Sürdürülebilir Kalkınma Amaçları
Yayınlar
- MakaleAçık Erişim2026Scopus SJRQ1Effects of Melatonin Formulations on Caffeine-Evoked Cortical Activity and Pentobarbital-Induced Sleep in Mice
Sahin, Nurhan; Yabas, Mehmet; Er, Besir; Erten, Fusun; Kursun, Oznur Ece Durmaz; Cikim, Ismail Gurkan; Kaplan, Berkan; Erek, Gozde; Ozmen, Busra; Orhan, Cemal
Melatonin has chronobiotic, antioxidant, anti-inflammatory, and neuromodulatory properties, and its oral effects may vary according to formulation. This study compared conventional melatonin with a lipid-multiparticulate (LMP) formulation in two acute pharmacological mouse paradigms. Eighty-four male BALB/c mice were assigned to caffeine-evoked cortical activity or pentobarbital-induced sedative-hypnotic experiments. Mice received caffeine (7.5 mg/kg, i.p.) alone or with standard or LMP-melatonin (10 or 20 mg/kg, oral). ECoG recorded cortical electrical activity under urethane anaesthesia. In a separate cohort, latency to and duration of pentobarbital-induced loss of the righting reflex were measured. Circulating neurochemical and redox markers, as well as neurotransmitter- and inflammation-related gene and protein expression, were evaluated. Caffeine increased spike frequency and altered ECoG amplitude, together with unfavorable changes in circulating neurochemical and redox markers and in neurotransmitter receptor- and inflammation-related outcomes. Both melatonin formulations attenuated several of these changes in a dose-dependent manner, with the strongest effects generally observed in the high-dose LMP-melatonin group. Compared with conventional melatonin, LMP-melatonin produced greater modulation of ECoG activity, circulating biochemical markers, neurotransmitter-receptor expression, and IL-6 and TNF-α-related outcomes. LMP-melatonin also produced a greater reduction in the latency to and a greater prolongation of the duration of pentobarbital-induced loss of the righting reflex. LMP-melatonin produced greater formulation-dependent effects than conventional melatonin on caffeine-evoked cortical electrical activity, pentobarbital-induced sedative-hypnotic responses, and selected biochemical and molecular outcomes. However, pharmacokinetic exposure, physiological sleep stages, sleep architecture, sleep quality, and direct measures of neuronal injury were not assessed. Therefore, the findings do not directly establish enhanced bioavailability, physiological sleep promotion, or neuroprotection.
- MakaleAçık Erişim2026Scopus SJRQ2Synergistic Effects of Caffeine and Paclitaxel in Breast Cancer Cells: Mechanistic Insights Into NF-κB and Nrf2 Signaling
Gencoglu, Hasan; Delioglu, Saime; Nergiz, Mehmet Akif; Metin, Rumeysa; Erten, Fusun; Tokmak, Muhammed; Orhan, Cemal; Sahin, Kazim
Breast cancer remains one of the most prevalent malignancies among women. Recent studies have explored the potential of phytochemicals such as caffeine as chemosensitizing agents in enhancing the efficacy of standard chemotherapeutics like paclitaxel. This study aimed to investigate the cytotoxic, apoptotic, inflammatory, and oxidative stress-related effects of caffeine alone and in combination with paclitaxel in MCF-7 cells. Cells were treated with various concentrations of caffeine (1–100 mM), paclitaxel (0–350 µg/mL), and their combinations for 24, 48, and 72 h. Cell viability was assessed using the MTS assay, and IC₅₀ values were calculated. The expression levels of Bax, Bcl-2, NF-κB, and Nrf2 proteins were analyzed by Western blotting. Both caffeine and paclitaxel induced time- and dose-dependent reductions in MCF-7 cell viability. The combination treatment showed synergistic cytotoxicity, with significantly lower IC₅₀ values compared to single-agent treatments. Western blot analysis showed that both treatments boosted pro-apoptotic Bax and decreased anti-apoptotic Bcl-2, with slightly less effect in the combination group. NF-κB levels increased considerably in caffeine and paclitaxel groups, but were lower in the combination group compared to paclitaxel alone, suggesting a possible reduction in inflammatory signaling. Nrf2 expression increased significantly with caffeine, suggesting oxidative stress responses. In MCF-7 cells, caffeine enhanced paclitaxel's pro-apoptotic and cytotoxic actions and modified inflammation and oxidative stress pathways in a complicated, dose-dependent manner. Cytotoxicity was synergistic; however, apoptotic and stress indicators may be antagonistic. In clinical circumstances, caffeine may be an adjuvant in breast cancer treatment, however mechanistic and in vivo investigations are needed.
