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Öğe Dermal absorption and toxicity of alpha amanitin in mice(Informa Healthcare, 2014) Kaya, Ertugrul; Surmen, Mustafa Gani; Yaykasli, Kursat Oguz; Karahan, Selim; Oktay, Murat; Turan, Hakan; Colakoglu, SerdarThe fungus Amanita phalloides is known to contain two main groups of toxins: amanitins and phallotoxins. The amanitins group effectively blocks the RNA polymerase II enzyme found in eukaryotic cells. As alpha amanitin has a lethal effect on the majority of eukaryotic cells, it can be valuable as an antiparasitic or antifungal drug. It can be used externally against ectoparasites. It is critical that percutaneous applications of the alpha amanitin toxin are not harmful to the recipient. In this study, the absorption and the toxicity of percutaneous and intraperitoneal (ip) applications of 1 mg/kg alpha amanitin to mice were compared. Potential skin, liver and kidney toxicities were investigated through pathological examination. HPLC analysis was used to determine the amount of the toxin. No toxicity or toxin were found in the skin, liver, or kidneys of the mice in the control group. Interestingly, the percutaneous application group also showed no toxicity, and the toxin was not present in this group. After 24 h, Councilman-like bodies and pyknotic cells were observed in the mice in which alpha amanitin was applied intraperitoneally, demonstrating the presence of toxicity. Peak levels of alpha amanitin (mu g/mL) in the liver, kidney, and blood in the ip application group were measured at 3.3 (6 h), 0.2 (6 h) and 1.2 (1 h), respectively. The results demonstrated that the toxin was not absorbed through the skin of the mice and that the percutaneous application of alpha amanitin did not have any toxic effects. Thus, alpha amanitin may be administered percutaneously for therapeutic purposes.Öğe Efavirenz'in anksiyojenik ve depresyon benzeri etkilerinde monoaminerjik, gabaerjik ve nitrerjik sinir iletim sistemlerinin rolü(Dicle Üniversitesi, Sağlık Bilimleri Enstitüsü, 2019) Karahan, Selim; Erdinç, MeralAmaç: Efavirenz (EFV), HIV-1 tedavisinde sıklıkla kullanılan bir ilaçtır. EFV ile tedavinin ilk haftalarında birçok nöropsikiyatrik yan etkinin gelişimesi, kullanımını kısıtlayan bir durumdur. Bu çalışmada, akut EFV uygulamasının farelerde anksiyete ve depresyon benzeri nöropsikiyatrik yan etkileri ve bu etkilere aracılık eden nöronal mekanizmaları ortaya koymak amacıyla EFV'in prefrontal korteks (pFK) dokularında mitokondriyal ve nöronal fonksiyonlar, oksidatif stres ve inflamasyon mekanizmaları üzerine olan etkileri araştırıldı. Gereç ve Yöntem: Çalışmamızda, BALB/c türü erkek fareler Kontrol, EFV, EFV+ATR, EFV+BCL, EFV+ M10907, EFV+SHTN, EFV+HPDL, EFV+FBZM, EFV+PRPL ve EFV+AMGN olarak 10 gruba (n=7) ayrıldı. Herbir grupta, deneklere EFV (20 mg/kg, i.p.) uygulamasından 30 dk. önce monoaminerjik, GABAerjik ve nitrerjik reseptör antagonistleri (i.p.) uygulandı. İlaç uygulamalarından 60 dk. sonra denekler açık alan, yükseltilmiş artı labirent, aydınlık/karanlık kutusu, kuyruktan asma ve zorunlu yüzme testlerine tabi tutularak psikofarmakolojik incelemeler gerçekleştirildi. Sakrifiye edilen farelerin pFK dokularında BDNF, VEGF-A, PGC-1?, TFAM, UCP-2, IL-1?, IL-6 ve TNF-? genlerinin ekspresyon düzeyleri Real-time PZR yöntemi ile ölçüldü. pFK dokularında malondialdehit düzeyleri ölçülerek biyokimyasal incelemeler gerçekleştirildi. Bulgular: Akut EFV uygulaması, farelerde anksiyete ve depresyon benzeri davranış değişikliklerine neden oldu. Gelişen depresyon ve anksiyete tablosu, atropin ve aminoguanidin