alaattin

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Main Affiliation:01. Abdullah Gül University
Status: Former Staff
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Sen, Alaattin
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  • Article
    Citation - WoS: 22
    Citation - Scopus: 25
    Role of Cytochrome P450 Polymorphisms and Functions in Development of Ulcerative Colitis
    (Baishideng Publishing Group inc, 2019-06-21) Sen, Alaattin; Stark, Holger
    Cytochromes 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: 4
    Citation - Scopus: 3
    Neuroinflammatory Human Brain Organoids Enable Comprehensive Drug Screening Studies: Fingolimod and Its Analogues in Focus
    (Bentham Science Publishing Ltd, 2026) Acar, Busra; Pepe, Nihan Aktas; Zivkovic, Aleksandra; Stark, Holger; Sen, Alaattin
    Introduction The absence of physiologically relevant models for neuroinflammatory brain disorders, such as multiple sclerosis (MS), highlights the need for improved drug screening platforms. To bridge this gap, this study aimed to develop a human brain organoid (hBO) model incorporating essential neural cell types, including astrocytes, microglia, and oligodendrocytes.Methods hBOs were generated from H9 stem cells, and neuroinflammatory characteristics were elicited by lipopolysaccharide (LPS). The expression of specific neuronal and inflammatory markers was assessed through qRT-PCR, immunofluorescence staining (IFS), and ELISA.Results IFS of mature hBOs with anti-SOX2, anti-SATB2, anti-MAPT, anti-GFAP, anti-MBP, and anti-IBA1 antibodies and images collected with the confocal microscope confirmed the differentiation of H9 cells into cortical neurons, astrocytes, microglia, and oligodendrocyte cell types. Elevated GFAP, IBA1, NF-kappa B, and IL-6 levels, along with reduced CNPase expression with LPS treatment, were considered reflective of MS-like pathology and were used to test fingolimod and its derivatives. Fingolimod and all its derivatives, specifically ST-1505, decreased MAPT (2.1-fold in ELISA, 1.7-fold in IFS), GFAP (1.8-fold in IFS), TNF alpha (5.4-fold in qRT-PCR), and FABP (1.5-fold in ELISA) levels, and increased IL-10 (11-fold in qRT-PCR) and MBP (2.9-fold in IFS) levels.Discussion The present data collectively showed LPS to evoke neuroinflammation in the hBO model, while fingolimod and its derivatives, particularly ST-1505, exhibited significant anti-inflammatory and neuroprotective properties by counteracting these evoked changes in the hBO model.Conclusion The findings supported the applicability of brain organoids as a model system for drug screening studies for neuroinflammatory brain diseases.
  • Article
    Citation - WoS: 2
    Citation - Scopus: 5
    Complementary Medicines Used in Ulcerative Colitis and Unintended Interactions With Cytochrome P450-Dependent Drug-Metabolizing Enzymes
    (Tubitak Scientific & Technological Research Council Turkey, 2022) Sen, Alaattin
    Ulcerative 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 - WoS: 16
    Citation - Scopus: 17
    Triterpenoids 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, Gulacti
    Context 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: 7
    Citation - Scopus: 7
    Cinnamomum Zeylanicum Extract Incorporated Electrospun Poly(Lactic Acid)/ Gelatin Membrane as a New Wound Dressing
    (Elsevier, 2025) Tarhan, Seray Zora; Pepe, Nihan Aktas; Sen, Alaattin; Isoglu, Ismail Alper
    In this study, we fabricated poly(lactic acid)/gelatin electrospun membranes containing various concentrations of Cinnamomum zeylanicum extract and evaluated them as a novel wound dressing. The electrospun membranes were chemically, morphologically, and mechanically characterized, and the results were discussed in comparison with the literature. Electrospun membranes' biodegradability, swelling, and release properties were evaluated, with the CE7.5 membrane having values of 29.60 f 7.20 and 542.1 f 48.3 % and 66.9 %, respectively. Antibacterial activity was observed in CE7.5 and CE10 membranes against E. coli and S. aureus strains. At the highest concentration (CE10), 111.7 f 5.6 % and 96 f 12.375 % cell viability were detected in fibroblasts and differentiated LPS-induced THP-1 cells. Cell viability was further evaluated by Annexin-V/PI staining, revealing that 97.95 f 1.63 % of the cells remained viable in the CE7.5-treated membranes, while only 1.85 f 1.49 % of necrotic cells were detected in the treated cell population. Fibroblasts treated with the CE7.5 membrane showed a 42 % improvement in wound closure compared to non-treated cells. The anti-inflammatory properties of the electrospun membranes were also investigated. Treatment with the conditioned CE7.5 membrane downregulated Tba1 and tau proteins by 45.1 and 51.055 %, respectively. This study concluded that the newly developed Cinnamomum zeylanicum extract incorporated poly(lactic acid)/gelatin electrospun membranes could be a promising wound dressing material.