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İncele - MakaleAçık Erişim2026Scopus SJRQ1Modulation of SIRT1/PPARγ pathways and tight junction proteins by nicotinamide riboside under chronic variable stress
Celik, Abdullah; Sahin, Nurhan; Orhan, Cemal; Er, Besir; Erten, Fusun; Ozmen, Busra; Tuzcu, Mehmet; Ozercan, Ibrahim Hanifi; Sahin, Kazim
Abstract: Chronic stress disrupts homeostasis, leading to major health problems such as liver damage, intestinal barrier dysfunction, and impaired glucose metabolism. Although current treatments, including anxiolytics, sedatives, antidepressants, and beta blockers, are effective, their adverse effects emphasize the need for safer alternatives. Nicotinamide riboside (NR), a precursor of nicotinamide adenine dinucleotide (NAD+), plays a central role in energy metabolism and oxidative stress regulation; elevated NAD + levels have been associated with reduced risk of chronic diseases such as obesity and type 2 diabetes. However, the effects of NR on liver metabolism, intestinal barrier integrity, and related protein pathways remain unclear. This study investigated the effects of NR supplementation in rats exposed to chronic variable stress (CVS). Fifty-six male Sprague Dawley rats were divided into normal and CVS groups and treated in a 2 × 4 factorial design with 0, 150, 300, or 600 mg/kg NR. Under CVS conditions, serum glucose, corticosterone, ACTH, and insulin levels increased, whereas NAD+, NADPH, nicotinamide (NAM), and nicotinic acid (NA) decreased significantly (p < 0.001). NR supplementation effectively corrected these biochemical imbalances and upregulated hepatic markers, including PPARγ, SIRT1, GLUT2, IRS1, and FASN (p < 0.001). Furthermore, the increased expression of key transport proteins such as PepT1, LAT2, EAAT3, FABP2, and FATP4 contributed to maintaining intestinal barrier integrity and improving gut health. NR also promoted the recovery of tight and adherens junction proteins. Notably, high-dose NR (600 mg/kg) markedly alleviated liver fibrosis, improved glucose metabolism, and strengthened intestinal barrier function, demonstrating its therapeutic potential as an alternative strategy against stress-induced metabolic disorders. Key points: • NR mitigated chronic stress-induced liver, intestinal, and glucose dysregulation. • NR improved glycemia and NAD⁺-related biomarkers under stress. • NR reduced hepatic fibrosis markers. • NR strengthened TJ/AJ proteins, supporting intestinal barrier integrity. • Findings support NR’s therapeutic potential in stress-related metabolism.
- MakaleAçık Erişim2026Scopus SJRQ2Water extracts of Fucus vesiculosus and Laminaria digitata enhance male reproductive parameters via antioxidant and NO/cGMP mechanisms in rats
Gencoglu, Hasan; Erten, Fusun; Er, Besir; Orhan, Cemal; Acisu, Tutku Can; Sahin, Kazim
Male sexual dysfunction is increasingly prevalent, driving interest in marine algal bioactives as potential natural modulators of reproductive physiology. Brown seaweeds such as Fucus vesiculosus and Laminaria digitata contain phlorotannins, fucoidans, and antioxidant compounds of applied relevance in phycology and biotechnology. This study assessed the effects of standardized water extracts of these two species on reproductive behavior, hormonal status, sperm quality, oxidative balance, and nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling in male Sprague–Dawley rats. Animals received the seaweed extracts orally by gavage (300 mg kg⁻1 day⁻1) for 52 days. Both extracts improved male reproductive behavior by reducing the time required to initiate mounting, intromission, and ejaculation (mount latency, intromission latency, and ejaculation latency), while increasing the number of these sexual behaviors during the test period (p < 0.05). Serum follicle-stimulating hormone and testosterone concentrations increased, alongside higher testicular superoxide dismutase, catalase, and glutathione peroxidase activities and lower malondialdehyde levels. Sperm count and motility improved, particularly with L. digitata extract. Western blot analyses revealed phosphorylated phosphodiesterase-5, endothelial NO synthase, and cGMP levels, with reduced endothelin-1 in testicular and epididymal tissues (p < 0.05–0.001). These findings indicate that extracts of F. vesiculosus and L. digitata, chosen for their well-documented antioxidant and phlorotannin-rich profiles, confer protective and prosexual effects associated with enhanced antioxidant defense and upregulation of NO/cGMP-related pathways, with the L. digitata extract exhibiting comparatively stronger activity.
- MakaleYayıncıda açık erişim2026Scopus SJRQ1tVNS Mitigates Neuroinflammation and Nociception in a Rodent LPS Endotoxemia Model
Atalar, Kerem; Alim, Ece; Calikusu, Aysen; Abbasoglu Topa, Elif Gulcicek; Gok Dagidir, Hale; Bahcelioglu, Meltem; Bukan, Neslihan; Erten, Fusun; Sahin, Kazım; Akarca Dizakar, Saadet Özen
The vagus nerve plays a modulatory role in the gut-brain axis. Intestinal barrier dysfunction and lipopolysaccharide (LPS) leakage into the systemic circulation are associated with several conditions, such as irritable bowel syndrome (IBS) and migraine headache. This study investigates the impact of non-invasive transauricular vagus nerve stimulation (tVNS) on the neuroinflammatory markers and pain behavior following an acute LPS challenge. Sprague–Dawley rats (n = 28) were given LPS or vehicle and subjected to tVNS or sham intervention in an acute LPS animal model that mimics the systemic consequences of barrier dysfunction. Behaviors were evaluated at the baseline and 6 h later, complemented by testing the levels of serum and brain neuroinflammatory markers. Behavioral analyses revealed that LPS exposure reduced the time spent in the open arm, grooming duration, and periorbital mechanical pain thresholds, and increased freezing duration. The tVNS intervention reversed these behavioral changes induced by LPS. LPS administration triggered elevated serum levels of IL-6, CGRP, haptoglobin, and VE-cadherin. LPS also increased IL-1β, PAR-2, haptoglobin, CGRP, and HMGB1 levels in the brain tissue. The tVNS intervention reversed the effects observed in the brain, but it did not change the elevated levels of inflammatory molecules in the systemic circulation. tVNS has the potential to modulate neuroimmune interactions, with an early impact on the brain during LPS surge. tVNS may have potential therapeutic benefits in managing pain-related disorders associated with LPS endotoxemia.
