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    Comprehensive study of chemical composition and biological activity of Thymus pubescens Boiss. et Kotschy ex Celak
    (Elsevier, 2022) Yigitkan, Serkan; Akdeniz, Mehmet; Yener, Ismail; Seker, Zeki; Yilmaz, Mustafa Abdullah; Firat, Mehmet; Kavak, Deniz Evrim
    The use of Thymus species amongst the public and their importance in the scientific world is increasing day by day. In addition to being consumed as tea and spice, Thymus species are used as folk medicine for respiratory, digestive, skin, circulatory, genital, nervous, visual and urinary diseases. In this study, it was aimed to examine the essential oil and ethanol extract of the root and aerial parts of Thymus pubescens Boiss. et Kotschy ex Celak in the terms of their biological activity and chemical content. The phenolic content of the species was determined by LC-MS/MS, while triterpenoid content, the chemical composition of the essential oil as well as flavour was determined by GC-MS. In addition, their antioxidant and cytotoxic activities, as well as acetyl- (AChE) and butyrylcholinesterase (BChE), urease, tyrosinase, elastase, collagenase, HMG-CoA reductase and angiotensin-converting enzyme (ACE) inhibitory activities were studied. Thymol (53.33%) was determined as the major component in the essential oil, while b-fenchyl alcohol (43.87%) was determined as the major component of the flavour. According to the LC-MS/MS and GC-MS results, it was found that especially the aerial parts of the species have a high amount of rosmarinic acid (3875.76 mg analyte/g extract), quinic acid (2392.55), naringenin (970.39), oleanolic (92785.96) and ursolic (63373.32) acids. The essential oil of T. pubescens species was observed to show high activity in four antioxidant assays, e.g. inhibition of lipid peroxidation, DPPH and ABTS radical scavenging activity as well as CUPRAC, while the ethanol extracts showed moderate antioxidant activity. In enzyme inhibition assays, the aerial parts exerted marked BChE, elastase, and collagenase inhibitory activities (92.43 +/- 1.28%, 42.59 +/- 0.56, and 48.61 +/- 0.39 at 100 mg/mL, respectively). On the other hand, AChE, urease, tyrosinase, HMG-CoA reductase and ACE inhibitory activities of all extracts were from low to moderate levels. In particular, the aerial parts of the species displayed a high cytotoxic effect (vitality%: 6.82 +/- 0.01 at 200 mg/mL) in breast cancer (MCF-7) cell line. Due to its remarkable antioxidant capacity, high content of rosmarinic, oleanolic, and ursolic acids and especially BChE, elastase, and collagenase inhibitory activity, T. pubescens has the potential for using in food supplements, food preservatives, cosmetics, and pharmaceutical industries.(c) 2022 SAAB. Published by Elsevier B.V. All rights reserved.
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    Ecofriendly synthesis of silver nanoparticles using ananas comosus fruit peels: Anticancer and antimicrobial activities
    (Hindawi LTD, 2022) Baran, Ayşe; Keskin, Cumali; Baran, Mehmet Fırat; Huseynova, Irada; Khalilov, Rovshan; Eftekhari, Aziz; Kandemir, Sevgi İrtegün; Kavak, Deniz Evrim
    Metallic nanoparticles are valuable materials and have a range of uses. Nanoparticles synthesized from plant wastes by environment-friendly methods have attracted the attention of researchers in recent years. Also, the advantages of biological resources and synthesis methods are attracting attention. In this study, silver nanoparticles were synthesized from Ananas comosus fruit peels using ecofriendly method steps. The characterization of the particles obtained was determined by using a UV-visible spectrophotometer (UV-Vis.), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction diffractometer (XRD), Fourier scanning electron microscope (FESEM), and transmission electron microscopy (TEM). The nanoparticles showed maximum absorbance at 463 nm, measuring 11.61 in crystal nanosize, and presented spherical in appearance. An antimicrobial activity test was determined with the minimum inhibition concentration (MIC) method. The nanoparticles showed promising inhibitory activity on the Gram-positive and Gram-negative pathogen microorganisms (Escherichia coli ATCC25922, Staphylococcus aureus ATCC29213, Bacillus subtilis ATCC11774, Pseudomonas aeruginosa ATCC27833 bacteria, and Candida albicans yeast) at low concentrations. The cytotoxic and growth inhibitory effects of silver nanoparticles on different cancer cell lines were examined via the MTT assay.