ile tersine çevrildi. EFV, pFK dokularında BDNF ve TFAM genlerinin ekspresyonlarını önemli şekilde düşürdü; IL-1? düzeylerini arttırdı. Düşmüş olan BDNF düzeyleri M10907 ile tersine çevrildi. Artan IL-1? düzeylerinin ise siproheptadin ve aminoguanidin ile tersine çevrildiği görüldü. EFV'in, pFK dokularında malondialdehit seviyelerini arttırdığı saptandı. Sonuç: Çalışmamızda, EFV'in anksiyojenik ve depresyon benzeri etkilerinde nitrerjik ve kolinerjik sinir iletim sistemlerinin önemli rollerinin bulunduğu, EFV uygulamasının nöronal fonksiyonları ve mitokondriyal enerji homeostazını bozduğu, inflamatuar ve oksidatif stres ile ilgili mekanizmaları tetiklediği görülmüştür.Öğe Effect of Pleurotus ostreatus Water Extract Consumption on Blood Parameters and Cytokine Values in Healthy Volunteers(Routledge Journals, Taylor & Francis Ltd, 2024) Dundar, Abdurrahman; Yalcin, Pinar; Arslan, Nurgul; Acay, Hilal; Hatipoglu, Abdulkerim; Boga, Mehmet; Karahan, SelimObjective: Our aim in this study is, does 29-day regular consumption of Pleurotus ostreatus water extract by volunteer individuals who meet the study criteria have an effect on blood and cytokine values? Method: In accordance with the purpose of the study, volunteers were asked to consume 100 ml of the extract every morning for 29 days. Three tubes of blood samples were taken from the volunteers on the 15th and 29th days of the study. Biochemical and hematological analysis of the blood samples were performed and immunomodulatory effects through cytokines were examined. The values obtained from 3 tubes of blood obtained from volunteers before the use of mushroom extract were used as control. The chemical composition and beta-glucan content of 100 ml of mushroom water extract were also analyzed. Result: IL-4, IL-6, IL-10 and IL-13 could not be detected because the values were below the lowest standard value. TNF-alpha, IFN-gamma and IL-1 beta 15th and 29th day values decreased compared to the 1st day (control) values (p < 0.05). However, there was no significant difference observed between the 15th and 29th day. No abnormalities were observed in biochemical and hematological values. Also, the beta-glucan content of extract was found 38.12 mg/100 ml. Conclusion: The frequency range of kidney and liver function test results confirmed that P. osreatus is a reliable food source. Considering the cytokine values these results indicate that P. ostreatus water extract has an anti-inflammatory effect. As no significant difference was observed in 29 days of use, it is thought that 15 days of daily consumption of the extract may be sufficient for the anti-inflammatory effect to occur. However, a large number of qualified clinical trials are needed to support the issue.Öğe Evaluation of the medicinal potential of a traditionally important plant from Turkey: Cerinthe minor L.(Istanbul University Press, 2022) Ersoy, Ezgi; Karahan, Selim; Boğa, Mehmet; Çınar, Ercan; İzgi, Sevcan; Kara, Emel MataracıBackground and Aims: Cerinthe minor L. has been used for both culinary and medicinal purposes in Turkey. Since the plant has remained uninvestigated pharmacognostically, this study aims to provide data on the phytochemical profile and in vitro biological activities of the ethanol extract prepared from the aerial and root parts of Cerinthe minor L. Methods: The phytochemical profile of the extract was determined by LC-MS/MS. Total phenolic and total flavonoid contents of Cerinthe minor ethanol extract were determined as pyrocatechol, and quercetin equivalents, respectively. Antioxidant activity of the extract was