- Derleme MakaleAçık Erişim2026Scopus SJRQ1Nutraceuticals in Uro-Oncology: A Structured Expert Review and Precision-Oriented Framework
Erten, Fusun; Kalemoglu, Ecem; Kucuk, Omer; Sahin, Kazim
Urologic malignancies (UMs), including prostate cancer (PCa), bladder cancer (BCa), renal cell carcinoma (RCC), and testicular germ cell tumors (TGCT), are governed by interconnected molecular pathways that regulate proliferation, angiogenesis, metabolism, invasion, immune escape, and treatment resistance. Key pathways include PI3K/AKT/mTOR, VEGF/VEGFR, EGFR, FGFR, c-MET, androgen receptor signaling, DNA damage response, inflammatory transcriptional programs, and regulation of the tumor microenvironment. This structured expert review evaluates mechanistic, translational, epidemiological, and clinical evidence on food- and botanical-derived nutraceuticals that may influence cancer-related signaling, redox balance, inflammation, metabolic adaptation, and host–tumor interactions. Nutraceuticals are considered investigational adjunctive exposures rather than anticancer treatments or alternatives to standard care. Relevant literature was identified through a structured, non-systematic search of PubMed/MEDLINE, Scopus, Web of Science Core Collection, and Embase from database inception to 17 June 2026, supplemented by backward and forward citation searches. Eligible evidence comprised preclinical, observational, interventional, pharmacokinetic, formulation, safety, and drug–nutraceutical interaction studies. Evidence was evaluated by cancer type, compound class, molecular context, formulation, exposure, translational maturity, and safety, and was classified into five stages: prevention signal, mechanistic plausibility, bioavailability and exposure feasibility, exposure-linked biomarker activity, and clinical benefit. An exposure–species–compartment framework was used to assess whether parent compounds and relevant metabolites reached systemic, urinary, or target-tissue concentrations compatible with the proposed effects. Findings based solely on supraphysiological concentrations of unconjugated parent compounds were considered hypothesis-generating unless supported by human exposure or tissue-distribution data. Curcumin, green tea catechins, isoflavones, carotenoids, flavonols, stilbenes, and triterpenoids affect several cancer-related pathways, primarily in experimental models. Translation to clinical practice is constrained by inconsistent formulations, limited bioavailability, inadequate target-tissue exposure data, few biomarker-linked studies, and possible interactions with anticancer therapies. PCa and BCa provide the most suitable settings for exposure-verified mechanistic studies. In RCC, safety and treatment interactions should be prioritized, whereas in TGCTs, non-interference with curative cisplatin-based therapy must be demonstrated. Future studies should use chemically defined formulations, verify clinically relevant exposure, incorporate mechanism-matched biological-response endpoints, and confirm compatibility with established treatment. Current evidence does not support nutraceuticals as treatments for urologic malignancies.
- MakaleYalnız künye2026Scopus SJRQ1Boron source–dependent regulation of bone mineralization and osteogenic molecular pathways in broilers with tibial dyschondroplasia
Orhan, Cemal; Sahin, Emre; Erten, Fusun; Er, Besir; Sahin, Nurhan; Ozercan, Ibrahim Hanifi; Kom, Mustafa; Akdemir, Fatih; Balci, Tansel Ansal; Denli, Muzaffer
Rapid genetic selection for growth rate and slaughter weight in broilers has been associated with a higher incidence of skeletal disorders, particularly tibial dyschondroplasia (TD), which causes considerable economic losses in poultry production. We investigated the effects of boric acid (BA) and sodium pentaborate pentahydrate (SPP) on growth performance, bone mineralization, tibial histopathology, and osteogenic protein expression in broilers with manganese (Mn) deficiency-induced TD. A total of 360 Ross 308 broiler chicks were used in a 2 × 2 × 3 factorial design with TD status (normal or Mn deficiency–induced TD), boron source (BA or SPP), and supplemental boron level (0, 4.37, and 8.74 mg elemental B/kg diet). Birds were randomly allocated to 12 groups with six replicates of five birds each. Clinical and histopathological findings confirmed TD induction. TD decreased body weight, feed intake, and carcass weight, while increasing feed conversion ratio (p < 0.05). Boron supplementation improved tibial mineral density and content in a dose-dependent manner (p < 0.05). In TD broilers, serum osteocalcin (OCN) concentrations were higher with high-level SPP supplementation than with BA supplementation (p = 0.012). Boron source and level significantly affected serum and bone boron concentrations, bone calcium concentrations (p < 0.05). In TD broilers, tibial osteoprotegerin levels were markedly elevated in the high-level SPP group (p < 0.001), whereas SRY-box transcription factor 9, hypoxia-inducible factor-1α, and tumor necrosis factor-α were reduced (p < 0.05). These findings indicate that SPP exerts regulatory effects on bone metabolism and osteogenic signaling pathways in TD-affected broilers.