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    The M1/M2 Macrophage Polarization and Hepatoprotective Activity of Quercetin in Cyclophosphamide-Induced Experimental Liver Toxicity
    (Wiley, 2025) Seker, Ugur; Uyar, Emre; Gokdemir, Gul Sahika; Kavak, Deniz Evrim; Irtegun-Kandemir, Sevgi
    Background: Chemotherapy drugs may lead to hepatic injury, which is considered one of the limitations of these drugs. Objectives: The aim of this study was to evaluate the effect of quercetin (QUE) on M1/M2 macrophage polarization and hepatoprotective effect in cyclophosphamide (CTX)-induced liver toxicity. Methods: Twenty-four mice were divided into four groups (Control, QUE, CTX, CTX + QUE). The CTX and CTX + QUE groups received 200 mg/kg CTX. The animals in the QUE and CTX + QUE groups received 50 mg/kg QUE. All animals were sacrificed, and serum and liver samples were used for laboratory analyses. Results: Examinations indicated that CTX exposure led to disruption of liver functions and morphological degenerations. Tissue pro-apoptotic Bax and caspase 3, pro-inflammatory TNF-alpha and IL-1 beta, transcription factor NF-kappa B, and M1 macrophage polarization marker CD86 were upregulated significant (p < 0.05) in this group. In addition, CTX exposure led to significantly (p < 0.05) upregulation of the Bax/Bcl-2 mRNA ratio and DNA fragmentations. The PCNA-positive hepatic cell ratio and anti-apoptotic Bcl-2 expression are remarkably suppressed (p < 0.05). Immunohistochemical analyses are also indicated that M2 macrophage polarization marker CD163 is slightly but remarkably (p < 0.05) downregulated in the CTX group compared to the Control and QUE groups. The morphological and biochemical disruptions were alleviated in QUE-treated animals in the CTX + QUE group. Liver function test results, apoptosis, inflammatory, transcription factor NF-kappa B, regeneration/proliferation, and apoptotic index results in this group were similar (p > 0.05) to the control and QUE groups. The M1 cell surface marker expression of CD86 is significantly (p < 0.05) downregulated, and M2 macrophage polarization marker expression of CD163 is upregulated significantly (p < 0.05) compared to the CTX group. Conclusions: This study indicates that QUE has the potential to downregulate CTX-induced hepatic injury and regulate M1/M2 macrophage polarization to the M2 side, which indirectly demonstrates activation of anti-inflammatory signalling and tissue repair.
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    Mitochondrial miRNAs and fibromyalgia: new biomarker candidates
    (Springer Science and Business Media B.V., 2025) Kavak, Deniz Evrim; Dilek, Banu; Rasulova, Khayala; Pehlivan, Melek; Kızıldağ, Sefa
    ntroduction / objective: Fibromyalgia syndrome (FMS), affecting 3–10% of the population, presents a challenge due to its complex symptomatology. Mitochondrial miRNAs (mitomiRs) are highlighted for their significant role in metabolic disorders. This study aimed to assess demographic data in Primer FMS patients and explore potential targets through mitomiR profiling. Methods: In our study, we examined 17 FMS patients and 18 controls, chosen based on specific criteria. Mitochondria were isolated from PBMCs in patient/control blood samples using the MACS method. Mitochondrial purity was verified through RT-qPCR and Western Blot. Following this, we extracted microRNAs and analyzed the levels of 3 mitochondrial miRNAs linked to oxidative stress (mitomiR-145-5p, mitomiR-23a-3p, mitomiR-223-3p) using RT-qPCR. Results: It was found that pain (P < 0.0001), fatigue (P = 0.0005), sleep quality (P < 0.0001), and depression (P < 0.0001) scores were significantly different in the FMS patient group compared to the control group. But the average BMI values have no difference compared to the control group (p = 0.7473). For the first time, a significant increase in mitomiR-145-5p was observed in the PBMCs of FMS patients compared to the control group (p = 0.0010). There was no significant difference observed in the gene expression levels of mitomiR-223-3p (p = 0.1623) and mitomiR-23a-3p (p = 0.4897). Conclusion: We demonstrated that mitomiR-145-5p plays a significant role in the progression of FMS pathology. Our study offers new insights, suggesting that mitochondrial miRNAs may have roles in FMS patients, which has not been previously investigated in the literature, thus providing a fresh perspective on the condition.
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    Modis-Aqua uydu verilerinden Beyşehir Gölü'nün 20 yıllık deniz suyu yüzeyi sıcaklığı ve klorofil-a pigment konsantrasyon incelemesi
    (Iksad Publications, 2023) Karadoğan, Sabri; Kavak, M.Tahir; Kavak, Deniz Evrim; Hatipoğlu, Recep; Yağız, Kadir
    Zararlı alg patlamalarının kontrol edilmesinde klorofil-a konsantrasyonunun (khl-a) zamansal dağılımının anlaşılması kritik bir role sahiptir. Bu çalışma, Modis-Aqua'nın elde ettiği verileri kullanarak yakın tarihte alg patlaması görülen Beyşehir Gölü'nün uzun süreli deniz suyu yüzey sıcaklığı (SST) ve klorofil-a pigment konsantrasyonunun incelemesine yoğunlaşmıştır. Uzun süreli SST değişkenliği ve bu değişkenliğin fitoplankton biyokütlesini temsil eden khl-a pigmenti ile ilişkisi Orta Çözünürlüklü Görüntüleme Spektroradiometresi (MODIS-Aqua) uydu verileri kullanılarak araştırıldı. MODIS 2002' den 2022' ye aylık değişkenlik khl-a ve SST’ de araştırıldı ve SST ile khl-a arasında P<0.0001 anlamlı korelasyon bulundu. Uzun süreli araştırılan khl-a verileri 11 Ekim 2013’ te 36.652 mg/m3 ve 7 Eylül 2021’ de 96.456 mg/m3 olarak maksimum değer göstermiş olup, 7 Eylül 2021’ deki artış gazetelerde yayınlanan Beyşehir Gölü yeşile boyandı haberiyle örtüşmüştür. Ek olarak, Beyşehir Gölü'nün lineer trend çizgisi; SST ve khl-a değerlerinde zamanla artma eğiliminde olduğu gözlemlenmiştir. Bu eğilimin nedeni Beyşehir Gölü ve çevresinin küresel iklim değişikliğine bağlı faktörlerin etkilerinin yanı sıra su seviye değişimleri ve çevre koşulları ile ilgili ciddi sorunlar yaşaması olarak öngörülmektedir. Sonuç olarak deniz suyu yüzeyi sıcaklığı ve klorofil-a her zaman alg patlamaları için en önemli kontrol faktörleri arasındadır. Önerilen veriler, Beyşehir gölündeki alg patlamalarının önlenmesi için bir erken uyarı sistemi geliştirilmesinde potansiyel olarak kullanılabilir.
