Browsing by Author "Şen, Alaattin"

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Biochemical, pharmacological, and toxicological attributes of caper (Capparis ovata) flowering buds and berries pickles
(WILEY, 2022) Ozgun-Acar, Ozden; Celik-Turgut, Gurbet; Guner, Huseyin; Sezer, Serdar; Sen, Alaattin; 0000-0002-8444-376X; 0000-0002-0220-5224; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Güner, Hüseyin; Şen, 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, radicalscavenging 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-κB) 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-κB transcriptional activity as well as inflammatory cytokine expression in T-lymphoblast cells. Wholegenome 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
Complementary medicines used in ulcerative colitis and unintended interactions with cytochrome P450-dependent drug-metabolizing enzymes
(TUBİTAK, 2022) Şen, Alaattin; 0000-0002-8444-376X; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Şen, 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 drugmetabolizing 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.
Role of AHR, NF-kB and CYP1A1 crosstalk with the X protein of Hepatitis B virus in hepatocellular carcinoma cells
(ELSEVIER, 2023) Celik-Turgut, Gurbet; Olmez, Nazmiye; Koc, Tugba; Ozgun-Acar, Ozden; Semiz, Asli; Dodurga, Yavuz; Satiroglu-Tufan, Naciye Lale; Sen, Alaattin; 0000-0002-8444-376X; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Şen, Alaattin
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 pre-sent 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.