- MakaleAçık Erişim2025Scopus SJRQ3EFFECTS OF LACTOBACILLUS PLANTARUM ON THE AKT/ENOS CARDIAC PATHWAY IN RATS WITH FRUCTOSE-INDUCED METABOLIC SYNDROME
Kursun, Oznur Ece Durmaz; Yalim, Goknur; Demirel, Murside Ayse; Erten, Fusun; Sahin, Kazim; Akar, Fatma
Background. This study investigated the effects of Lactobacillus plantarum supplementation on the Akt/eNOS pathway in the cardiac tissue of rats subjected to a fructose-rich diet, which induced metabolic syndrome. Materials and methods. Twenty-two male Wistar albino rats were randomly assigned to three groups: (1) control, (2) fructose, and (3) fructose ± L. plantarum. Rats in the fructose group were administered a 20% fructose solution in their drinking water for 15 weeks. In the L. plantarum-treated group, the probiotic was administered via gastric gavage at a daily dose of 1×109 CFU/mL/100 g during the final six weeks of the study. Results. The administration of Lactobacillus plantarum resulted in a significant increase in the levels of Akt (p < 0.0001), IRS-1 (p = 0.0113), mTOR (p < 0.0001), eNOS (p < 0.0001), and SIRT1 (p = 0.0031) in the cardiac tissue of rats compared to the fructose group. Moreover, a marked reduction in iNOS, NF-κB, and TNF-α levels (p < 0.0001) was observed, highlighting the potential of L. plantarum to counteract the adverse effects of fructose consumption. Conclusion. The findings of this study suggest that L. plantarum has the potential to reduce inflammation in the heart, enhance insulin sensitivity via the Akt/eNOS pathway, and protect against cardiovascular diseases associated with metabolic syndrome.
- MakaleAçık Erişim2025Scopus SJRQ1Transauricular vagal nerve stimulation suppresses inflammatory responses in the gut and brain in an inflammatory bowel disease model
Atalar, Kerem; Alim, Ece; Yigman, Zeynep; Belen, Hayrunnisa Bolay; Erten, Fusun; Sahin, Kazım; Soylu, Ayse; Dizakar, Saadet Ozen Akarca; Bahcelioglu, Meltem
Inflammatory bowel disease (IBD) encompasses Crohn's disease (CD) and ulcerative colitis (UC), is a major health problem on a global scale and its treatment is unsatisfactory. We aimed to investigate the effects of transauricular vagal nerve stimulation (tVNS) on inflammation in rats with IBD induced by trinitrobenzene sulfonic acid (TNBS). A total of 36 adult female Sprague–Dawley rats were given TNBS, or vehicle, and tVNS, or sham, every other day for 30 min for 10 days. Postmortem macroscopic and microscopic colon morphology were evaluated by histological staining. Additionally, IL-1β, IL-6, IL-10, and TNF-α cytokine levels in the colon and the brain were evaluated by immunohistochemistry and western blotting analysis. TNBS induced epithelial damage, inflammation, ulceration, and thickened mucosal layer in the colonic tissues. Administration of tVNS significantly ameliorated the severity of TNBS-induced tissue damage and inflammatory response. TNBS also alters pro-inflammatory and anti-inflammatory balance in the brain tissue. TVNS application significantly suppressed the protein levels of pro-inflammatory cytokines, namely IL-1β, IL-6, and TNF- α while augmenting the level of anti-inflammatory cytokine IL-10 in the colonic and the brain tissue. We have shown that TNBS-mediated colonic inflammation and tissue damage are associated with neuroinflammatory responses in the brain tissue. Also demonstrated for the first time that neuroinflammatory response in the gut-brain axis is suppressed by tVNS in the IBD model. Non-invasive tVNS stands out as a new potential treatment option for types of IBD.
AtıfScopus13OpenAlex12İncele - MakaleAçık Erişim2025Scopus SJRQ1Effects of Integrated Extracts of Trigonella foenum-graecum and Asparagus racemosus on Hot Flash-like Symptoms in Ovariectomized Rats
Erten, Fusun; Er, Besir; Ozmen, Ramazan; Tokmak, Muhammed; Gokdere, Ebru; Orhan, Cemal; Morde, Abhijeet A.; Padigaru, Muralidhara; Sahin, Kazim
Vasomotor symptoms, such as hot flashes (HFs), commonly affect women during menopause, leading to a reduced quality of life. The current study evaluates the combined effect of active components Asparagus racemosus (AR) and Trigonella foenum-graecum (TFG) in a single oral formulation (IAT) for alleviating menopausal symptoms in ovariectomized rats. Following bilateral ovariectomy, the animals were randomly assigned to nine groups: (1) Control, (2) Ovariectomy (OVX), (3) OVX+TA1 (TA: Combination of Trigonella and Asparagus; TFG 30 mg/kg + AR 30 mg/kg), (4) OVX+TA2 (TFG 30 mg/kg + AR 15 mg/kg), (5) OVX+TA3 (TFG 15 mg/kg + AR 30 mg/kg), (6) OVX+TA4 (TFG 40 mg/kg + AR 30 mg/kg), (7) OVX+TA5 (TFG 30 mg/kg + AR 40 mg/kg), (8) OVX+IAT1 (IAT: Integrated Asparagus and Trigonella; TFG+AR integrated extract, 30 mg/kg), and (9) OVX+IAT2 (TFG+AR integrated extract, 60 mg/kg). On the 8th day of treatment, tail and skin temperatures were recorded every 30 min for 24 h. Ovariectomized rats exhibited menopausal symptoms, such as hormonal imbalances and elevated skin temperature. Administration of AR, TFG, and IAT significantly decreased serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and cortisol while increasing estradiol, progesterone, and dopamine (p < 0.0001), effectively alleviating hot flash-like symptoms. Additionally, they mitigated ovariectomy-induced oxidative stress by lowering malondialdehyde (MDA) levels and restoring antioxidant enzyme activity. Ovariectomized rats exhibited increased expression of a proto-oncogene (c-FOS), gonadotropin-releasing hormone (GnRH), Kisspeptin, Neurokinin B (NKB), and Transient receptor potential vanilloid 1 (TRPV1), along with reduced expressing brain-derived neurotrophic factor (BDNF) levels, which were reversed by treatment, especially with the IAT2 combination. The AR and TFG combination, particularly in IAT formulations, showed strong potential in alleviating menopausal symptoms in ovariectomized rats. These findings suggest that the combination of AR and TFG extracts could be a natural alternative for managing postmenopausal symptoms by restoring reproductive hormone levels, regulating lipid profiles, and enhancing antioxidant defense systems.