investigated by DPPH, and ABTS cation radical scavenging activity, and CUPRAC activity assays. Enzyme inhibitory activity assays were used to investigate anticholinesterase, antityrosinase, and antiurease activities. Cytotoxic potential of the plant was clarified by using the XTT method, and antimicrobial activity of the extract was established by the microbroth dilution technique. Results: According to the LC-MS/MS results, 11 different constituents were present in the extract, and the major com-pounds were, malic acid (5392.18 +/- 60.93 mu g/g extract), fumaric acid (4730.99 +/- 58.66 mu g/g extract), and rosmarinic acid (2470.07 +/- 176.12 mu g/g extract). Total phenolic and flavonoid contents were found as 10.39 +/- 0.73 mu g PEs/mg extract, and 0.75 +/- 0.07 mu g QEs/mg extract, respectively. The extract demonstrated moderate antioxidant activity, whereas no enzyme inhibitory activity was exerted against the tested enzymes. No cytotoxic activity was observed on human renal (A498, UO-31) or human colon (COLO205, KM12) cancer cell lines. The extract was shown to possess low-moderate antimicrobial activity against C. tropicalis with a MIC value of 78.12 mu g/mL. Conclusion: Having several pharmacologically valuable compounds, and not causing any toxicity on studied cell lines, Cerin-the minor is a plant that requires attention with its medicinal potentialÖğe Gene expression profiles for apoptotic and necrotic pathways during Amanita phalloides intoxication in mice(Istanbul Univ, Fac Pharmacy, 2022) Karahan, Selim; Atli, Zehra; Kaya, Ertugrul; Ozdemir, Feride; Boga, Mehmet; Izgi, SevcanBackground and Aims: Amanita phalloides is the deadliest toxic mushroom in the world and causes death from acute liver failure. alpha-amanitin (alpha-AMA), the most potent toxin, inhibits RNA polymerase II in hepatocytes, stops protein synthesis, and causes hepatotoxicity. However, the information about the mechanisms underlying hepatotoxicity caused by alpha-AMA is quite inadequate. This study aims to reveal the complex necrotic and apoptotic mechanisms occurring in mouse hepatocytes de-pending on A. phalloides exposure time in vivo.Methods: BALB-c male mice were divided into 5 groups (n=7): control, alpha-AMA-2, alpha-AMA-12, alpha-AMA-72, and alpha-AMA-96 groups. A poisoning model was created by oral administration of A. phalloides mushroom extract containing 10 mg/kg of alpha-AMA to mice and they were sacrificed after 2, 12, 72, and 96 h. Then, TNF-alpha, Bax, caspase-3, and Bcl-2 gene expression levels in liver tissues were examined by the RT-qPCR method. Time-dependent damage to liver tissues was also evaluated histopathologically.Results: RT-qPCR results showed that proinflammatory cytokine TNF-alpha mRNA expression levels increased in mouse liver tissues at 2 and 12 h afterA. phalloides administration compared among the groups. BaxmRNA expression levels increased in the 12 and 72 h afterA. phalloides ingestion. It was observed that caspase-3 mRNA expression levels increased in the 72 and 96 h groups compared among the groups, while Bcl-2 mRNA expression levels decreased in the 72 and 96 h groups.Conclusion: Our findings showed that necrotic mechanisms develop in the early period afterA. phalloides mushroom poison-ing, and then apoptotic mechanisms are effective. In conclusion, understanding the mechanisms of A. phalloides-induced hepatotoxicity will provide important information for new treatment strategies to be developed.