  • Article
    Apatinib Sensitizes Human Breast Cancer Cells Against Navitoclax and Venetoclax Despite Up-Regulated Bcl-2 and Mcl-1 Gene Expressions
    (Kare Publ, 2021) Kavakcioglu Yardimci, Berna; Ozgun Acar, Ozden; Semiz, Asli; Sen, Alaattin; Acar, Ozden Ozgun; Yardımcı, Berna Kavakcıoğlu
    OBJECTIVE Defects in apoptotic cell death which restrict the success of conventional cytotoxic therapies have pivotal roles in a number of pathological conditions including cancer. However, a novel drug class targeting pro-survival Bcl-2 protein family members has been developed with the understanding of the structures and interactions of Bcl-2 proteins. Within this new class, Bcl-2/Bcl-xL inhibitor Navitoclax and Bcl-2 specific inhibitor Venetoclax have been shown to demonstrate strong anticancer activities on several types of cancers. But their low affinity to other anti-apoptotic proteins limits their clinical usage. Here, we investigated the cytotoxic and apoptotic effects of Navitoclax/Venetoclax and their combinations with specific tyrosine kinase inhibitor Apatinib on estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 breast cancer cell lines. METHODS MTT assay was used for the evaluation of the inhibition of cancer cell proliferation. ELISA test and Quantitative real-time PCR assay was performed to determine the role of caspase-3, Bak, Bax, Bcl-2, Bcl-xL and Mcl-1 proteins in the inhibition of cell proliferation triggered by the tested agents. RESULTS We found that aggressive MDA-MB-231 cell line was more sensitive to all tested agents. Apatinib significantly enhanced Navitoclax/Venetoclax mediated inhibition of cell viability in both cancer cell lines despite up-regulation in the expression levels of Bcl-2 and Mcl-1 genes. We further demonstrated significant Bak/Bax and caspase-3 expression in less aggressive MCF-7 cells. CONCLUSION Our findings have impacts on Navitoclax/Venetoclax plus Apatinib based therapy for breast adenocarcinoma. On the other hand, further studies should be conducted to elucidate the mechanisms underlying synergistic effects of Navitoclax/Venetoclax plus Apatinib combinations.