AtıfScopus8WoS8OpenAlex6İncele - MakaleAçık Erişim2024Scopus SJRQ1Novel formulations ameliorate osteoarthritis in rats by inhibiting inflammation and oxidative stress
Erten, Fusun; Ozdemir, Oguzhan; Tokmak, Muhammed; Durmus, Ali Said; Ozercan, Ibrahim Hanifi; Morde, Abhijeet; Padigaru, Muralidhara; Sahin, Kazim
The study tested new oral plant-based formulations (F) on rats with monosodium iodoacetate (MIA)-induced osteoarthritis, measuring inflammation, antioxidant levels, paw size, stride, and analyzing knee joint images. Fifty-six female Sprague Dawley rats were allocated into 8 groups: (1) Control, (2) MIA (OA induced with MIA), (3) MIA + F1 [curcuminoids+gingerols+acetyl-11-keto-β boswellic acid (AKBA)], (4) MIA + F2 (curcuminoids+Withania glycosides+AKBA), (5) MIA + F3 (curcuminoids+total withanolides+AKBA), (6) MIA + F4 (curcuminoids, AKBA), (7) MIA + UCII (type II collagen), and (8) MIA + GCHON (Glucosamine Chondroitin). Treatments F1 to F4 reduced right joint diameter and improved stride length and paw area in OA rats. Despite improvements with treatments F1 to F4, there was no significant difference between these groups (p >.05). In OA animals, F1 to F4 treatments decreased MDA levels and increased antioxidant enzymes activities (p <.001). This was done by reducing levels of inflammatory markers and enzymes like IL-1β, IL-6, MMP-8, TNF-α, CRP, COMP, and LOX-5, while increasing the anti-inflammatory cytokine IL-10. In conclusion, these plant-based treatments significantly reduced osteoarthritis severity, slowed disease progression by reducing inflammation, and protected joints from damage, showing a protective effect in rats with induced osteoarthritis, likely due to their anti-inflammatory and antioxidant properties.
AtıfScopus14WoS11OpenAlex10İncele - MakaleAçık Erişim2024Scopus SJRQ1Impact of a Novel Valerian Extract on Sleep Quality, Relaxation, and GABA/Serotonin Receptor Activity in a Murine Model
Sahin, Kazim; Gencoglu, Hasan; Korkusuz, Ahmet Kayhan; Orhan, Cemal; Aldatmaz, İsmail Ertuğ; Erten, Fusun; Er, Besir; Morde, Abhijeet; Padigaru, Muralidhara; Kilic, Ertugrul
Insomnia is a major global health issue, highlighting the need for treatments that are both effective and safe. Valerian extract, a traditional remedy for sleep problems, offers potential therapeutic options. This research examined the potential sleep-enhancing effects of VA (Valerian Pdr%2) in mice. The study evaluated sleep quality by comparing the impact of the VA extract against melatonin on brain activity, using electrocorticography (ECoG) to assess changes in brain waves. For this purpose, the study utilized two experimental models on BALB/c mice to explore the effects of caffeine-induced insomnia and pentobarbital-induced sleep. In the first model, 25 mice were assigned to five groups to test the effects of caffeine (caffeine, 7.5 mg/kg i.p) alone, caffeine with melatonin (2 mg/kg), or caffeine with different doses of valerian extract (100 or 300 mg/kg) given orally on brain activity, assessed via electrocorticography (ECoG) and further analyses on the receptor proteins and neurotransmitters. In the second model, a different set of 25 mice were divided into five groups to examine the impact of pentobarbital (42 mg/kg) alone, with melatonin, or with the valerian extract on sleep induction, observing the effects 45 min after administration. The study found that ECoG frequencies were lower in groups treated with melatonin and two doses of valerian extract (100 and 300 mg/kg), with 300 mg/kg showing the most significant effect in reducing frequencies compared to the caffeine control group, indicating enhanced sleep quality (p < 0.05). This was supported by increased levels of serotonin, melatonin, and dopamine and higher levels of certain brain receptors in the melatonin and valerian extract groups (p < 0.05). Modulatory efficacy for the apoptotic markers in the brain was also noted (p < 0.05). Additionally, melatonin and both doses of VA increased sleep duration and reduced sleep onset time compared to the pentobarbital control, which was particularly notable with high doses. In conclusion, the findings suggest that high doses (300 mg/kg) of valerian extract enhance both the quantity and quality of sleep through the GABAergic pathway and effectively increase sleep duration while reducing the time to fall asleep in a pentobarbital-induced sleep model in mice.