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    The nephroprotective effect of Quercetin in Cyclophosphamide-induced renal toxicity might be associated with MAPK/ERK and NF-κB signal modulation activity
    (Taylor and Francis Ltd., 2024) Şeker, Uğur; Kavak, Deniz Evrim; Dokumacı, Fatma Zehra; Kızıldağ, Sefa; Kandemir, Sevgi İrtegün
    The present study aimed to examine the protective effect of quercetin (QUE) on cyclophosphamide (CTX)-induced nephrotoxicity. For that purpose, 24 mice were divided into four groups (Control, QUE, CTX, and CTX + QUE). The CTX and CTX + QUE groups received 200 mg/kg of cyclophosphamide on the 1st and 7th days. The QUE and CTX + QUE groups were treated with 50 mg/kg of quercetin daily for 14 days. At the end of the experiment, the animals were sacrificed, and kidney samples were analyzed. The results indicated that CTX leads to severe morphological degenerations and disruption in renal function. Serum BUN, Creatinine, Uric acid, tissue Bax, Caspase 3, TNF-α and IL-1β expression levels were upregulated in the CTX group compared to Control and QUE groups (p < 0.05). Although MAPK/ERK phosphorylation level is not affected in CTX group, there was a significant increase in CTX + QUE group (p < 0.05), but the NF-κB was significantly suppressed in this group (p < 0.01). The RT-qPCR results showed that the cyt-c and the Bax/Bcl-2 ratio mRNA expression folds were upregulated in the CTX group (p < 0.01), which was downregulated in the CTX + QUE group. However, there was a significant difference in the CTX + QUE group compared to the Control and QUE groups (p < 0.01). The findings showed that administering quercetin along with cyclophosphamide alleviated renal injury by regulating apoptotic and inflammatory expression. Moreover, the administration of quercetin and cyclophosphamide could synergistically improve renal function test results, and activate cellular responses, which upmodulate MAPK/ERK phosphorylation and suppression of NF-κB.
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    Targeting soluble guanylate cyclase with Riociguat has potency to alleviate testicular ischaemia reperfusion injury via regulating various cellular pathways
    (John Wiley and Sons Inc, 2022) Şeker, Uğur; Kavak, Deniz Evrim; Güzel, Barış Can; Baygeldi, Saime Betül; Yüksel, Meral; Kandemir, Sevgi İrtegün; Şener, Dila; Demirel, Özlem Unay
    Testicular ischaemia reperfusion (I/R) injury results with serious dysfunctions in testis. This study aims to explore effects of soluble guanylate cyclase (sGC) stimulator Riociguat on experimental testicular I/R injury in rats. Twenty-one male rats were divided into three groups (Control, IR and IRR). The control group was not exposed to any application. Bilateral testis from IR and IRR animals were rotated 720° in opposite directions for 3 h to induce experimental testicular ischaemia. Animals in IR and IRR groups were subjected to 3 h of reperfusion. Isotonic and Riociguat were administered to the animals 30 min prior reperfusion by oral gavage. At the end of experiment, animals were sacrificed and tissue samples were used for analyses. Riociguat treatment significantly decreased tissue malondialdehyde and Luminol levels compared to the IR group (p < 0.05). The pathological changes, pro-apoptotic proteins (Bax, Caspase 3, and Caspase 9) and apoptotic index in the IR group were down regulated in Riociguat treated animals (p < 0.05). Riociguat treatment was also significantly increased anti-apoptotic Bcl-2 expression, but alleviated tissue injury via modulating pro-inflammatory cytokine IL-1β levels and significantly (p < 0.05) down-regulating NF-κB activity. Moreover, mTOR and ERK phosphorylation increased in IR group (p < 0.05), but Riociguat treatment reduced protein phosphorylation. Our experiment indicated that targeting sGC might support surgical interventions in testicular I/R injury by modulating oxidative stress, inflammation, and apoptotic protein expression levels, but more detailed studies are required to explore the protective activity of Riociguat and underlying mechanisms in testicular I/R injury.