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    Investigation of the effects of safranal on the experimentally created rheumatoid arthritis model in rats
    (Wiley, 2022) Cellat, Mustafa; Isler, Cafer T.; Kutlu, Tuncer; Kuzu, Muslum; Etyemez, Muhammed; Alakus, Halil; Guvenc, Mehmet
    Rheumatoid arthritis (RA) is a systemic chronic disease characterized by inflammation and synovitis. More effective treatment methods with less side effects need to be developed. In this context, current study investigated the therapeutic effects of safranal in a model of complete Freund's adjuvant (CFA)-induced RA. The control group was given 1 ml of saline orally starting from the 8th day, and 0.2 ml of CFA was given to the RA, RA + Safranal and RA + Methotrexate (MTX) groups on the 0th day of the experiment. Starting from the 8th day of the experiment, 1 ml of saline was given to the RA group, safranal was given at 200 mg/kg of body weight to the RA + MTX group, and 3 mg/kg of MTX to the RA + MTX group twice a week. The results showed that weight gain decreased in the RA group compared to the control group while arthritis index score, thymus index, and planter temperature were found to be increased. Additionally, a deterioration in blood parameters, an increase in alanine aminotransferase, aspartate aminotransferase, urea, creatinine, C-reactive protein, and malondialdehyde levels, and a decrease in reduced glutathione levels and glutathione peroxidase and catalase (CAT) activities were seen while tumor necrosis factor-alpha, interleukin-6 (IL-6), cyclooxygenase-2, nuclear factor kappa B levels were found to be increased. However, the safranal had a regulatory effect on all the values, except IL-6 and CAT, and blood parameters. Moreover, histopathological examination revealed that safranal reduced inflammatory cell infiltration and edema.
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    Safranal's therapeutic effects in rat models of polycystic ovary syndrome
    (Springernature, 2024) Cellat, Mustafa; Kuzu, Muslum; Guvenc, Mehmet; Yuksel, Murat; Kanat, Ozgur; Bozkurt, Yesim Akaydin; Etyemez, Muhammed
    Polycystic ovary syndrome is one of the leading causes of female infertility in reproductive age. In this work, the protective effects of safranal against letrozole-induced polycystic ovary syndrome in rats were examined. For this purpose, 32 Wistar albino female rats were split into four groups. Each group received the following treatments for 21 days: Group 1 received carboxymethylcellulose (1%, 2 ml/kg); Group 2, letrozole (1 mg/kg), Group 3, safranal (200 mg/kg); and Group 4 letrozole and safranal via oral gavage. We identified estrus cycles in the rats and analyzed various parameters in their serum and ovarian tissues, as well as histopathologic findings. The parameters studied included C-reactive protein, glucose, total cholesterol, triacylglyceride, high-density lipoprotein, low-density lipoprotein, follicle-stimulating hormone, estradiol, and luteinizing hormone levels in serum. Additionally, the study measured malondialdehyde, glutathione, glutathione peroxidase, and catalase levels in ovarian tissue. We also examined tumor necrosis factor-alpha, interleukin-6, and interleukin-1beta parameters in serum and ovarian tissues, as well as nuclear factor erythroid 2-related factor-2 and heme oxygenase-1 protein levels. In the letrozole group, the estrus cycle was disrupted, and all parameters, except for glutathione and glutathione peroxidase, showed impairments compared to the control group. The findings showed that glucose, triacylglyceride, catalase, and heme oxygenase-1 levels slightly improved after safranal treatment, however, other parameters showed statistically significant improvements. Furthermore, safranal treatment reduced the development of cystic follicles while preserving tissue architecture, as revealed by histopathologic findings. Based on the results obtained, it may be argued that safranal's antioxidant and anti-inflammatory properties, along with its ability to regulate sex hormone levels and manage dyslipidemia, make it a promising solution for patients with polycystic ovary syndrome.
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    Zingerone protects liver and kidney tissues by preventing oxidative stress, inflammation, and apoptosis in methotrexate-treated rats
    (Taylor & Francis Ltd, 2022) Turk, Erdinc; Guvenc, Mehmet; Cellat, Mustafa; Uyar, Ahmet; Kuzu, Muslum; Aggul, Ahmet Gokhan; Kirbas, Akin
    The clinical use of drugs used in the treatment of diseases is limited due to the toxic side effects, and many studies have been conducted to benefit from herbal adjuvant therapies recently to eliminate these effects. In this study, the protective effect of zingerone against liver and kidney damage generated in rats through methotrexate (MTX). Histopathological investigations were performed to determine tissue damage caused by MTX and the healing effect of zingone and liver function markers such as serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and renal function markers such as urea, creatine, and aquaporin-1 (AQP-1) were measured. The effects of MTX and protective properties of zingerone on oxidative stress were investigated through the measurement of malondialdehyde and reduced glutathione (GSH) levels, catalase (CAT), and glutathione peroxidase (GPx) enzyme activities. The anti-inflammatory effect of zingerone was determined by measuring the cytokine levels causing inflammation such as nuclear factor-kappa B (NF-kappa B), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta), and its effects on apoptosis were determined by immunohistochemical analysis of caspase-3 and B-cell lymphoma-2 (Bcl-2) expression levels. According to the results obtained within the scope of the study, it was determined that zingerone treatment prevented the increase in MTX-induced liver and kidney function markers, showed healing effects on antioxidant parameters degraded in both tissues, and decreased the inflammation parameters. It was determined that it also prevented apoptosis and possessed a protective effect on disrupted tissue architecture by decreasing the increased caspase-3 expression and increasing the decreased Bcl-2 level.