AtıfScopus19OpenAlex19İncele - MakaleAçık Erişim2023Scopus SJRQ1Effects of a Combination of Arginine Silicate Inositol Complex and a Novel Form of Biotin on Hair and Nail Growth in a Rodent Model
Demir, Betul; Cicek, Demet; Orhan, Cemal; Er, Besir; Erten, Fusun; Tuzcu, Mehmet; Ozercan, Ibrahim Hanifi; Sahin, Nurhan; Komorowski, James; Ojalvo, Sara Perez
The purpose of this study was to examine the effects of a combination of inositol-stabilized arginine silicate complex (ASI) and magnesium biotinate (MgB) on hair and nail growth in an animal model. Twenty-eight female Sprague–Dawley rats (8 weeks old) were randomized into one of the following groups: (i) group (control), shaved; (ii) group (ASI), shaved + ASI (4.14 mg/rat/day); (iii) group (ASI + MgB I), shaved + ASI (4.14 mg/rat/day) + MgB (48.7 μg/rat/day); and (iv) group (ASI + MgB II), shaved + ASI (4.14 mg/rat/day) + MgB (325 μg/rat/day). On day 42, compared with the control group, while hair density (p < 0.05, p < 0.01, and p < 0.0001, respectively) and anagen ratio (p < 0.01, p < 0.01, and p < 0.001) increased in the ASI, ASI + MgB I, and ASI + MgB II groups, telogen ratio decreased (p < 0.01, p < 0.01, and p < 0.001, respectively). In the molecular analysis, VEGF, HGF, and KGF-2 increased in the ASI (p < 0.01, p < 0.01, and p < 0.05, respectively), ASI + MgB I (p < 0.0001 for all), and ASI + MgB II (p < 0.0001 for all) groups when compared to the control group. FGF-2 (p < 0.01) and IGF-1 (p < 0.001) were found to be increased in the ASI + MgB I and ASI + MgB II groups. SIRT-1 and β-catenin increased in the ASI (p < 0.05 and p < 0.01), ASI + MgB I (p < 0.001 for both), and ASI + MgB II (p < 0.0001 for both) groups. Wnt-1 increased in the ASI + MgB I (p < 0.001) and ASI + MgB II (p < 0.0001) groups. In conclusion, the combination of ASI and MgB could promote hair growth by regulating IGF-1, FGF, KGF, HGF, VEGF, SIRT-1, Wnt, and β-catenin signal pathways. It was also established that ASI did not affect nail growth, whereas the MgB combination was effective using a higher dose of biotin.
AtıfScopus11WoS9OpenAlex11İncele - MakaleAçık Erişim2023Scopus SJRQ1Evaluation of pea/rice and amylopectin/chromium as an alternative protein source to improve muscle protein synthesis in rats
Ozdemir, Oguzhan; Erten, Fusun; Er, Besir; Orhan, Cemal; Komorowski, James R.; Sylla, Sarah; Perez Ojalvo, Sara; Sahin, Kazim
Background: A preclinical study reported that the combination of an amylopectin/chromium complex (ACr) of branched-chain amino acids (BCAA) significantly enhanced muscle protein synthesis (MPS). This study was conducted to determine the effects of the addition of ACr complex to a pea/rice (PR) protein on MPS, insulin, muslin levels, and the mTOR pathway in exercised rats. Methods: Twenty-four rats were divided into three groups: (i) exercise (Ex); (ii) Ex + PR 1:1 blend (0.465 g/kg BW); (iii) Ex + PR + ACr (0.155 g/kg BW). On the day of single-dose administration, after the animals were exercised at 26/m/min for 2 h, the supplement was given by oral gavage. The rats were injected with a bolus dose (250 mg/kg BW, 25 g/L) of deuterium-labeled phenylalanine to determine the protein fractional synthesis rate (FSR) one h after consuming the study product. Results: The combination of PR and ACr enhanced MPS by 42.55% compared to the Ex group, while Ex + PR alone increased MPS by 30.2% over the Ex group (p < 0.0001) in exercised rats. Ex + PR plus ACr significantly enhanced phosphorylation of mTOR and S6K1 (p < 0.0001), and 4E-BP1 (p < 0.001) compared to the Ex (p < 0.0001). PR to ACr also significantly increased insulin and musclin levels (p < 0.0001) in exercised rats. Additionally, compared to Ex + PR alone, Ex + PR + ACr enhanced mTOR (p < 0.0001) and S6K1 (p < 0.0001) levels. Conclusion: These data suggested that PR + ACr may provide an alternative to animal proteins for remodeling and repairing muscle by stimulating MPS and mTOR signaling pathways in post-exercised rats. More preclinical and clinical human studies on combining pea/rice and amylopectin/chromium complex are required.