Öğe Lidokainin streptozotosin ile indüklenen alzheimer hastalığının deneysel modeli üzerindeki etkisi(Türk Nöropsikiyatri Derneği, 2023) Tamam, Yusuf; Yokuş, Beran; Tamam, Cüneyt; Yüceer, Hande; Karahan, Selim; Em, Bernan; Tamam, Şerife Banu; Tüzün, ErdemAmaç: Alzheimer hastalığı (AH), serebral korteks ve hipokampusta amiloid plakların birikmesinden kaynaklanan nörodejeneratif bir hastalıktır. Bu çalışmada, streptozotosin (STZ) ile indüklenen sıçan AH modelinde lokal anestezik lidokainin nörodejenerasyon belirteçleri ve bellek üzerindeki etkileri ilk kez araştırıldı. Yöntem: AH modeli geliştirmek için Wistar sıçanlarına intraserebroventriküler (ICV) olarak STZ uygulandı. Lidokain grubuna (n=14) STZ enjeksiyonuna ek olarak lidokain (5 mg/kg) intraperitoneal (İP) uygulandı. Kontrol grubu hayvanları (n=9) 21 gün boyunca tuzlu su ile tedavi edildi. Enjeksiyonlar tamamlandıktan sonra hafızayı değerlendirmek için Morris Su Labirenti (MWM) testi yapıldı. Ayrıca TAR DNA-binding protein-43 (TDP-43), amyloid precursor protein (APP), β-sekretaz 1, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), response element binding protein (CREB), c-FOS serum seviyeleri ELISA testi ile ölçüldü ve gruplar arasında karşılaştırıldı. Bulgular: Lidokain grubu hayvanlar, MWM’de kadran puanlarında daha düşük kaçış gecikmesi ve süresi gösterdi ve bu da daha iyi bellek performansı çıkardı. Ayrıca lidokain uygulaması TDP-43 düzeylerinde önemli bir düşüşe neden oldu. Ancak APP ve β-sekretaz ekspresyonu AH ve lidokain gruplarında kontrol grubuna göre anlamlı derecede yüksekti. Ayrıca lidokain grubu, AH grubuna göre belirgin şekilde daha yüksek serum NGF, BDNF, CREB ve c-FOS seviyelerine sahipti. Sonuç: Lidokain, STZ ile indüklenen AH modelinde hafızayı iyileştiriyor ve nöroprotektif bir etkiye sahip görünüyor. Bu etki, birkaç büyüme faktörü ve bunlarla ilişkili hücre içi moleküllerin artan seviyeleri ile ilişkili olabilir. Alzheimer hastalığı patofizyolojisinde lidokainin terapötik rolü gelecekte araştırılmalıdır.Öğe Phytochemical analysis of essential oils and the extracts of an ethnomedicinal plant, Teucrium multicaule collected from two different locations with focus on their important biological activities(Elsevier, 2023) Ersoy, Ezgi; Tanaman, Irmak; Özkan, Esra Eroğlu; Karahan, Selim; Şahin, Hasan; Çınar, Ercan; Cantürk, Yeter Yeşil; Kara, Emel Mataracı; Zengin, Gökhan; Boğa, MehmetTeucrium species have been among the most commonly used traditional medicinal plants and they are known to have extensive therapeutic applications. The main focus of this study, Teucrium multicaule is also renowned for being an important medicinal and aromatic plant in Turkiye. Volatile profiling of the essential oils was conducted by GC MS, phytochemical profiling of the ethanol extracts was carried out by LC HRMS, antioxidant, anticholinesterase, antityrosinase, antiurease, antidiabetic, anticancer, and antimicrobial activities were revealed by different assays. Germacrene D was the most abundant compound in the essential oils from Diyarbakir (TmuD) with 45.4%, and Batman (TmuB) with 54.7%. All extracts were found to be quite rich in phytochemicals by LC HRMS, and herniarin, caffeic acid, naringenin, luteolin, scutellarein, hispidulin, rhamnocitrin, penduletin, eupatilin, (-)-epigallocatechin gallate, hederagenin, and verbascoside were found to be present in all extracts. T. multicaule roots extract from Diyarbakir (TmuRD) demonstrated the highest radical scavenging, a-amylase inhibitory (59.82§0.36%), and antibutyrylcholinesterase activity (61.96§ 1.72%), whereas T. multicaule aerial parts extract from Batman (TmuHB) exhibited the strongest antityrosinase (66.17§0.92%), antiurease (67.85§0.69%), and cytotoxic (54.76 § 1.57 mg/mL) activities. TmuRD also showed significant antimicrobial activity against S. epidermidis with 156.2 mg/mL MIC value. As revealed by this first detailed report on T. multicaule, the plant demonstrates various important biological activities attributed to its rich phytochemicals, which also justifies its use in ethnomedicine.