  • Article
    Citation - WoS: 1
    Citation - Scopus: 1
    Interaction of Inula Viscosa (L.) Aiton with IBA1 via Rosmarinic Acid and Rutin: Insights from Computational Models and Biological Effects
    (Wiley-VCH verlag GmbH, 2025) Aktas Pepe, Nihan; Acar, Busra; Ceylan Ekiz, Yagmur; Senol, Ayse Merve; Semiz, Gurkan; Sen, Alaattin; Celik Turgut, Gurbet
    Inula viscosa (L.) Aiton is a traditional medicinal plant extensively utilized in Mediterranean nations for the treatment of rheumatic pain, inflammatory disorders, diabetes, anemia, and cancer. This study further explored its anti-inflammatory mechanisms through the highest components, chlorogenic acid, rosmarinic acid, and rutin, on the expression of the ionized calcium-binding adapter molecule 1 (Iba1) on monocyte-derived macrophage-like cells. Iba1 is known to contribute pathogenesis of diverse inflammatory diseases. HPLC analysis identified 13 major phenolic compounds, with rosmarinic acid, chlorogenic acid, and rutin as major components. The aqueous extract of the plant and its major components exhibited dose-dependent antiproliferative activity on pTHP-1, RAW264.7, and PCS-201-012 cells. Immunofluorescence staining revealed a significant reduction in Iba1 protein expression, which is associated with inflammation, at the high dose of I. viscosa and rutin. Molecular docking studies indicated that rosmarinic acid and rutin had the strongest predicted interactions with Iba1, with docking scores of -12.403 and -12.301 kcal/mol and MM/GBSA binding energies of -64.47 and -84.20 kcal/mol, respectively. I. visoca and its major components were observed to significantly suppress iNOS activity in LPS-stimulated cells; these findings were also supported by RT-PCR results. Treatment with the high dose of I. viscosa resulted in 9.45% necrotic cells and caused cell cycle arrest in the S phase (59.2 +/- 5.23%). This suggests that it may potentially reduce the proliferation of activated macrophages. In the fibroblast migration assays, the relative wound closure rate was found to be significant 27.06 +/- 18.09% at the low dose of I. viscosa and 31.59 +/- 22.42% at the high dose of I. viscosa. Although the relatively low wound closure rate limits tissue repair, it may benefit chronic wounds and fibrosis by suppressing excessive cell proliferation and inflammation. These results suggest that I. viscosa is a promising natural source of bioactive compounds with potential applications in anti-inflammatory drug development.
  • Doctoral Thesis
    Uzun Kodlanmayan rna X-Inaktif Spesifik Transkriptin (XIST) Beyin Organoidlerinde Nöroinflamasyon ve Miyelinleşmedeki Rolü
    (2025) Pepe, Nihan Aktaş; Şen, Alaattin; Güner, Şerife Ayaz
    X-inaktif spesifik transcript (XIST) nöroinflamasyonda rol oynayan faktörlerden biridir. Bu çalışmada XIST'nin nöronal farklılaşmada, nöroinflamasyonda, miyelinasyonda, ve terapötik cevaptaki rolü ve sonuç olarak Multipl Skleroz (MS) patojenezindeki etkisi insan serebral organoidlerinde incelenmiştir. XIST susturulmuş H9 hücrelerinden elde edilen oligodendrosit içeren insan serebral organoidler FTY720 veya DMF ile muamele edilmiştir. XIST susturulmuş grupta nöronal kök hücre, eksitatör nöron, mikroglia ve olgun oligodendrosit belirteçlerinde iki kat artış belirlenmiştir. Bununla birlikte, XIST susturulması IL-10 mRNA seviyelerini 2 kata kadar artırırken, MBP ve PLP1 seviyelerini 2,3 ve 0,6 kat etkilemiştir. XIST susturulmuş dokularda Iba1 protein ifadesi üçe katlanırken, MBP'de herhangi bir artış gözlenmemiştir. Son olarak XIST susturulmuş dokularda alfa-sinüklein konsantrasyonunun 300 pg/mL'den 100 pg/mL'ye düşmesi XIST'nin antienflamatuvar yönünü ortaya koymaktadır. Zenginleştirilmiş gen seti analizleri, XIST susturulmuş grupta farklı şekilde ifade edilen genlerin daha çok nöronal ve bağışıklık ilişkili olduğunu ortaya koymaktadır. Son olarak XIST'nin susturulmasının serebral organoidlerde enflamasyon, miyelinasyon ve nöronal büyüme ve farklılaşmada etkili olması XIST'nin MS patojenezindeki etkisini göstermektedir.