AtıfScopus4OpenAlex4İncele - MakaleAçık Erişim2023Scopus SJRQ1The effect of oral administration of undenatured type II collagen on monosodium iodoacetate-induced osteoarthritis in young and old rats
Sahin, Emre; Orhan, Cemal; Erten, Fusun; Saiyed, Zainulabedin; Azari, Elnaz Karimian; Durkee, Shane; Sahin, Kazim
We investigated whether different doses of undenatured type II collagen (undenatured collagen, UC-II) help improve monosodium iodoacetate (MIA)-induced (osteoarthritis) OA in young and old rats. A total of 70 rats were divided into five groups: (1) control; (2) MIA (a single intra-articular injection of MIA); (3)–(5) MIA+ Undenatured Collagen with various oral doses (0.66, 1.33, and 2 mg/kg). The results showed that all doses of undenatured collagen in both age groups reduced knee diameter, while the two higher doses (1.33 mg/kg and 2 mg/kg) reduced the Mankin score and increased most gait measurements as early as day 14 compared to the MIA rats. However, the 2 mg/kg dose showed the best efficacy in improving Mankin score and gait measurements by 28 days post-OA induction. In young but not old rats, all doses of undenatured collagen reduced the Kellgren-Lawrence score compared to the MIA group. Undenatured collagen reduced the levels of most inflammatory and cartilage breakdown markers in serum and knee joint cartilage in both age groups. In conclusion, this data suggests that while all doses of undenatured collagen supplementation may ameliorate MIA-induced OA symptoms, the higher doses showed faster improvement in gait measurements and were more efficacious for overall joint health in rats.
AtıfScopus17WoS17OpenAlex15İncele - MakaleAçık Erişim2023Scopus SJRQ1Lutein/Zeaxanthin Isomers and Quercetagetin Combination Safeguards the Retina from Photo-Oxidative Damage by Modulating Neuroplasticity Markers and the Nrf2 Pathway
Sahin, Emre; Orhan, Cemal; Sahin, Nurhan; Padigaru, Muralidhara; Morde, Abhijeet; Lal, Mohan; Dhavan, Nanasaheb; Erten, Fusun; Bilgic, Ahmet Alp; Ozercan, Ibrahim Hanifi
Exposure to light-emitting diode (LED) light is a primary cause of retinal damage, resulting in vision loss. Several plant-derived substances, such as lutein and quercetagetin (QCG), show promise in supporting eye health. In this study, the impact of lutein/zeaxanthin (L/Z, Lutemax 2020) and QCG were evaluated individually and together in a rat model of LED-induced retinal damage. A total of 63 Wistar rats were allocated into nine groups (n = 7). For 28 days, the rats received L/Z (10 or 20 mg/kg BW), quercetin (QC, 20 mg/kg BW), QCG (10 or 20 mg/kg BW), or a mixture of different lutein and QCG dosages, after which they were exposed to LED light for 48 h. LED exposure led to a spike in serum malondialdehyde (MDA) and inflammatory cytokines, as well as an increase in retinal NF-κB, ICAM, GFAP, and MCP-1 levels (p < 0.0001 for all). It also reduced serum antioxidant enzyme activities and retinal Nrf2, HO-1, GAP43, NCAM, and outer nuclear layer (ONL) thickness (p < 0.0001 for all). However, administering L/Z and QCG, particularly a 1:1 combination of L/Z and QCG at 20 mg/kg, effectively reversed these changes. The treatment suppressed NF-κB, ICAM, GFAP, and MCP-1 while enhancing Nrf2, HO-1, GAP43, and NCAM and preventing ONL thickness reduction in LED-induced retinal damage rats. In conclusion, while LED light exposure caused retinal damage, treatment with L/Z, QC, and QCG, particularly a combined L/Z and QCG regimen, exhibited protective effects on the retina. This is possibly due to the modulation of neuroplasticity markers and nuclear transcription factors in the rats’ retinal cells.
AtıfScopus22OpenAlex22İncele - MakaleYalnız künye2022Fucus vesiculosus ve Laminaria digitata Ekstraktlarının \rProstat ve Seminal Vezikül p-PDE5, cGMP, eNOS ve ET-1 \rDüzeyleri Üzerine Etkileri
Sahin, Kazim; Er, Besir; Erten, Fusun
Üreme sağlığı yaşam kalitesinin önemli belirteçlerinden biridir. Günümüzde erkek bireylerde düşük \rlibido, erektil disfonksiyon, prematür ejakülasyon, gecikmiş veya inhibe orgazm gibi cinsel işlev \rbozuklukları giderek yaygın hale gelmektedir. Cinsel işlev bozukluklarının tedavisi için destek \rtedaviler arasında fito ve etnoterapiler günümüz dünyasında popülerlik kazanmaktadır. Fucus \rvesiculosus (FV) ve Laminaria digitata (LD), antioksidan, anti-tümör, antikoagülan, anti obezitik, \ranti inflamatuar, antiviral ve antibakteriyel aktivitelere sahiptirler. Bu çalışmanın amacı, FV ve LD\rekstraktlarının üzerine prostat ve seminal vezikül dokularında fosfodiesteraz tip 5 (p-PDE5), siklik \rguanozin monofosfat (cGMP), endotel nitrik oksit sentaz (eNOS) ve endotelin‑1 (ET-1) protein \rdüzeyleri üzerine etkilerini araştırmaktır. Çalışmada, toplam 21 adet erkek 12 haftalık SpragueDawley ırkı sıçan kullanıldı. Sıçanlar üç gruba ayrıldı: 1) Kontrol grubu, 2) FV grubu ve 3) LD \rgrubu. FV ve LD 300 mg/kg CA dozunda gavaj yoluyla 52 gün boyunca günlük olarak hayvanlara \rverildi. Prostat dokusunda kontrol grubuna göre, FV ve LD verilen gruplarda p-PDE5 (P<0.01), \rcGMP (P<0.001) ve eNOS (P<0.05) düzeylerinde artış gözlenirken, ET-1 (P<0.01) protein \rdüzeyinde düşüş tespit edildi. Benzer şekilde seminal vezikül dokusunda da p-PDE5 (P<0.001) ve \reNOS (P<0.001) artış, cGMP (P<0.01) ise sadece LD verilen grupta artış gözlendi. Seminal vezikül \rET-1 (P<0.001) düzeyinde ise prostat dokusuyla benzer şekilde düşüş görüldü. Sonuç olarak, FV\rve LD ekstraktlarının p-PDE5, cGMP ve eNOS, ET-1 sinyal yolaklarını regüle ederek cinsel işlev \rbozuklukları üzerine yararlı etkiler gösterebileceği düşünülmektedir.