Öğe The Therapeutic potential of ethnomedicinally important Anatolian thyme species: A Phytochemical and biological assessment(Frontiers, 09.06.2022) Özkan, Esra Eroğlu; Ersoy, Ezgi; Cantürk, Yeter Yeşil; Kara, Emel Mataracı; Çınar, Ercan; Şahin, Hasan; Karahan, Selim; Sancaktepe, Kübra Karaca; Yılmaz, Mustafa Abdullah; Boğa, MehmetThyme has been used for various therapeutic purposes in many different cultures, which makes it one of the most riveting medicinal plants throughout history. From its beneficial effects on the respiratory tract or the gastrointestinal system, to its unique skin-related activities, the investigation of the medicinal properties of thyme has always been an alluring topic for researchers aiming to develop conventional medications from this traditional herb. With an incentive to contribute to the extensive thyme research, three Thymus L. species namely Thymus cariensis Hub-Mor. & Jalas (endemic), Thymus praceox subsp. grossheimii (Ronniger) Jalas, and Thymus pubescens Boiss. et Kotschy ex Celak from Turkey were deeply investigated within this study. The analysis of the phytochemical constituents of the extracts was conducted by LC-MS/MS. 12 biologically important secondary metabolites (p-coumaric acid, caffeic acid, salicylic acid, quinic acid, fumaric acid, vanillin, malic acid, rutin, apigenin, naringenin, and nicotiflorin) were detected in all extracts. Their total phenolic and flavonoid contents were calculated (11.15 ± 0.17—61.12 ± 2.59 μg PEs/mg extract, 2.53 ± 0.04—40.28 ± 0.92 μg QEs/mg extract, respectively), and the antioxidant potential of the extracts was evaluated by DPPH and ABTS radical scavenging and CUPRAC activity methods, accordingly, the extracts were shown to possess significant antioxidant activity. Among them, Thymus cariensis Hub-Mor. & Jalas was the most active with IC50 values of 34.97 ± 1.00 μg/ml and 9.98 ± 0.04 μg/ml regarding the DPPH and ABTS radical scavenging assays, respectively, and an A0.5 value of 5.80 ± 0.02 μg/ml according to CUPRAC activity method. Their anticholinesterase, antityrosinase, and antiurease activities were also tested, Thymus cariensis Hub-Mor. & Jalas (35.61 ± 1.20%) and Thymus pubescens Boiss. et Kotschy ex Celak aerial part extract (33.49 ± 1.39%) exhibited moderate antibutyrylcholinesterase activity at 200 μg/ml concentration. The results of the cell viability assay indicated that the extracts demonstrated moderate-to-low cytotoxicity on A498 human renal cell lines. Furthermore, all studied extracts exerted noteworthy antimicrobial activity, especially against Candida tropicalis (MIC values: 19.53—78.12 μg/ml). The presented data substantiates the use of thyme extracts as therapeutic agents in both ethnomedicine and conventional therapies.