  • Article
    Role of Long Non-Coding RNA X-Inactive Transcript (XIST) in Neuroinflammation and Myelination: Insights From Cerebral Organoids and Implications for Multiple Sclerosis
    (MDPI, 2025) Pepe, Nihan Aktas; Acar, Busra; Zararsiz, Gozde Erturk; Guner, Serife Ayaz; Sen, Alaattin; Erturk Zararsiz, Gozde; Ayaz Guner, Serife; Aktas Pepe, Nihan
    Background/Objectives: X-inactive-specific transcript (XIST) is a factor that plays a role in neuroinflammation. This study investigated the role of XIST in neuronal development, neuroinflammation, myelination, and therapeutic responses within cerebral organoids in the context of Multiple Sclerosis (MS) pathogenesis. Methods: Human cerebral organoids with oligodendrocytes were produced from XIST-silenced H9 cells, and the mature organoids were subsequently treated with either FTY720 or DMF. Gene expression related to inflammation and myelination was subsequently analyzed via qRT-PCR. Immunofluorescence staining was used to assess the expression of proteins related to inflammation, myelination, and neuronal differentiation. Alpha-synuclein protein levels were also checked via ELISA. Finally, transcriptome analysis was conducted on the organoid samples. Results: XIST-silenced organoids presented a 2-fold increase in the expression of neuronal stem cells, excitatory neurons, microglia, and mature oligodendrocyte markers. In addition, XIST silencing increased IL-10 mRNA expression by 2-fold and MBP and PLP1 expression by 2.3- and 0.6-fold, respectively. Although XIST silencing tripled IBA1 protein expression, it did not affect organoid MBP expression. FTY720, but not DMF, distinguished MBP and IBA1 expression in XIST-silenced organoids. Furthermore, XIST silencing reduced the concentration of alpha-synuclein from 300 to 100 pg/mL, confirming its anti-inflammatory role. Transcriptomic and gene enrichment analyses revealed that the differentially expressed genes are involved in neural development and immune processes, suggesting the role of XIST in neuroinflammation. The silencing of XIST modified the expression of genes associated with inflammation, myelination, and neuronal growth in cerebral organoids, indicating a potential involvement in the pathogenesis of MS. Conclusions: XIST may contribute to the MS pathogenesis as well as neuroinflammatory diseases such as and Alzheimer's and Parkinson's diseases and may be a promising therapeutic target.
  • Article
    Citation - WoS: 3
    Citation - Scopus: 4
    Biochemical, Pharmacological, and Toxicological Attributes of Caper (Capparis Ovata) Flowering Buds and Berries Pickles
    (Wiley, 2022-07-30) Ozgun-Acar, Ozden; Celik-Turgut, Gurbet; Guner, Huseyin; Sezer, Serdar; Sen, Alaattin
    Capparis ovata is a natural plant that grows widely in Turkey and its flowering buds and berry pickle are used in traditional medicine. Thus, the current study was expanded to evaluate the biochemical, pharmacological, and toxicological aspects of the Capparis ovata water extract (COWE). To determine the biochemical properties of COWE, mineral and fatty acid content, elemental analysis, flavonoid/phenolic content, radical-scavenging capacity, and pesticide analysis were performed. Furthermore, to find out whether it had anti-inflammatory properties, reverse transcription-polymerase chain reaction (RT-PCR) and nuclear factor kappa B (NF-kappa B) luciferase activity tests were conducted. Whole-genome transcriptomic profiling was carried out at a dose level of 500 mg/kg COWE to understand its pharmacological effect. Transaminases in serum were tested, and quantitative polymerase chain reaction (qPCR) was done using a custom design array that included the stress and molecular toxicology pathway to establish its toxicological qualities. As a result of the evaluations, it was observed that COWE has a high mineral and unsaturated fatty acid content, flavonoid/phenolic content, and radical-scavenging ability. It significantly inhibited NF-kappa B transcriptional activity as well as inflammatory cytokine expression in T-lymphoblast cells. Whole-genome transcriptomic profiling depicted that COWE modulates immune responses by upregulating natural killer cell activation, cellular response to type I interferon, B-cell proliferation and differentiation, and Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathways. Molecular Toxicology Pathfinder RT2 Profiler PCR array analysis revealed that COWE at or lower dose of 500 mg/kg/day did not cause a comparatively adverse effect. According to the findings, COWE is a rich source of nutrients and can be used as an adjunct therapy for various inflammatory diseases.

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