- MakaleYalnız künye2022Effects of Maca Root Extract on Some Molecular Parameters of Kidney Tissue in Rats Fed a High-Fat Diet
Erten, Fusun
Maca (Lepidium meyenii) has been used as a dietary supplement in ethnomedicine for centuries.\rMaca has recently become a high-functional food globally, due to its numerous biological benefits.\rThe high-fat diet (HFD) is closely related to the occurrence of obesity. Obesity is a common cause\rfor chronic kidney disease. The aim of this study was to investigate the effects of maca on organic\ranion transporters-3 (OAT-3), organic cation transporter-1 (OCT-1), organic cation transporter-2\r(OCT-2), insulin receptor substrate-1(IRS-1), vascular adhesion molecule-1 (VCAM-1) and\rvascular endothelial growth factor (VEGF) protein levels. In the study, 28 Sprague-Dawley male\rrats were randomly allocated into four groups (n=7); i) Control group (fed with standard diet); ii)\rGroup fed with standard diet and supplemented with Maca (40mg/kg/day) group; iii) Group fed a\rHFD; iv) Group fed with Maca+HFD. After the 60-day of study, kidney OCT-1, OCT-2 and IRS-1\rprotein levels showed a significant increase in the HFD+Maca treated group compared to the HFD\rgroup (P<0.05). Renal OAT-3 level was found to be significantly lower in the HFD group compared\rto the control group (P<0.0001). In addition, a significant decrease in VCAM-1 and VEGF protein\rlevels was observed in the HFD+Maca group compared to the HFD group (P<0.0001). These\rresults show the protective and regulatory activity in the Maca's kidney tissue when both normally\rand the HFD diet is fed
- MakaleYalnız künye2022Effect of Lutein/Zeaxanthin Isomers on the Musclin Signaling Pathway
Sahin, Kazim; Er, Besir; Erten, Fusun
Lutein (L) and zeaxanthin (Zi) are plant origin carotenoids. They have anti-inflammatory and\rantioxidant effects. Musclin is a myokine induced by physical activity. The aim of this study was to\rinvestigate the effect of L/Zi supplementation on serum and skeletal muscle musclin levels in rats\rsubjected to physical exercise. For this purpose, the rats were divided into four groups, each\rconsisting of seven rats, as the control group, no exercise, L/Zi treated and no exercise group\r(L/Zi), exercise group (E), and L/Zi treated and exercise group (E + L/Zi treatment). L/Zi was\radministered daily for eight weeks as an oral supplement by gavage at a dose level of 100 mg/kg\rBW. When compared with control, E, L/Zi and E + L/Zi decreased muscle triglyceride level by\r30.8%, 28.3% and 57.4%, respectively and increased serum and muscle musclin levels by 58.03%,\r67.4%, 136.5% and 49.4%, 50.1%, 85.6% respectively. In conclusion, it was determined that\rskeletal muscle and systemic musclin levels were stimulated by L/Zi combination in rats subjected\rto chronic exercise
- MakaleYayıncıda açık erişim2021Scopus SJRQ4Effects of magnesium biotinate supplementation on serum insulin, glucose and lipid parameters along with liver protein levels of lipid metabolism in rats
Sahin, Kazim; Orhan, Cemal; Kucuk, Osman; Erten, Fusun; Tuzcu, Mehmet; Sahin, Nurhan; Ojalvo, Sara Perez; Komorowski, James Richard
The objective of this study was to investigate the effects of a novel form of biotin (magnesium biotinate) on serum glucose, lipid profile, and hepatic lipid metabolism-related protein levels in rats. Forty-two rats were divided into six groups and fed a standard diet-based egg white powdered diet supplemented with either d-biotin at 0.01, 1, or 100 mg/kg BW or magnesium biotinate at 0.01, 1, or 100 mg/kg BW for 35 days. Neither form of biotin influenced (p > 0.05) serum glucose or insulin concentrations. Serum total cholesterol and triglyceride decreased with biotin from both sources (p < 0.05). Concentrations were lower with magnesium biotinate when comparing the 1 mg/kg dose (p < 0.05). Serum, liver, and brain biotin and liver cyclic guanosine monophosphate (cGMP) concentrations were greater when rats were treated with magnesium biotinate versus d-biotin, particularly when comparing the 1 and 100 mg/kg dose groups (p < 0.05). Both biotin forms decreased the liver SREBP-1c and FAS and increased AMPK-a1, ACC-1, ACC-2, PCC, and MCC levels (p < 0.05). The magnitudes of responses were more emphasized with magnesium biotinate. Magnesium biotinate, compared with a commercial d-biotin, is more effective in reducing serum lipid concentrations and regulating protein levels of lipid metabolism-related biomarkers.
AtıfScopus5WoS5OpenAlex5İncele