Öğe Towards a better understanding of commonly used medicinal plants from Turkiye: Detailed phytochemical screening and biological activity studies of two Teucrium L. species with in vitro and in silico approach(Elsevier Ireland Ltd., 2023) Ersoy, Ezgi; Süvari, Goncagül; Ercan, Selami; Özkan, Esra Eroğlu; Karahan, Selim; Tuncay, Evin Aygün; Boğa, MehmetEthnopharmacological relevance: Since ancient times, Teucrium L. species have been among the most commonly used traditional medicinal plants mainly in the Mediterranean region. From tackling gastrointestinal problems to maintaining the healthy functioning of endocrine glands, and from treating malaria to severe dermatological disorders, Teucrium species are known to have extensive therapeutic applications. Teucrium polium L. and Teucrium parviflorum Schreb. are the two members of the genus that have been used in Turkish folk medicine for various medicinal purposes. Aim of the study: To determine the phytochemical compositions of the essential oils and ethanol extracts of Teucrium polium and Teucrium parviflorum collected from different locations in Turkiye along with the investigation of in vitro antioxidant, anticancer, antimicrobial activities, and both in vitro and in silico enzyme inhibitory activities of the extracts. Materials and methods: Ethanol extracts of Teucrium polium aerial parts and roots, and aerial parts of Teucrium parviflorum were prepared. Volatile profiling of the essential oils by GC-MS, phytochemical profiling of the ethanol extracts by LC-HRMS, antioxidant activity by DPPH radical scavenging, ABTS cation radical scavenging, CUPRAC, and metal chelating activity assays, anticholinesterase, antityrosinase, antiurease, activities by different enzyme inhibitory activity assays, anticancer activity by SRB cell viability assay, and antimicrobial activity against a standard panel of bacteria and fungi by the microbroth dilution technique. Molecular docking studies were performed by Autodock Vina (Ver. 1.1.2). Results: The studied extracts were found to be quite rich in various biologically important volatile and phenolic compounds. (−)-Epigallocatechin gallate, which is a molecule renowned for having great therapeutic potential, was the major compound of all extracts. Teucrium polium aerial parts extract was revealed as a great source for naringenin with 16327 ± 685.23 μg/g extract. All extracts exerted significant antioxidant activity by different methods. All extracts demonstrated antibutrylcholinesterase, antityrosinase, and antiurease activities by in vitro and in silico assays. Teucrium polium roots extract stood out with remarkable tyrosinase and urease inhibitory and cytotoxic activities. Conclusion: The obtained results from this multi-disciplinary study proves that the traditional use of these two Teucrium species is justified, and the mechanisms behind are enlightened.Öğe Yüksek Saflıkta Beta Amanitin Üretimi(2012) Yaykaşlı, Kürşat Oğuz; Sarıtaş, Ayhan; Bayram, Recep; Kaya, Ertuğrul; Karahan, Selim; Yaykaşlı, EmineAmaç: Beta amanitin nadiren bilimsel araştırmalarda kullanılmakta ve kullanımı gün geçtikçe artmaktadır. Piyasada bu ürün %90 saflıkta ticari olarak satılmaktadır. Bu araştırmada yüksek saflıkta beta amanitin üretme yöntemi tanımlanmıştır. Yöntem: Saflaştırma işlemi Amanita phalloides mantarlarından ekstraksiyonla yapılmıştır. Öncelikle bu mantarlar toplanmış, ekstrakte edilmiş, 2 defa preparatif HPLC ile saflaştırma işlemi uygulanmıştır. Toksinin karşılaştırması, analitik HPLC sisteminde tutulma zamanı ve ultraviyole spektrumu karşılaştırılması yöntemleriyle yapılmıştır. Bulgular: İlk saflaştırma sonucunda elde edilen beta amanitin saflık oranı %91(±2,36) olarak ölçülmüştür. İkinci saflaştırma sonucunda elde edilen beta amanitin saflık oranı %99,2(±0,38) olarak ölçülmüştür. Saflaştırma sonucu elde ettiğimiz toksin ile beta amanitin standardın UV spektrumlarında her ikisinde de 303 nmde maksimum, 263 nmde minimum absorbans verdiği ve spektrum yapısının aynı olduğu görülmüştür. Sonuç: Tanımladığımız bu yöntemle, >%99 saflıkta beta amanitinin üretilmesi mümkündür.